(5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one -Drug Synthesis Database

【结构式】

【分子编号】53699

【品名】(5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one

【CA登记号】n/a

【分子式】C₃₃H₆₀O₃Si

【分子量】532.9231

【元素组成】C 74.38% H 11.35% O 9.01% Si 5.27%

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：(XIII)

Allylic oxidation of (VIII) by means of t-butyl hydroperoxide and chromium hexacarbonyl produced enone (IX). Subsequent Birch reduction of (IX) employing lithium metal in liquid ammonia gave the saturated ketone (X), which was further reduced to alcohol (XI) with K-Selectride in cold THF. Removal of the acetate ester of (XI) was achieved by treatment with NaCN in MeOH, giving diol (XII). The 3-beta hydroxyl group of (XII) was then selectively oxidized to ketone (XIII) under Oppenauer conditions. Ketone (XIII) was converted to the primary amine (XV) via formation of the O-benzyl oxime (XIV), which was reduced by LiAlH4.

参考文献中间体

合成目标

【1】 Moriarty, R.M.; et al.; Synthesis of squalamine. A steroidal antibiotic from the shark. Tetrahedron Lett 1994, 35, 44, 8103.
【2】 Moriarty, R.M.; Guo, L.; Tuladhar, S.M. (Genaera Corp.); Chemical synthesis of squalamine. WO 9419366 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	53694	(3S,8S,9S,10R,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate	n/a	C₃₅H₆₂O₃Si	详情	详情
(IX)	53695	(3S,8S,9S,10R,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethyl-7-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate	n/a	C₃₅H₆₀O₄Si	详情	详情
(X)	53696	(3S,5R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate	n/a	C₃₅H₆₂O₄Si	详情	详情
(XI)	53697	(3S,5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate	n/a	C₃₅H₆₄O₄Si	详情	详情
(XII)	53698	(3S,5R,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol	n/a	C₃₃H₆₂O₃Si	详情	详情
(XIII)	53699	(5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one	n/a	C₃₃H₆₀O₃Si	详情	详情
(XIV)	53700	(5R,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one O-benzyloxime	n/a	C₄₀H₆₇NO₃Si	详情	详情
(XV)	53701	(3S,5R,7R,8R,9S,10S,13R,14S,17R)-3-amino-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol	n/a	C₃₃H₆₃NO₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Preparation of the key intermediate (XIII) starting from chenodeoxycholic acid (XLIV) was also reported. Diacetylation of (XLIV), followed by selective hydrolysis of diacetate (XLV), gave the C-3 alcohol (XLVI). This was oxidized to dienone (XLVII) following a previously reported procedure. Reduction of (XLVII) by lithium in liquid ammonia yielded the saturated ketone (XLVIII). Protection of the 7-hydroxyl group of (XLVIII) using methoxymethyl chloride, followed by ketalization of the 3-ketone, afforded (XLIX). Side-chain elongation in (XLIX) as in Scheme 20248401a produced (L), which was then deprotected giving (XIII).

参考文献中间体

合成目标

【1】 Moriarty, R.M.; Guo, L.; Tuladhar, S.M. (Genaera Corp.); Chemical synthesis of squalamine. WO 9419366 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IL)	53733		n/a	C₂₈H₄₆O₆	详情	详情
(VIII)	53699	(5S,7R,8R,9S,10S,13R,14S,17R)-17-((1R)-4-{[tert-butyl(dimethyl)silyl]oxy}-1,5-dimethylhexyl)-7-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one	n/a	C₃₃H₆₀O₃Si	详情	详情
(XLIV)	53728	(4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	n/a	C₂₄H₄₀O₄	详情	详情
(XLV)	53729	(4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-bis(acetyloxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	n/a	C₂₈H₄₄O₆	详情	详情
(XLVI)	53730	(4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-7-(acetyloxy)-3-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	n/a	C₂₆H₄₂O₅	详情	详情
(XLVII)	53731	(4R)-4-[(7R,8S,9S,10S,13R,14S,17R)-7-(acetyloxy)-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	n/a	C₂₆H₃₆O₅	详情	详情
(XLVIII)	53732	(4R)-4-[(5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	n/a	C₂₄H₃₈O₄	详情	详情
(L)	53734		n/a	C₃₁H₅₄O₅	详情	详情

Extended Information