Fluoromacrolides Having Immunosuppressive Activity

1. A compound of Formula I: ##STR196## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 and R.sup.2 are independently selected from: 1) --N.sub.3 ; 2) --NHCN; 3) --NR.sup.6 R.sup.7, wherein R.sup.6 and R.sup.7 independently, are a) hydrogen, b) C.sub.1-12 alkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are independently selected from the group consisting of: i) hydrogen, ii) --OH, iii) C.sub.1-6 alkoxy, iv) --O--CO--C.sub.1-6 alkyl, v) --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are independently, hydrogen, or C.sub.1--6 alkyl, unsubstituted or substituted with phenyl vi) --CONR.sup.10 R.sup.11, vii) --CO.sub.2 H, viii) --CO--O--C.sub.1-6 alkyl, ix) --S--C.sub.1-6 alkyl, x) --SO--C.sub.1-6 alkyl, xi) --SO.sub.2 --C.sub.1-6 alkyl, xii) halo, xiii) --C.sub.3-7 -cycloalkyl, xiv) phenyl, unsubstituted or substituted with X, Y and Z, xv) naphthyl, unsubstituted or substituted with X, Y and Z, xvi) --CF.sub.3, c) C.sub.3-12 -alkenyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above, d) C.sub.3-7 cycloalkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above, e) phenyl, unsubstituted or substituted with X, Y and Z, f) naphthyl, unsubstituted or substituted with X, Y and Z, g) --SO.sub.2 -phenyl, wherein phenyl is unsubstituted or substituted with X, Y and Z, h) --SO.sub.2 --C.sub.1-6 alkyl, i) or where R.sup.6 and R.sup.7 and the N to which they are attached may form a heterocyclic ring selected from the group consisting of: morpholine, thiomorpholine, piperidine, and piperazine, and where the substituent(s), attached to the carbon atom(s) in the heterocyclic ring is/are independently selected from the group consisting of: i) hydrogen, ii) --OH, iii) C.sub.1-6 alkoxy, iv) --O--CO--C.sub.1-6 alkyl, v) --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, vi) --CONR.sup.10 R.sup.11, vii) --CO.sub.2 H, viii) --CO--O--C.sub.1-6 alkyl, ix) --SH, x) halo, xi) phenyl, unsubstituted or substituted with X, Y and Z, xii) naphthyl, unsubstituted or substituted with X, Y and Z, xiii) --CF.sub.3 ; 4) --N(R.sup.6)CO--O--R.sup.12, wherein R.sup.6 is as defined above and R.sup.12 is C.sub.1-12 alkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above; 5) --N(R.sup.6)CO--R.sup.13, wherein R.sup.6 is as defined above and R.sup.13 is a) hydrogen, b) C.sub.1-12 alkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above, c) C.sub.3-12 cycloalkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above, d) phenyl, unsubstituted or substituted with X, Y and Z, e) naphthyl, unsubstituted or substituted with X, Y and Z, or f) where R.sup.6 and R.sup.13 and the --NCO-- to which they are attached may form an unsubstituted or substituted 5- to 7-membered heterocyclic ring which may include one or two additional heteroatoms independently selected from the group consisting of O, S, or NR.sup.10, wherein R.sup.10 is as defined above; 6) --N(R.sup.14)COCH(R.sup.22)NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 are as defined above, R.sup.14 is selected from the definitions of R.sup.6, and R.sup.22 is a) hydrogen, b) C.sub.1-4 alkyl, unsubstituted or substituted with R.sup.23, wherein R.sup.23 is selected from the group consisting of: i) --OH, ii) C.sub.1-6 alkoxy, iii) --O--CO--C.sub.1-6 alkyl, iv) --SH, v) --S--C.sub.1-6 alkyl, vi) --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, vii) --CO.sub.2 H, viii) --CONH.sub.2, ix) imidazolyl, x) indolyl, xi) phenyl, and xii) p-hydroxyphenyl, or c) phenyl; 7) --N(R.sup.14)CO(CH.sub.2).sub.m NR.sup.6 R.sup.7, wherein m is 0 or 2-6, R.sup.6 and R.sup.7 are as defined above, and R.sup.14 is selected from the definitions of R.sup.6, or where R.sup.14 and R.sup.6 and the --NCO(CH.sub.2).sub.m N-- to which they are attached may form an unsubstituted or substituted 5- to 7-membered heterocyclic ring; 8) --N.dbd.C(R.sup.14)--NR.sup.6 R.sup.7, wherein R.sup.6 and R.sup.7 are as defined above, and R.sup.14 is selected from the definitions of R.sup.6, and wherein if either R.sup.6 or R.sup.7 are hydrogen, the tautomeric structure --NHC(R.sup.14).dbd.NR.sup.6 or 7 is also possible; 9) --N(R.sup.15).sub.3 +A.sup.-, wherein R.sup.15 is C.sub.1-6 alkyl, unsubstituted or substituted with phenyl or naphthyl, and wherein A.sup.