(1R,3S,5S,6R,9R,10R,11R,13R,14S,15R,17S,18S,19R,25R,27S,29S,31S,33S,36S,37S,38R,41S,43S,49S)-3,37-bis(acetyloxy)-17,27-bis{[tert-butyl(dimethyl)silyl]oxy}-11-((4S,5E)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-methylene-5,7-octadienyl)-10-hydroxy-15,31-dimethoxy-18,36,38,43,49-pentamethyl-39-methylene-7,35-dioxo-14,43-bis[(triethylsilyl)oxy]-8,12,45,46,47,48-hexaoxaheptacyclo[39.3.1.1~1,5~.1~9,13~.1~15,19~.1~25,29~.1~29,33~] -Drug Synthesis Database

【结构式】

【分子编号】64660

【品名】(1R,3S,5S,6R,9R,10R,11R,13R,14S,15R,17S,18S,19R,25R,27S,29S,31S,33S,36S,37S,38R,41S,43S,49S)-3,37-bis(acetyloxy)-17,27-bis{[tert-butyl(dimethyl)silyl]oxy}-11-((4S,5E)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-methylene-5,7-octadienyl)-10-hydroxy-15,31-dimethoxy-18,36,38,43,49-pentamethyl-39-methylene-7,35-dioxo-14,43-bis[(triethylsilyl)oxy]-8,12,45,46,47,48-hexaoxaheptacyclo[39.3.1.1~1,5~.1~9,13~.1~15,19~.1~25,29~.1~29,33~]

【CA登记号】

【分子式】C₉₆H₁₇₀O₂₂Si₅

【分子量】1816.8201

【元素组成】C 63.47% H 9.43% O 19.37% Si 7.73%

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：(LXXIII)

The cleavage of the Bom and benzyl protecting groups of (LXIX) by means of 1-methyl-1,4-cyclohexadiene and Pd(OH)2/C in ethanol, followed by oxidation with DMP gives the ketonic carbaldehyde compound (LXX) (4), which is condensed with the advanced intermediate phosphonium salt (XLI) by means of NaHMDS in toluene to yield the adduct (LXXI). The selective deprotection of the Tms silyl ester groups of (LXXI) with KF in methanol affords the dihydroxyacid (LXXII), which is submitted to macrolactonization by means of 2,4,6-trichlorobenzoyl chloride, DIEA and DMAP in toluene to provide the macrolactone (LXXIII). The fully desilylation of (LXXIII) by means of HF in acetonitrile/water gives rise to a 1:3 mixture of spongistatin 2 and its epimer (LXXIV) with the unnatural configuration being predominant. Perchloric acid mediated epimerization of (LXXIV) in the presence of calcium perchlorate leads to a 3.9-2.3:1 mixture (with the natural configuration being predominant), along with some degradation products (2).

参考文献中间体

合成目标

【2】 Smith, A.B. III; Lin, Q.; Doughty, V.A.; Zhuang, L.; McBriar, M.D.; Kerns, J.K.; Brook, C.S.; Murase, N.; Nakayama, K.; The spongistatins: Architecturally complex natural products - Part two: Synthesis of the C(29-51) subunit, fragment assembly, and final elaboration to (+)-spongistatin 2. Angew Chem. Int Ed 2001, 40, 1, 196.
【1】 Smith, A.B.; et al.; The spongistatins: Architecturally complex natural products - Part one: A formal synthesis of (+)-spongistatin 1 by construction of an advanced ABCD fragment. Angew Chem. Int Ed 2001, 40, 1, 191.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XLI)	64629	[4-((2R,3S,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-{(S)-{(2R,3S,4R,5R,6R)-6-((4S,5E)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-methylene-5,7-octadienyl)-3-methyl-4,5-bis[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}[(triethylsilyl)oxy]methyl}-6-methoxy-3-methyltetrahydro-2H-pyran-2-yl)butyl](triphenyl)phosphonium iodide	C₆₉H₁₁₈IO₈PSi₅	详情	详情
(LXIX)	64656	triisopropylsilyl 2-{(2S,4S,6R,8S,10S)-10-(acetyloxy)-2-{2-[(1R,2S,3R,4R)-2-(acetyloxy)-4-[(benzyloxy)methoxy]-5-((2S,4S,8R,10S)-8-[(benzyloxy)methyl]-10-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-1,3-dimethylpentyl]-2-propenyl}-4-methyl-4-[(triethylsilyl)oxy]-1-oxaspiro[5.5]undec-8-yl}acetate	C₇₄H₁₂₄O₁₅Si₃	详情	详情
(LXX)	64657	triisopropylsilyl 2-{(2S,4S,6R,8S,10S)-10-(acetyloxy)-2-{2-[(1R,2S,3S)-2-(acetyloxy)-5-((2S,4S,6R,8R,10S)-10-{[tert-butyl(dimethyl)silyl]oxy}-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-1,3-dimethyl-4-oxopentyl]-2-propenyl}-4-methyl-4-[(triethylsilyl)oxy]-1-oxaspiro[5.5]undec-8-yl}acetate	C₅₉H₁₀₆O₁₄Si₃	详情	详情
(LXXI)	64658		C₁₁₀H₂₀₈O₂₁Si₈	详情	详情
(LXXII)	64659		C₉₅H₁₇₂O₂₁Si₅	详情	详情
(LXXIII)	64660	(1R,3S,5S,6R,9R,10R,11R,13R,14S,15R,17S,18S,19R,25R,27S,29S,31S,33S,36S,37S,38R,41S,43S,49S)-3,37-bis(acetyloxy)-17,27-bis{[tert-butyl(dimethyl)silyl]oxy}-11-((4S,5E)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-methylene-5,7-octadienyl)-10-hydroxy-15,31-dimethoxy-18,36,38,43,49-pentamethyl-39-methylene-7,35-dioxo-14,43-bis[(triethylsilyl)oxy]-8,12,45,46,47,48-hexaoxaheptacyclo[39.3.1.1~1,5~.1~9,13~.1~15,19~.1~25,29~.1~29,33~]	C₉₆H₁₇₀O₂₂Si₅	详情	详情
(LXXIV)	64661	(1R,3S,5S,6R,9R,10R,11R,13R,14S,15R,17S,18R,19R,25R,27S,29S,31S,33S,36S,37S,38R,41S,43S,49S)-3,37-bis(acetyloxy)-10,14,17,27,43-pentahydroxy-11-[(4S,5E)-4-hydroxy-2-methylene-5,7-octadienyl]-15,31-dimethoxy-18,36,38,43,49-pentamethyl-39-methylene-7,35-dioxo-8,12,45,46,47,48-hexaoxaheptacyclo[39.3.1.1~1,5~.1~9,13~.1~15,19~.1~25,29~.1~29,33~]	C₆₆H₁₀₀O₂₂	详情	详情

Extended Information