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【结 构 式】

【药物名称】Ascomycin, Immunomycin, L-683590, FK-520, FR-900520

【化学名称】[1R,9S,12S(1'R,3'R,4'R),13R,14S,17R,21S,23S,24R,25S,27R]-17-Ethyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1(E)-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18(E)-ene-2,3,10,16-tetraone
　　　　　　[3S(1'R,3'R,4'R),4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS]-15,19-Epoxy-8-ethyl-5,19-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1(E)-methylvinyl]-14,16-dimethoxy-4,10,12,18-tetramethyl-1,4,5,6,7,8,11,12,13,14,15,16,17,18,19,20,21,23,24,25,26,26a-docosahydro-3H-pyrido[2,1-c][1,4]oxaazacyclotricosine-1,7,20,21-tetraone

【CA登记号】104987-12-4

【 分 子 式 】C43H69NO12

【 分 子 量 】792.02888

【开发单位】Fujisawa (Originator)

【药理作用】IMMUNOMODULATING AGENTS, Immunosuppressants

合成路线1合成路线2

合成路线1

The reaction of ascomycin (I) with Tbdms-Cl and imidazole gives the bis silylated compound (II), which is regioselectively monodesilylated by means of aq. HF in acetonitrile to yield the monosilylated compound (III). The silylation of (III) with 2-bromophenyldimethylsilyl chloride (IV) and imidazole affords the new disilylated compound (V), which is submitted to radical translocating/reducing conditions by means of Et3N/O2 as radical initiator and Bu3Sn2H as deuterium source. Under these conditions a mixture of labeled compounds (VI) and (VII) is obtained where about 70% is the ascomycin labeled compound (VI) and 30% the aromatic labeled compound (VII).

参考文献 中间体
【1】 Acemoglu, M.; et al.; Regio- and stereoselective preparation of ascomycin-d1 and FK 506-d1. J Label Compd Radiopharm 2002, 45, 5, 361.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI),(VII) 55705 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone C57H93NO12Si2 详情 详情
(I) 14951 (1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetron C43H69NO12 详情 详情
(II) 22753 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-[[tert-butyl(dimethyl)silyl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone C55H97NO12Si2 详情 详情
(III) 22754 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-[[tert-butyl(dimethyl)silyl]oxy]-17-ethyl-1-hydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone C49H83NO12Si 详情 详情
(IV) 55699 (2-bromophenyl)(chloro)dimethylsilane C8H10BrClSi 详情 详情
(V) 55704 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-12-[(E)-2-((1R,3R,4R)-4-{[(2-bromophenyl)(dimethyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-14-{[tert-butyl(dimethyl)silyl]oxy}-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone C57H92BrNO12Si2 详情 详情
(VI) 55706 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone C57H93NO12Si2 详情 详情
(VII) 55707 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone C57H93NO12Si2 详情 详情

合成路线2

This mixture is desilylated by means of aq. HOAc in THF to yield a 53:47 mixture of labeled and unlabeled ascomycin.

参考文献 中间体
【1】 Acemoglu, M.; et al.; Regio- and stereoselective preparation of ascomycin-d1 and FK 506-d1. J Label Compd Radiopharm 2002, 45, 5, 361.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI),(VII) 55705 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone C57H93NO12Si2 详情 详情
(I) 14951 (1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetron C43H69NO12 详情 详情
(VI) 55706 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone C57H93NO12Si2 详情 详情
(VII) 55707 (1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone C57H93NO12Si2 详情 详情
Extended Information