- is a counterion selected from the group consisting of: acetate, adipate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, ethanesulfonate, fumarate, hemisulfate, hemitartrate, heptaonate, hexanoate, chloride, bromide, iodide, methanesulfonate, lactate, maleate, methanesulfonate 2-naphthalenesulfonate, nitrate, oxalate, pamoate, perchlorate, persulfate, picrate, pivalate, propionate, succinate, tartrate, tosylate, and undecanoate; and 10) ##STR197## wherein R.sup.16 and R.sup.17 are independently, a) hydrogen, b) phenyl, unsubstituted or substituted with X, Y and Z, c) naphthyl, unsubstituted or substituted with X, Y and Z, d) --CN, e) --CF.sub.3, f) --CO--C.sub.1-6 alkyl, or g) --CO--O--C.sub.1-6 alkyl; 11) C.sub.1-10 alkoxy; 12) substituted C.sub.1-10 alkoxy in which one or more substituent(s) is(are) selected from: a) hydroxy, b) C.sub.1-6 alkoxy, c) phenyl C.sub.1-3 alkoxy, d) substituted phenyl C.sub.1-3 alkoxy, in which the substituents on phenyl are X, Y and Z, e) --OCOC.sub.1-6 alkyl, f) --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, g) --NR.sup.6 COC.sub.1-6 alkyl, wherein R.sup.6 is as defined above, h) --COOR.sup.6, wherein R.sup.6 is as defined above, i) --CHO, j) phenyl, k) substituted phenyl in which the substituents are X, Y and Z, l) phenyloxy, m) substituted phenyloxy in which the substituents are X, Y and Z, n) 1- or 2-naphthyl, o) substituted 1- or 2-naphthyl in which the substituents are X, Y and Z, p) biphenyl, and q) substituted biphenyl in which the substituents are X, Y and Z; 13) C.sub.3-10 alkenyloxy; 14) substituted C.sub.3-10 alkenyloxy in which one or more substituent(s) is(are) selected from: a) hydroxy, b) C.sub.1-6 alkoxy, c) --OCO--C.sub.1-6 alkyl, d) C.sub.2-8 alkenyl, e) phenyl, f) substituted phenyl in which the substituents are X, Y and Z, g) 1- or 2-naphthyl, h) substituted 1- or 2-naphthyl in which the substituents are X, Y and Z, i) biphenyl, and j) substituted biphenyl in which the substituents are X, Y and Z; 15) C.sub.3-10 alkynyloxy; and 16) substituted C.sub.3-10 alkynyloxy in which one or more substituent(s) is(are) selected from: a) hydroxy, b) C.sub.1-6 alkoxy, c) --OCO--C.sub.1-6 alkyl, d) phenyl, e) substituted phenyl in which the substituents are X, Y and Z, f) 1- or 2-naphthyl, g) substituted 1- or 2-naphthyl in which the substituents are X, Y and Z, h) biphenyl, and i) substituted biphenyl in which the substituents are X, Y and Z; 17) phenyloxy; 18) substituted phenyloxy in which the substituents are X, Y and Z; 19) 1- or 2- naphthyloxy; 20) substituted 1- or 2-naphthyloxy in which the substituents are X, Y and Z; 21) biphenyloxy; 22) substituted biphenyloxy in which the substituents are X, Y and Z; and 23) hydroxy; or 24) where R.sup.1 and R.sup.2 may be both connected to form a 3- to 7-membered heterocyclic ring of the form; ##STR198## wherein p is zero or one, R.sup.6 is as defined above, and A is a) --CO--, b) --CS--, c) --CO--C.sub.1 -alkyl, d) --CS--C.sub.1 -alkyl, or e) --C.sub.1-2 --alkyl, wherein the alkyl may be unsubstituted or substituted with one or more of the following: i) --OH, ii) C.sub.1-6 alkyl, iii) C.sub.1-6 alkoxy, iv) --O--CO--C.sub.1-6 alkyl, v) --NR.sup.9 R.sup.10, wherein R.sup.9 and R.sup.10 are as defined above, vi) --CONR.sup.9 R.sup.10, vii) --CO.sub.2 H, viii) --CO--O--C.sub.1-6 alkyl, ix) --S--C.sub.1-6 alkyl, x) --SO--C.sub.1-6 alkyl, xi) --SO.sub.2 --C.sub.1-6 alkyl, xii) halo, xiii) phenyl, unsubstituted or substituted with X, Y or Z, or xiv) naphthyl unsubstituted or substituted with X, Y or Z; R.sup.3 is hydrogen, hydroxy, or C.sub.1-6 alkoxy; R.sup.4 is hydrogen, or R.sup.3 and R.sup.4 taken together form a double bond; R.sup.5 is methyl, ethyl, propyl or allyl; Q is F or OH, with the proviso that if Q is OH, R.sup.2 is other than OH or OCH.sub.3 ; W is O or (H, OH); X, Y and Z independently are selected from: a) hydrogen, b) C.sub.1-7 alkyl, c) C.sub.2-6 alkenyl, d) halo, such as Cl, Br, F or I, e) --(CH.sub.2).sub.t --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, and t is 0 or 2, f) --CN, g) --CHO, h) --CF.sub.3, i) --SR.sup.18, wherein R.sup.18 is hydrogen, C.sub.1-6 alkyl, or phenyl, j) --SOR.sup.18, wherein R.sup.18 is as defined above, k) --SO.sub.2 R.sup.18, wherein R.sup.18 is as defined above, l) --CONR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, m) R.sup.19 O(CH.sub.2)t--wherein R.sup.19 is hydrogen, C.sub.1-3 alkyl, hydroxy-C.sub.2-3 alkyl, phenyl or naphthyl and t is as defined above; n) --CH(OR.sup.20)(OR.sup.21), wherein R.sup.20 and R.sup.21 are C.sub.1-3 alkyl or taken together form an ethyl or propyl bridge, o) ##STR199## wherein R.sup.19 and t are as defined above; and p) ##STR200## wherein R.sup.19 and t are as defined above; or any two of X, Y and Z may be joined to form a saturated ring selected from dioxolanyl and dioxanyl; and n is 1 or 2.

