(9aS,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-allyl-24-[[tert-butyl(dimethyl)silyl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-14-hydroxy-23,25-dimethoxy-2,2,13,19,21,27-hexamethyl-7,8,9,9a,12,13,14,15,20,21,22,23,24,25,26,27-hexadecahydro-4H-[1,3]dioxolo[4,5-f]pyrido[2,1-c][1,4]oxazacyclotricosine-4,10,16(6H,17H)-trione -Drug Synthesis Database

【结构式】

【分子编号】17385

【品名】(9aS,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-allyl-24-[[tert-butyl(dimethyl)silyl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-14-hydroxy-23,25-dimethoxy-2,2,13,19,21,27-hexamethyl-7,8,9,9a,12,13,14,15,20,21,22,23,24,25,26,27-hexadecahydro-4H-[1,3]dioxolo[4,5-f]pyrido[2,1-c][1,4]oxazacyclotricosine-4,10,16(6H,17H)-trione

【CA登记号】

【分子式】C₆₉H₁₀₇NO₁₂Si₂

【分子量】1198.77912

【元素组成】C 69.13% H 9% N 1.17% O 16.02% Si 4.69%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XVII)

Ester (XIII) was submitted to cyclization by means of triethylsilyl triflate and 2-chloro-1-methylpyridinium iodide (MCPI) in dichloromethane/methanol gaving the macrocyclic compound (XIV). Elimination of the p-methoxybenzyl group of (XIV) with dichlorodicyanobenzoquinone (DDQ) in dichloromethane yielded the alcohol (XV), which was converted into the iodo derivative (XVI) with I2, triphenylphosphine and imidazole in hot toluene. The reductive fragmentation of the spiroketal rings of (XVI) with zinc/silver-graphite in THF afforded compound (XVII) with the adequate configuration in the C21-C24 fragment.

参考文献中间体

合成目标

【1】 Liu, L.B.; Roper, T.D.; Gleason, J.L.; Ireland, R.E.; Total synthesis of FK-506. 2. Completion of the synthesis. Tetrahedron 1997, 53, 39, 13257.
【2】 Liu, L.B.; Roper, T.D.; Ireland, R.E.; Total synthesis of FK-506. 1. Construction of the C16-C34 fragment. Tetrahedron 1997, 53, 39, 13221.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIII)	17381	5-((1R,3S,4R,5S,7S,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-10-[4-((1R,2S,3E)-4-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1,3-dimethyl-2-[[(2S)piperidinylcarbonyl]oxy]-3-butenyl)-9-[(4-methoxybenzyl)oxy]-2,2-dimethyl-1,3,7-trioxaspiro[5.5]undec-11-yl]-3,5-dimethoxy-1,7,9-trimethyl-9-decenyl)-2,2-dimethyl-1,3-dioxole-4-carboxylic acid	C₈₀H₁₂₃NO₁₆Si₂	详情	详情
(XIV)	17382	(10S,12S,13R,14S,16R,28S,31S,32R)-13-[[tert-butyl(dimethyl)silyl]oxy]-31-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-12,14-dimethoxy-4-[(4-methoxybenzyl)oxy]-8,10,16,19,19,32,35,35-octamethyl-2,18,20,30,34,36-hexaoxa-23-azapentacyclo[31.3.1.0(1,6).0(17,21).0(23,28)]heptatriaconta-7,17(21)-diene-22,29-dione	C₈₀H₁₂₁NO₁₅Si₂	详情	详情
(XV)	17383	(10S,12S,13R,14S,16R,28S,31S,32R)-13-[[tert-butyl(dimethyl)silyl]oxy]-31-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-4-hydroxy-12,14-dimethoxy-8,10,16,19,19,32,35,35-octamethyl-2,18,20,30,34,36-hexaoxa-23-azapentacyclo[31.3.1.0(1,6).0(17,21).0(23,28)]heptatriaconta-7,17(21)-diene-22,29-dione	C₇₂H₁₁₃NO₁₄Si₂	详情	详情
(XVI)	17384	(10S,12S,13R,14S,16R,28S,31S,32R)-13-[[tert-butyl(dimethyl)silyl]oxy]-31-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-4-iodo-12,14-dimethoxy-8,10,16,19,19,32,35,35-octamethyl-2,18,20,30,34,36-hexaoxa-23-azapentacyclo[31.3.1.0(1,6).0(17,21).0(23,28)]heptatriaconta-7,17(21)-diene-22,29-dione	C₇₂H₁₁₂INO₁₃Si₂	详情	详情
(XVII)	17385	(9aS,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-allyl-24-[[tert-butyl(dimethyl)silyl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-14-hydroxy-23,25-dimethoxy-2,2,13,19,21,27-hexamethyl-7,8,9,9a,12,13,14,15,20,21,22,23,24,25,26,27-hexadecahydro-4H-[1,3]dioxolo[4,5-f]pyrido[2,1-c][1,4]oxazacyclotricosine-4,10,16(6H,17H)-trione	C₆₉H₁₀₇NO₁₂Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVII)

The 1,3-dioxole ring of (XVII) was cleaved by selective oxidation with dimethyldioxirane (DMD) in acetone giving the tricarbonyl compound (XVIII) (silylated FK-506), which was finally desilylated by means of HF in acetonitrile/ water. 2) Aldehyde (VI) was prepared according to a previously reported method (Ireland, R.E. et al. J Org Chem 1992, 57: 5071).

参考文献中间体

合成目标

【1】 Liu, L.B.; Roper, T.D.; Ireland, R.E.; Total synthesis of FK-506. 1. Construction of the C16-C34 fragment. Tetrahedron 1997, 53, 39, 13221.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVII)	17385	(9aS,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-allyl-24-[[tert-butyl(dimethyl)silyl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-14-hydroxy-23,25-dimethoxy-2,2,13,19,21,27-hexamethyl-7,8,9,9a,12,13,14,15,20,21,22,23,24,25,26,27-hexadecahydro-4H-[1,3]dioxolo[4,5-f]pyrido[2,1-c][1,4]oxazacyclotricosine-4,10,16(6H,17H)-trione		C₆₉H₁₀₇NO₁₂Si₂	详情	详情
(XVIII)	17386	(3S,4R,5S,8R,12S,14S,15R,16S,18R,26aS)-8-allyl-15-[[tert-butyl(dimethyl)silyl]oxy]-3-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-5-hydroxy-14,16-dimethoxy-4,10,12,18-tetramethyl-5,6,11,12,13,14,15,16,17,18,24,25,26,26a-tetradecahydro-3H-pyrido[2,1-c][1,4]oxazacyclotricosine-1,7,19,20,21(4H,8H,23H)-pentone		C₆₆H₁₀₁NO₁₂Si₂	详情	详情

Extended Information