(2S,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-carbaldehyde -Drug Synthesis Database

【结构式】

【分子编号】62173

【品名】(2S,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-carbaldehyde

【CA登记号】

【分子式】C₁₅H₂₈O₄Si

【分子量】300.47042

【元素组成】C 59.96% H 9.39% O 21.3% Si 9.35%

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：(XXXVII)

Tebbe methylenation of ketone (XXX) gives the exo-olefin (XXXI). The p methoxybenzylidene acetal moiety of (XXXI) is then reduced with DIBAL to generate the p-methoxybenzyl ether (XXXII). The free hydroxyl group of (XXXII) is then acylated with pivaloyl chloride, providing pivalate ester (XXXIII). Removal of the p-methoxybenzyl group of (XXXIII) by treatment with DDQ, followed by reprotection of the resultant alcohol (XXXIV) with t-butyldimethylsilyl triflate leads to silyl ether (XXXV). The pivalate ester group of (XXXV) is then cleaved by treatment with DIBAL to afford alcohol (XXXVI), which is oxidized to aldehyde (XXXVII) by using the Dess-Martin periodinane.

参考文献中间体

合成目标

【1】 Horigome, M.; Motoyoshi, H.; Watanabe, H.; Kitahara, T.; A synthesis of FR901464. Tetrahedron Lett 2001, 42, 46, 8207.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXX)	62166	(4aR,6S,8aR)-6-methoxy-2-(4-methoxyphenyl)-6-methyltetrahydropyrano[3,2-d][1,3]dioxin-8(4H)-one	C₁₆H₂₀O₆	详情	详情
(XXXI)	62167	(4aR,6S,8aS)-6-methoxy-2-(4-methoxyphenyl)-6-methyl-8-methylenehexahydropyrano[3,2-d][1,3]dioxine; 4-[(4aR,6S,8aS)-6-methoxy-6-methyl-8-methylenehexahydropyrano[3,2-d][1,3]dioxin-2-yl]phenyl methyl ether	C₁₇H₂₂O₅	详情	详情
(XXXII)	62168	{(2R,3S,6S)-6-methoxy-3-[(4-methoxybenzyl)oxy]-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl}methanol	C₁₇H₂₄O₅	详情	详情
(XXXIII)	62169	{(2R,3S,6S)-6-methoxy-3-[(4-methoxybenzyl)oxy]-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl}methyl pivalate	C₂₂H₃₂O₆	详情	详情
(XXXIV)	62170	[(2R,3S,6S)-3-hydroxy-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]methyl pivalate	C₁₄H₂₄O₅	详情	详情
(XXXV)	62171	((2R,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl)methyl pivalate	C₂₀H₃₈O₅Si	详情	详情
(XXXVI)	62172	((2R,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl)methanol	C₁₅H₃₀O₄Si	详情	详情
(XXXVII)	62173	(2S,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-carbaldehyde	C₁₅H₂₈O₄Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVII)

Condensation of sulfone (XXI) with aldehyde (XXXVII), followed by treatment with benzoyl chloride affords adduct (XXXVIII). Reductive elimination of sulfone (XXXVIIII) with sodium amalgam leads to the conjugated diene (XXXIX). Both O-silyl groups of (XXXIX) are removed by treatment with tetrabutylammonium fluoride, providing diol (XL). Then, esterification of (XL) with acetic anhydride and DMAP furnishes diacetate (XLI).

参考文献中间体

合成目标

【1】 Horigome, M.; Motoyoshi, H.; Watanabe, H.; Kitahara, T.; A synthesis of FR901464. Tetrahedron Lett 2001, 42, 46, 8207.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXI)	62158	(Z,4S)-4-{[tert-butyl(diphenyl)silyl]oxy}-N-((2R,3R,5S,6S)-2,5-dimethyl-6-{(E)-3-methyl-4-[(4-methylphenyl)sulfonyl]-2-butenyl}tetrahydro-2H-pyran-3-yl)-2-pentenamide	C₄₀H₅₃NO₅SSi	详情	详情
(XXVII)	62173	(2S,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-carbaldehyde	C₁₅H₂₈O₄Si	详情	详情
(XXXVIII)	62174	(1S,3E)-1-((2R,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl)-5-{(2S,3S,5R,6R)-5-[((Z,4S)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-pentenoyl)amino]-3,6-dimethyltetrahydro-2H-pyran-2-yl}-3-methyl-2-[(4-methylphenyl)sulfonyl]-3-pentenyl benzoate	C₆₂H₈₅NO₁₀SSi₂	详情	详情
(XXXIX)	62175	(Z,4S)-N-{(2R,3R,5S,6S)-6-[(2E,4E)-5-((2R,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl)-3-methyl-2,4-pentadienyl]-2,5-dimethyltetrahydro-2H-pyran-3-yl}-4-{[tert-butyl(diphenyl)silyl]oxy}-2-pentenam	C₄₈H₇₃NO₆Si₂	详情	详情
(XL)	62176	(Z,4S)-4-hydroxy-N-((2R,3R,5S,6S)-6-{(2E,4E)-5-[(2R,3S,6S)-3-hydroxy-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)-2-pentenamide	C₂₆H₄₁NO₆	详情	详情
(XLI)	62177	(1S,2Z)-4-[((2R,3R,5S,6S)-6-{(2E,4E)-5-[(2R,3S,6S)-3-(acetyloxy)-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)amino]-1-methyl-4-oxo-2-butenyl acetate	C₃₀H₄₅NO₈	详情	详情

Extended Information