2. A compound according to claim 1 wherein the steric configuration of formula I is as defined in formula III: ##STR201##

3. The compound according to claim 1 wherein: R.sup.1 and R.sup.2 are independently selected from: 1) --N.sub.3 ; 2) --NR.sup.6 R.sup.7, wherein R.sup.6 and R.sup.7 independently, are, a) hydrogen, b) C.sub.1-12 alkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are independently selected from the group consisting of: i) hydrogen, ii) --OH, iii) --O--CO--C.sub.1-6 alkyl, iv) --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are independently, hydrogen, or C.sub.1-6 alkyl, unsubstituted or substituted with phenyl v) --CONR.sup.10 R.sup.11, vi) --CO.sub.2 H, vii) --CO--O--C.sub.1-6 alkyl, and viii) phenyl, unsubstituted or substituted with X, Y and Z, c) C.sub.3-12 alkenyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above, d) or where R.sup.6 and R.sup.7 and the N to which they are attached may form a heterocyclic ring selected from: morpholine, thiomorpholine, piperidine, and piperizine, and where the substituent(s), attached to the carbon atoms(s) in the heterocyclic ring is/are independently selected from the group consisting of: i) hydrogen, ii) --OH, iii) --O--CO--C.sub.1-6 alkyl, iv) --CONR.sup.10 R.sup.11, v) --CO.sub.2 H, vi) --CO--O--C.sub.1-6 alkyl, and vii) phenyl, unsubstituted or substituted with X, Y and Z; 3) --N(R.sup.6)CO--O--R.sup.12, wherein R.sup.6 is as defined above and R.sup.12 is C.sub.1-12 alkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above; 4) --N(R.sup.6)CO--R.sup.13, wherein R.sup.6 is as defined above and R.sup.13 is a) hydrogen, b) C.sub.1-12 alkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above, c) C.sub.3-12 cycloalkyl, unsubstituted or substituted with R.sup.8 and R.sup.9, wherein R.sup.8 and R.sup.9 are as defined above, or d) phenyl, unsubstituted or substituted with X, Y and Z; 5) --N(R.sup.14)COCH(R.sup.22)NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 are as defined above, R.sup.14 is selected from the definitions of R.sup.6, and R.sup.22 is a) hydrogen, b) C.sub.1-4 alkyl, unsubstituted or substituted with R.sup.23, wherein R.sup.23 is selected from the group consisting of i) --OH, ii) C.sub.1-6 alkoxy, iii) --O--CO--C.sub.1-6 alkyl, iv) --SH, v) --S--C.sub.1-6 alkyl, vi) --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, vii) --CO.sub.2 H, viii) --CONH.sub.2, ix) imidazolyl, x) indolyl, xi) phenyl, and xii) p-hydroxyphenyl, or c) phenyl; 6) --N(R.sup.14)CO(CH.sub.2).sub.m NR.sup.6 R.sup.7, wherein m is 0 or 2-6, R.sup.6 and R.sup.7 are as defined above, and R.sup.14 is selected from the definitions of R.sup.6, or wherein R.sup.14 and R.sup.6 and the --NCO(CH.sub.2).sub.m N-- to which they are attached may form an unsubstituted or substituted 5- to 7-membered heterocyclic ring, such as 2-imidazolidone; 7) --N.dbd.C(R.sup.14)--NR.sup.6 R.sup.7, wherein R.sup.6 and R.sup.7 are as defined above, and R.sup.14 is selected from the definitions of R.sup.6, and wherein if either R.sup.6 or R.sup.7 are hydrogen, the tautomeric structure --NHC(R.sup.14).dbd.NR.sup.6or7 is also possible; 8) --N(R.sup.15).sub.3.sup.+ A.sup.-, wherein R.sup.15 is C.sub.1-6 alkyl, unsubstituted or substituted with phenyl or naphthyl, and wherein A.sup.