(1E,3S,4R,5S,7R,8R,9E,12S,14S,15R,16S,18R)-8-allyl-7,15-bis{[tert-butyl(dimethyl)silyl]oxy}-14,16,19,19-tetramethoxy-1-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2,4,10,12,18-pentamethyl-1,9-nonadecadiene-3,5-diol -Drug Synthesis Database

【结构式】

【分子编号】57362

【品名】(1E,3S,4R,5S,7R,8R,9E,12S,14S,15R,16S,18R)-8-allyl-7,15-bis{[tert-butyl(dimethyl)silyl]oxy}-14,16,19,19-tetramethoxy-1-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2,4,10,12,18-pentamethyl-1,9-nonadecadiene-3,5-diol

【CA登记号】

【分子式】C₅₉H₁₁₈O₁₀Si₃

【分子量】1071.83642

【元素组成】C 66.12% H 11.1% O 14.93% Si 7.86%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XLIV)

The condensation of (XL) with the intermediate 14-iodo-10-tetradecenal dimethylacetal (XXI) by means of BuLi in THF/HMPA gives the adduct (XLI), which is desulfurized by means of NCS and AgNO3 in acetone/THF/water to yield the ketonic product (XLII). The cleavage of the 4-methoxybenzyl group of (XLII) by means of DDQ in dichloromethane affords the beta-hydroxyketone (XLIII). The reduction of the ketonic group of (XLIII) with LiAlH4 and LiI in ethyl ether provides the dihydroxy compound (XLIV), which is selectively monoprotected with Tips-OTf and 2,6-lutidine in dichloromethane to give the intermediate (XLV).

参考文献中间体

合成目标

【1】 Smith, A.B. III; et al.; Formal total synthesis of FK506. Concise construction of the C(10)-C(34) segment via an effective coupling tactic. Tetrahedron Lett 1994, 35, 25, 4271.
【2】 Chen, K.; Formal total synthesis of (-)-FK506. Diss Abstr Int B - Sci Eng 1993, 53, 9, 4663.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXI)	57344	(1S,2R,3E,6S,8S,9R,10S,12R)-2-allyl-9-{[tert-butyl(dimethyl)silyl]oxy}-1-(iodomethyl)-8,10,13,13-tetramethoxy-4,6,12-trimethyl-3-tridecenyl tert-butyl(dimethyl)silyl ether; (5S,6R,7E,10S,12S,13R)-6-allyl-5-(iodomethyl)-12-methoxy-2,2,3,3,8,10,15,15,16,16-decamethyl-13-[(1S,3R)-1,4,4-trimethoxy-3-methylbutyl]-4,14-dioxa-3,15-disila-7-heptadecene	C₃₆H₇₃IO₆Si₂	详情	详情
(XL)	57356	[((1R,2R,4R)-4-{(E,3S,4S)-4-(1,3-dithian-2-yl)-3-[(4-methoxybenzyl)oxy]-2-methyl-1-pentenyl}-2-methoxycyclohexyl)oxy](triisopropyl)silane; (1S,2E)-1-[(1S)-1-(1,3-dithian-2-yl)ethyl]-3-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2-methyl-2-propenyl 4-methoxybenzyl ether	C₃₄H₅₈O₄S₂Si	详情	详情
(XLI)	57359	4-{[((1S,2E)-1-{(1S)-1-[2-((2R,3R,4E,7S,9S,10R,11S,13R)-3-allyl-2,10-bis{[tert-butyl(dimethyl)silyl]oxy}-9,11,14,14-tetramethoxy-5,7,13-trimethyl-4-tetradecenyl)-1,3-dithian-2-yl]ethyl}-3-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2-methyl-2-propenyl)oxy]methyl}phenyl methyl ether	C₇₀H₁₃₀O₁₀S₂Si₃	详情	详情
(XLII)	57360	(1E,3S,4S,7R,8R,9E,12S,14S,15R,16S,18R)-8-allyl-7,15-bis{[tert-butyl(dimethyl)silyl]oxy}-14,16,19,19-tetramethoxy-3-[(4-methoxybenzyl)oxy]-1-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2,4,10,12,18-pentamethyl-1,9-nonadecadien-5-one	C₆₇H₁₂₄O₁₁Si₃	详情	详情
(XLIII)	57361	(1E,3S,4S,7R,8R,9E,12S,14S,15R,16S,18R)-8-allyl-7,15-bis{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-14,16,19,19-tetramethoxy-1-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2,4,10,12,18-pentamethyl-1,9-nonadecadien-5-one	C₅₉H₁₁₆O₁₀Si₃	详情	详情
(XLIV)	57362	(1E,3S,4R,5S,7R,8R,9E,12S,14S,15R,16S,18R)-8-allyl-7,15-bis{[tert-butyl(dimethyl)silyl]oxy}-14,16,19,19-tetramethoxy-1-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2,4,10,12,18-pentamethyl-1,9-nonadecadiene-3,5-diol	C₅₉H₁₁₈O₁₀Si₃	详情	详情
(XLV)	57363	(1E,3S,4S,5S,7R,8R,9E,12S,14S,15R,16S,18R)-8-allyl-7,15-bis{[tert-butyl(dimethyl)silyl]oxy}-14,16,19,19-tetramethoxy-1-{(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl}-2,4,10,12,18-pentamethyl-5-[(triisopropylsilyl)oxy]-1,9-nonadecadien-3-ol	C₆₈H₁₃₈O₁₀Si₄	详情	详情

Extended Information