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

【结构式】

【分子编号】53815

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

【CA登记号】n/a

【分子式】C₂₇H₄₆O₃

【分子量】418.66044

【元素组成】C 77.46% H 11.07% O 11.46%

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：(CXXXIX)

Steroid (CV) was treated with the fungal species Diplodia gossipina to yield the 7-hydroxylated compound (CXXXII) as a fermentation metabolite. Reduction of enone (CXXXII) by lithium in liquid ammonia afforded the saturated ketone (CXXXIII), which was subsequently protected as the ethylene ketal (CXXXIV) by treatment with ethylene glycol and chlorotrimethylsilane. Selective oxidation of the C-22 alcohol group of (CXXXIV) with NaOCl in the presence of TEMPO provided aldehyde (CXXXV). Wadsworth-Emmons condensation of (CXXXV) with phosphonate (CXV) gave enone (CXXXVI). Stereoselective reduction of (CXXXVI) to the 24-(S)-alcohol (CXXXVII) was achieved by treatment with borane-tetrahydrofuran complex in the presence of the chiral catalyst (R)-MeCBS. After catalytic hydrogenation of the double bond of (CXXXVII), the resultant ketal (CXXXVIII) was hydrolyzed to ketone (CXXXIX) under acidic conditions. Sulfation of (CXXXIX) by means of sulfur trioxide-pyridine furnished the key precursor (CXXI), which was then reductively aminated as in the precedent Scheme

参考文献中间体

合成目标

【1】 Kinney, W.A.; et al.; A short formal synthesis of squalamine from a microbial metabolite. Org Lett 2000, 2, 19, 2921.
【2】 Kinney, W.A.; Zhang, X.; Michalak, R. (Genaera Corp.); A process for the preparation of 7alpha-hydroxy 3-aminosubstd. sterols using intermediates with an unprotected 7alpha-hydroxy group. WO 0179255 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(CV)	53783	(8S,9S,10R,13S,14S,17R)-17-[(1S)-2-hydroxy-1-methylethyl]-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one	n/a	C₂₂H₃₄O₂	详情	详情
(CXV)	53793	diethyl 3-methyl-2-oxobutylphosphonate	n/a	C₉H₁₉O₄P	详情	详情
(CXXI)	53799	(1R,4R)-4-[(5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-isopropylpentyl hydrogen sulfate	n/a	C₂₇H₄₆O₆S	详情	详情
(CXXXII)	53808	(7R,8S,9S,10R,13R,14S,17R)-7-hydroxy-17-[(1S)-2-hydroxy-1-methylethyl]-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one	n/a	C₂₂H₃₄O₃	详情	详情
(CXXXIII)	53809	(5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-17-[(1S)-2-hydroxy-1-methylethyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one	n/a	C₂₂H₃₆O₃	详情	详情
(CXXXIV)	53810		n/a	C₂₄H₄₀O₄	详情	详情
(CXXXV)	53811		n/a	C₂₄H₃₈O₄	详情	详情
(CXXXVI)	53812		n/a	C₂₉H₄₆O₄	详情	详情
(CXXXVII)	53813		n/a	C₂₉H₄₈O₄	详情	详情
(CXXXVIII)	53814		n/a	C₂₉H₅₀O₄	详情	详情
(CXXXIX)	53815	(5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one	n/a	C₂₇H₄₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(CXXXIX)

The tertiary alcohol group of (CXLVII) was dehydrated to (CXLVIII) upon treatment with methanesulfonyl chloride and triethylamine. Diimide reduction of the olefin double bond of (CXLVIII) produced (CXLIX). The acetate ester of (CXLIX) was further hydrolyzed to alcohol (CL) by methanolic KOH. Then, acidic hydrolysis of the ketal protecting groups of (CL) furnished the key precursor (CXXXIX).

参考文献中间体

合成目标

【1】 Zhou, X.D.; et al.; A new highly stereoselective construction of the sidechain of squalamine through improved Sharpless catalytic asymmetric dihydroxylation. Tetrahedron Lett 2001, 42, 13, 2537.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(CXXXIX)	53815	(5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one	n/a	C₂₇H₄₆O₃	详情	详情
(CXLVII)	53823		n/a	C₃₃H₅₆O₇	详情	详情
(CXLVIII)	53824		n/a	C₃₃H₅₄O₆	详情	详情
(CXLIX)	53825		n/a	C₃₃H₅₆O₆	详情	详情
(CL)	53826		n/a	C₃₁H₅₄O₅	详情	详情

Extended Information