- is a counterion selected from the group consisting of: acetate, adipate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, ethanesulfonate, fumarate, hemisulfate, hemitartrate, heptanoate, hexanoate, chloride, bromide, iodide, methanesulfonate, lactate, maleate, methanesulfonate, 2-naphthalene-sulfonate, nitrate, oxalate, pamoate, perchlorate, persulfate, picrate, pivalate, propionate, succinate, tartrate, tosylate, and undecanoate; and 9) ##STR202## wherein R.sup.16 and R.sup.17 are independently, a) hydrogen, b) phenyl, unsubstituted or substituted with X, Y and Z, c) naphthyl, unsubstituted or substituted with X, Y and Z, d) --CN, e) --CF.sub.3, f) --CO--C.sub.1-6 alkyl, or g) --CO--C.sub.1-6 alkyl; 10) C.sub.1-10 alkoxy; 11) substituted C.sub.1-10 alkoxy in which one or more substituent(s) is(are) selected from: a) hydroxy, b) C.sub.1-6 alkoxy, c) phenyl C.sub.1-3 alkoxy, d) substituted phenyl C.sub.1-3 alkoxy, in which the substituents on phenyl are X, Y and Z, e) --OCOC.sub.1-6 alkyl, f) --NR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, g) --NR.sup.6 CO--C.sub.1-6 alkyl, wherein R.sup.6 is as defined above, h) --COOR.sup.6, wherein R.sup.6 is as defined above, i) --CHO, j) phenyl, k) substituted phenyl in which the substituents are X, Y and Z, l) phenyloxy, and m) substituted phenyloxy in which the substituents are X, Y and Z; 12) C.sub.3-10 alkenyloxy; 13) substituted C.sub.3-10 alkenyloxy in which one or more substituent(s) is(are) selected from: a) hydroxy, b) C.sub.1-6 alkoxy, c) --OCO--C.sub.1-6 alkyl, d) C.sub.2-8 alkenyl, e) phenyl, and f) substituted phenyl in which the substituents are X, Y and Z; 14) C.sub.3-10 alkynyloxy; 15) substituted C.sub.3-10 alkynyloxy in which one or more substituent(s) is(are) selected from: a) hydroxy, b) C.sub.1-6 alkoxy, c) --OCO--C.sub.1-6 alkyl, d) phenyl, and e) substituted phenyl in which the substituents are X, Y and Z; 16) phenyloxy; 17) substituted phenyloxy in which the substituents are X, Y and Z; 18) 1- or 2-naphtyloxy; 19) substituted 1- or 2-naphthyloxy in which the substituents are X, Y and Z; and 20) hydroxy; or 21) wherein R.sup.1 and R.sup.2 may both connected to form a 3- to 7-membered heterocyclic ring of the form: ##STR203## wherein p is one, R.sup.6 is as defined above, and A is a) --CO--, b) --CO--C.sub.1 -alkyl, or c) C.sub.1-2 -alkyl; R.sup.3 is hydrogen or hydroxy; R.sup.4 is hydrogen; R.sup.5 is ethyl, propyl or allyl; Q is F or OH, with the proviso that if Q is OH, R.sup.2 is other than OH or OCH.sub.3 ; W is O or (H, OH); X, Y and Z independently are selected from: a) hydrogen, b) C.sub.1-7 alkyl, c) C.sub.2-6 alkenyl, d) halo, such as Cl, Br, F or I, e) --CHO, f) --CONR.sup.10 R.sup.11, wherein R.sup.10 and R.sup.11 are as defined above, g) R.sup.19 O(CH.sub.2).sub.t -- wherein R.sup.19 is hydrogen, C.sub.1-3 alkyl, hydroxy-C.sub.2-3 alkyl, phenyl or naphthyl and t is 0 to 2; h) --CH(OR.sup.20)(OR.sup.21), wherein R.sup.20 and R.sup.21 are C.sub.1-3 alkyl or taken together form an ethyl or propyl bridge, i) ##STR204## wherein R.sup.19 and t are as defined above; and j) ##STR205## wherein R.sup.19 and t are as defined above; or any two of X, Y and Z may be joined to form a saturated ring selected from dioxolanyl or dioxanyl; and n is 1 or 2, or a pharmaceutically acceptable salt thereof.

4. A compound which is selected from the group consisting of: 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-me thylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricycl o[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-teteeone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-me thylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricycl o[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3",4"-dihydroxy-cyclohexyl)-23,25-dime thoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-dihydroxy-12-[2'-(3",4"-dihydroxy-cyclohexyl)-23,25-di methoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-azido-3"-methoxycyclohexyl)-1'-meth ylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[ 22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-meth ylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[ 22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-azido-3"-methoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-methoxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-N-(2-propenyl)-amino-3"-methox ycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-N-methylamino-3"-methoxycycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-methylamino-3"-methoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-1'"-adamantane-carboxamido-3"- methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl- 11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-cyclopropanecarboxamid-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-formamido-3"-methoxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-{2'-(4"-(4'",5'"-dicarboethoxy-1'",2'" ,3'"-triazole)-3"-methoxycyclohexyl)-1'-methylvinyl}-23,25-dimethoxy-13,19, 21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-acetylamino-3"-methoxy-cyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-hydroxy-cyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-amino-4"-hydroxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-azido-3"-methoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-methoxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-methoxycyclohexyl)-1'-meth ylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[ 22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1-hydroxy-12-[2'-(4"-acetylamino-3"-methoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-hydroxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-aminocyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-beta-amino-3"-methoxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-alpha-amino-3"-methoxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-beta-amino-3"-methoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-alpha-amino-3"-methoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-isopropyloxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-isopropyloxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-n-propyloxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-n-propyloxycyclohexyl)-1'- methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricy clo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'- methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricy clo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-ethoxycyclohexyl)-1'-methy lvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[2 2.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-methylcarbamate-3"-methoxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-benzylcarbamate-3"-methoxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-acetamidine-3"-methoxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-benzamidine-3"-methoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-formamidine-3"-methoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(L-phenylalanyl)-amido-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(L-phenylalanyl)amido-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2"-(4"-(D-phenylalanyl)-amido-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(D-phenylalanyl)amido-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2"-(4"-(aminoacetyl-amino)-3"-methoxy cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-d ioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(aminoacetylamino)-3"-methoxycycloh exyl)-4'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(2-hydroxypropyl-amino)-3"-met hoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11, 28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(2-hydroxypropylamino)-3"-methoxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(1-aza-4-oxabicyclo-[4.4.0]dec-6-y l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(1-aza-4-oxabicyclo[4.4.0]-dec-6-yl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-trimethylamino-3"methoxycycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone Iodide; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-isopropoxycyclohexyl) -1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azat ricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-isopropoxycyclohexyl)-1'-m ethylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyc lo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Propyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-propyloxycyclohexyl)-1'-m ethylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyc lo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-isopropoxycyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.31.0.sup.4,9 ]octacos-18-ene-2,3,20,26-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-[4"-(N'-t-butoxycarbonyl-D-phenyla lanine)amido-3"-n-propyloxycyclohexyl]-1'-methylvinyl]-23,25-dimethoxy-13,1 9,21,27-tetra-methyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-[4"-(N'-t-butoxycarbonyl-L-phenyla lanine)amido-3"-n-propyloxycyclohexyl]-1'-methylvinyl]-23,25-dimethoxy-13,1 9,21,27-tetra-methyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-acetoxyacetylamino-3"-ethoxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(1"'-adamantanecarboxamido)-3" -ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl- 11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-cyclopropanecarbox-amido-3"-is opropyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetrameth yl-11,28-dioxa-4-aza-tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2-(4"-formamido-3"-n-propyloxycyclohe xyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-{2'-[4"',5"'-dicarboeth-oxy-1"',2"',3" '-triazole)-3"-n-propyloxycyclohexyl]-1'-methyl-vinyl}-23,25-dimethoxy-13,1 9,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-ethoxycyclo-hexyl)-1'-meth ylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[ 22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-benzylamino-3"-isopropyloxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-trimethylamino-3"-ethoxycycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone-Iodide; 17-Ethyl-20-fluoro-1,2,14-trihydroxy-12-[2'-(4"-acetylamino-3"-n-propyloxyc yclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-di oxa-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-3,10,16-trione; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-{2'-[4"-(N'-phenylaminocarbonyl)amino- 3"-isopropyloxycyclohexy]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetra methyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-{2'-[4"-(ethoxycarbonyl)-amino-3"-n-pr opyloxycyclohexyl]-1'-methylvinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl- 11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3, 10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-acetylamino-3"-n-propyl-oxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo-[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-dimethylamino-3"-methoxycycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-dimethylamino-3"-methoxycyclohexyl) -1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azat ricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-benzylamino-3"-methoxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-benzylamino-3"-methoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-dimethylamino-3"-isopropyloxycycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-dimethylamino-3"-n-propyloxycyclohe xyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-benzylamino-3"-isopropyloxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-benzylamino-3"-n-propyloxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(2-phenyl-2-hydroxyethyl)amino-3"-m ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-1 1,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-morpholino-3"-methoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-morpholino-3"-methoxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-n-butyloxycyclo-hexyl)-1'- methylvinyl]-23,25-dimethoxy-1,3,19,21,27-tetramethyl-11,18-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-butyloxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(3-methylbutyloxy)cyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(3-methylbutyloxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(2-methylbutyloxy)cyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(2-methylbutyloxy)cyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(N-(2-methyl-3-(4-hydroxy-phenyl)pr openyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21 ,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(N-(2-methyl-3-(4-hydroxypheny l)propenyl)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,1 9,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(N-(3-(4-hydroxyphenyl)-propenyl)am ino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetra methyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(N-(3-(4-hydroxyphenyl)propeny l)amino-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-t etramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.3,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(N-3-phenylpropenyl)amino-3"-m ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-1 1,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(N-3-phenylpropenyl)-amino-3"-metho xycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(L-Trp)amido-3"-methoxycyclohexyl)- 1'-methoxyvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azat ricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-phenyloxy-3"-methoxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-phenyloxy-4"-hydroxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-phenyloxy-3"-hydroxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-fluorophenyloxy)-3"-metho xycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-chlorophenyloxy)-3"-metho xycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-methylphenyl-oxy)-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(4"'-methylphenyloxy)-4"-hydro xycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4.9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-methylphenyloxy)-3"-hydro xycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-phenoxyphenyloxy)-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-phenoxyphenyloxy)-3"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(4"'-phenoxyphenyloxy)-4"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(naphth-1-yloxy)-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(naphth-1-yloxy)-4"-hydroxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(naphth-1-yloxy)-3"-hydroxycyc lohexyl)-1"-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(naphth-2-yloxy)-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(naphth-2-yloxy)-3"-hydroxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-napth-2-yloxy)-4"-hydroxycyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(napth-2-yloxy)-3"-methoxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(6"'-methoxynaphth-2-yloxy)-3" -methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(6"'-methoxynaphth-2-yloxy)-4" -hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(6"'-methoxynaphth-2-yloxy)-3" -hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(4"'-methoxyphenyloxy)-4"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-methoxyphenyloxy)-3"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(3"'-methoxyphenyloxy)-4"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3"'-methoxyphenyloxy)-3"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(4"'-hydroxyphenyloxy)-4"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4"'-hydroxyphenyloxy)-3"-hydr oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(6"'-hydroxynaphth-2-yloxy)-3" -hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-(6"'-hydroxynaphth-2-yloxy)-4" -hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3'",4'"-dichlorophenyloxy)-3" -methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo]22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(phenanthr-9-yl)-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3'",4'"-methylenedioxyphenylo xy)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetra methyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(2'",3'"-dihydrobenzofuran-5-y l)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetram ethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(naphth-2-yl)-3"-methoxycycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(1'",4'"-benzodioxane-6-yl)-3" -methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,2,14-trihydroxy-12-[2'-(4"-(naphth-2-yl)-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-3,10,16-trione; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-allyloxy-3"-methoxycyclohexyl) -1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(2-butynyloxy)-3"-methoxycyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-cinnamyloxy-3"-methoxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-methoxy-4"-phenylpropyloxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-allyloxy-3"-hydroxycyclohexyl) -1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azat ricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-allyloxy-4"-hydroxycyclohexyl) -1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azat ricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-hydroxy-4"-isopropyloxycyclohe xyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-isopropyloxycyclohe xyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-sec-butenyloxy-3"-hydroxycyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-sec-butenyloxy-4"-hydroxycyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-trans-2-butenyloxy)-3"-hydroxy cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-d ioxa-4-azatricyclo]22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-trans-2-butenyloxy)-4"-hydroxy cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-d ioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetrane; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-hydroxy-4"-(3-methyl-2-butenyl oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-(3-methyl-2-butenyl oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,29,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-hydroxy-4"-(2-methylpropyloxyc yclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-di oxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-(2-methylpropenylox ycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-cinnamyloxy-3"-hydroxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-cinnamyloxy-4"-hydroxycyclohex yl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-a zatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-sec-butenyloxy-3"-hydroxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-sec-butenyloxy-4"-hydroxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo-[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-cinnamyloxy-3"-methoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-methoxy-4"-phenylpropyloxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4'"-methoxyphenyloxy)-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3'"-methoxyphenyloxy)-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(6'"-hydroxynaphth-2-yloxy)-3" -methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4'"-hydroxyphenyloxy)-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4'"-methylthiophenyloxy)-3"-m ethoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,29,21,27-tetramethyl-1 1,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(2'"-methylphenyloxy)-3"-metho xycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,29,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3'"-methylphenyloxy)-3"-metho xycyclohexyl-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3'",4'"-dimethylphenyloxy)-3" -methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl -11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-allyloxy-3"-methoxycyclohexyl)-1'-m ethylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyc lo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(2-butynyloxy)-3"-methoxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20fluoro-1-hydroxy-12-[2'-(4"-cinnamyloxy-3"-methoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-methoxy-4"-phenylpropyloxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-allyloxy-3"-hydroxycyclohexyl)-1'-m ethylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyc lo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-allyloxy-4"-hydroxycyclohexyl)-1'-m ethylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyc lo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-hydroxy-4"-isopropyloxycyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy 13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-hydroxy-3"-isopropyloxycyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo[22.3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(trans-2-butenyloxy)-3"-hydroxycycl ohexyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-(trans-2-butenyloxy)-4"-hydroxycycl ohexyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-hydroxy-4"-(3-methyl-2-butenyloxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-hydroxy-3"-(3-methyl-2-butenyloxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-hydroxy-4"-(2-methylpropenyloxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-hydroxy-3"-(2-methylpropenyloxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3"-cinnamyloxy-4"-hydroxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-sec-phenethyloxy-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-12,28-diox a-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(2-methylcinnamyloxy)-3"-metho xycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4-methyl-2,4-hexadienyloxy)-3 "-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethy l-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(p-methoxycinnamyloxy)-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3'", 4'"-methylenedioxycinnamyloxy)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25 -dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4 ,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(4,4-dimethyl-2-trans-pentenyl oxy)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetr amethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,4-dihydroxy-12-[2'-(4"-(3-cyclohexyl-2-trans-propenylo xy)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetra methyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-p-fluorocinnamyloxy-3"-methoxy cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-d ioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-chlorocinnamyloxy-3"-methoxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-p-bromocinnamyloxy-3"-methoxyc yclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-di oxa-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(3"-methoxy-4"-p-fluorophenylpropy loxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11, 28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3",4"-diallyloxycyclohexyl)-1'-methylv inyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22. 3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(3",4"-dipropyloxycyclohexyl)-1'-methyl vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22 .3.1.0.sup.4,9 ]-octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(2-benzylamino)-ethoxy-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetra-one; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(2-benzylamino)-ethoxy-3"-methoxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo-[22.3.1.04,9]octacos-18-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(2-benzyloxyethoxy)-3"-methoxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-benzyloxymethoxy-3"-methoxycyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(naphth-2-yloxy)-3"-allyloxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(ethoxycarbomethoxy)-3"-methox ycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(p-hydroxycinnamyl)oxy-3"-meth oxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,2 8-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(p-hydroxycinnamyl)oxy-3"-methoxycy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(3'",5'"-difluorocinnamyl)oxy- 3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetrameth yl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(3'",5'"-difluorocinnamyl)oxy-3"-me thoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11 ,28-dioxa-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-phenoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-phenoxycyclohexyl)-1'-meth ylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[ 22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-phenoxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-phenoxycyclohexyl-1'-methy lvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[2 2.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-phenoxy-3"-aminocyclohexyl)-1'-meth ylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[ 22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-dimethylamino-3"-phenoxycyclohexyl) -1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azat ricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-methoxyphenoxy)cycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-hydroxyphenoxy)cycloh exyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-acetylamino-3"-phenoxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-fluorophenoxy)cyclohe xyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(4'"-carboxyphenoxy)c yclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-di oxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-trifluoromethylphenox ycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(3'",4'"-dimethoxyphenoxyc yclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-di oxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(4'"-methoxyphenoxy)c yclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-di oxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-methylphenoxy)cyclohe xyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(4'"-methylphenoxy)cy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(3'"-methoxyphenoxy)cycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(3'"-hydroxyphenoxy)cycloh exyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4 -azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-N-(2-propenyl) amino-3"-phenoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-te tramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-(acetylamino-3"-(4'"-methoxyphenoxy )cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-allyloxycyclohexyl)-1 '-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatri cyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-allyloxycyclohexyl)-1'-met hylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo [22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-allyloxy-3"-aminocyclohexyl)-1'-met hylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo [22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-cinnamyloxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"amino-3"-cinnamyloxycyclohexyl)-1'-m ethylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyc lo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-cinnamyloxycyclohexyl )-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza tricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(3"'-phenylpropyloxy) cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-d ioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(3"'-phenylpropyloxy)cyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(2'"-benzyloxyethoxy) -cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(2'"-benzyloxyethoxy)cyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(4'"-hydroxycinnamylo xy)cyclohexyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-hydroxycinnamyloxy)cy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(4'"-hydroxycinnamylo xy)cyclohexyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Allyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-hydroxycinnamyloxy)cy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-acetylamino-3"-allyloxycyclohe xyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-acetylamino-3"-allyloxycyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-N-(2-propenyl)amino-3"-allyloxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(L-phenylalanine)-amido-3"-all yloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11 ,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(D-phenylalanine)-amido-3"-all yloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11 ,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-cyclopropanecarboxamido-3"-allyloxy cyclohexyl)-1'-methylvinyl]23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-di oxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-formamido-3"-allyloxycyclohexyl)-1' -methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatric yclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"(4'",5'"-dicarboethoxy-1'",2'", 3'"-triazole)-3"-allyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19, 21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-benzylamino-3"-allyloxycyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-dimethylamino-3"-allyl-oxycyclohexy l)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-az atricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-trimethylamino-3"-allyloxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone iodide; 17-Ethyl-20-fluoro-1,2,14-trihydroxy-12-[2'-(4"-acetylamino-3"-allyloxycycl ohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa -4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-trione; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(N-phenyl aminocarbonyl)amino-3"-allyloxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy -13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-(ethoxycarbonyl)-amino-3"-ally loxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11, 28-dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-sec-butenyloxycyclohe xyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-sec-butenyloxycyclohexyl)- 1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatr icyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(3-methyl-2-butenylox y)cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28 -dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(3-methyl-2-butenyloxy)cyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1,14-dihydroxy-12-[2'-(4"-amino-3"-(2-methyl-propenyloxy )cyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28- dioxa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(2-methylpropenyloxy)cyclo hexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa- 4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-methoxycinnamyloxy)cy clohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dio xa-4-azatricyclo[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(4'"-fluorocinnamyloxy)cyc lohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-diox a-4-azatricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; and 17-Ethyl-20-fluoro-1-hydroxy-12-[2'-(4"-amino-3"-(2-butynyloxy)-cyclohexyl) -1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azat ricyclo-[22.3.1.0.sup.4,9 ]octacos-18-ene-2,3,10,16-tetraone; or a pharmaceutically acceptable salt thereof.

5. A compound of claim 4 which is: ##STR206##

6. A compound of claim 4 which is: ##STR207##

7. A compound of claim 4 which is: ##STR208##

8. A compound of claim 4 which is: ##STR209##

9. A compound of claim 4 which is: ##STR210##

10. A compound of claim 4 which is: ##STR211##

11. A pharmaceutical composition for the treatment of immunoregulatory disorders or diseases comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

12. A pharmaceutical composition for the treatment of resistance to transplantation comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

13. A pharmaceutical composition for the topical treatment of inflammatory and hyperproliferative skin diseases and or cutaneous manifestations of immunologically-mediated illnesses comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

14. A pharmaceutical composition for the treatment of reversible obstructive airways disease comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

15. A pharmaceutical composition for the treatment of male pattern alopecia or alopecia senilis a comprising a pharmaceutical carrier and a therapeutically effective amount of the compound of claim 1.

16. A method for the treatment of immunoregulatory disorders or diseases comprising the administration to a mammalian species in need of such treatment an effective amount of the compound of claim 1.

17. A method for the treatment of resistance to transplantation comprising the administration to a mammalian species in need of such treatment an effective amount of the compound of claim 1.

18. A method for the topical treatment of inflammatory and hyperproliferative skin diseases and or cutaneous manifestations of immunologically-mediated illnesses comprising the administration to a mammalian species in need of such treatment of an effective amount of the compound of claim 1.

19. A method for the treatment of reversible obstructive airways disease comprising the administration to a mammalian species in need of such treatment of an effective amount of the compound of claim 1.

20. A method for revitalizing hair comprising the administration to a mammalian species in need of such treatment of an effective amount of the compound of claim 1.

21. A method for the treatment of male pattern alopecia or alopecia senilis comprising the administration to a mammalian species in need of such treatment of an effective amount of the compound of claim 1.