tert-butyl(dimethyl)silyl (2R,4S,6R)-2-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-4-yl ether; tert-butyl[2-((4S,6S)-6-{[(2R,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-2-yl]methyl}-2,2-dimethyl-1,3-dioxan-4-yl)ethoxy]diphenylsilane -Drug Synthesis Database

【结构式】

【分子编号】64635

【品名】tert-butyl(dimethyl)silyl (2R,4S,6R)-2-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-4-yl ether; tert-butyl[2-((4S,6S)-6-{[(2R,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-2-yl]methyl}-2,2-dimethyl-1,3-dioxan-4-yl)ethoxy]diphenylsilane

【CA登记号】

【分子式】C₃₉H₆₃IO₆Si₂

【分子量】811.00109

【元素组成】C 57.76% H 7.83% I 15.65% O 11.84% Si 6.93%

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：(XLVII)

Iodomethyl tetrahydropyran intermediate (XLVII): The condensation between epoxides (XLII), (XLIV) and silylated 1,3-dithiane (XLIII) gives the dihydroxy compound (XLV), which is treated first with 2,2-dimethoxypropane (XVIII) to create an acetonide group, and then with Hg(ClO4)2 to promote cyclization to yield the tetrahydropyran derivative (XLVI). Finally, the TsO group of (XLVI) is treated with lithium iodide in methanol to afford the desired iodomethyl tetrahydropyran intermediate (XLVII)

参考文献中间体

合成目标

【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	CAS号	分子式	供应商	用于合成
(XVIII)	10722	1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane	77-76-9	C₅H₁₂O₂	详情	详情
(XLII)	64630	tert-butyl(diphenyl)silyl (3S)-4-[(2S)oxiranyl]-3-[(triethylsilyl)oxy]butyl ether; (7S)-9,9-diethyl-2,2-dimethyl-7-[(2S)oxiranylmethyl]-3,3-diphenyl-4,8-dioxa-3,9-disilaundecane		C₂₈H₄₄O₃Si₂	详情	详情
(XLIII)	64631	tert-butyl(1,3-dithian-2-yl)dimethylsilane		C₁₀H₂₂S₂Si	详情	详情
(XLIV)	64632	(4R)-2,2-dimethyl-4-{[(2S)-2-methyloxiranyl]methyl}-1,3-dioxolane		C₉H₁₆O₃	详情	详情
(XLV)	64633	(2R,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[2-((2S,4S)-6-{[tert-butyl(diphenyl)silyl]oxy}-2,4-dihydroxyhexyl)-1,3-dithian-2-yl]-2,4-dimethylpentyl 4-methylbenzenesulfonate		C₄₆H₇₂O₇S₃Si₂	详情	详情
(XLVI)	64634	((2R,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-methoxy-4-methyltetrahydro-2H-pyran-2-yl)methyl 4-methylbenzenesulfonate		C₄₆H₇₀O₉SSi₂	详情	详情
(XLVII)	64635	tert-butyl(dimethyl)silyl (2R,4S,6R)-2-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-4-yl ether; tert-butyl[2-((4S,6S)-6-{[(2R,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-2-yl]methyl}-2,2-dimethyl-1,3-dioxan-4-yl)ethoxy]diphenylsilane		C₃₉H₆₃IO₆Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XLVII)

Assembly of the target compound. The condensation of the iodomethyl tetrahydropyran intermediate (XLVII) with the spiranic phenylsulfone derivative (LXIII) by means of BuLi in toluene gives the adduct (LXIV), which is desulfurized by methylenation with CH2I2 and i-PrMgCl in THF/HMPA to yield (LXV). The reaction of (LXV) with TBAF, followed by selective resilylation with Tbdms-Cl and imidazole and cleavage of the acetonide group with concomitant spiroketalization by means of HClO4 affords the bis spiroketal compound (LXVI). The cleavage of the benzyl ether group of (LXVI) by means of DDQ, followed by selective acetylation of the secondary OH group provides acetate (LXVII), which is silylated with Tes-OTf and lutidine, and selectively deprotected by means of HF and pyridine to give the primary alcohol (LXVIII). The oxidation of (LXVIII) with DMP and NaClO2, followed by silylation with Tips-Cl and TEA yields the silyl ester (LXIX).

参考文献中间体

合成目标

【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
(XLVII)	64635	tert-butyl(dimethyl)silyl (2R,4S,6R)-2-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-4-yl ether; tert-butyl[2-((4S,6S)-6-{[(2R,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(iodomethyl)-2-methoxy-4-methyltetrahydro-2H-pyran-2-yl]methyl}-2,2-dimethyl-1,3-dioxan-4-yl)ethoxy]diphenylsilane	C₃₉H₆₃IO₆Si₂	详情	详情
(LXIII)	64650	(2S,3R,4S,5R)-5-[(benzyloxy)methoxy]-6-((2S,4S,8R,10S)-8-[(benzyloxy)methyl]-10-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-3-[(2,4-dimethoxybenzyl)oxy]-2,4-dimethylhexyl phenyl sulfone; ({(2R,4S,8S,10S)-8-[(2R,3S,4R,5S)-2-[(benzyloxy)methoxy]-4-[(2,4-dimethoxybenzyl)oxy]-3,5-dimethyl-6-(phenylsulfonyl)hexyl]-2-[(benzyloxy)methyl]-10-methoxy-1,7-dioxaspiro[5.5]undec-4-yl}oxy)(tert-butyl)dimethylsilane	C₅₅H₇₈O₁₂SSi	详情	详情
(LXIV)	64651	(2S,3R,4S,5R)-5-[(benzyloxy)methoxy]-6-((2S,4S,6R,8R,10S)-8-[(benzyloxy)methyl]-10-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-1-[((2R,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-methoxy-4-methyltetrahydro-2H-pyran-2-yl)methyl]-3-[(2,4-dimethoxybenzyl)oxy]-2,4-dimethylhexyl phenyl sulfone; ({(2R,4S,6R,8S,10S)-8-[(2R,3S,4R,5S)-2-[(benzyloxy)methoxy]-7-((2R,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-methoxy-4-methyltetrahydro-2H-pyran-2-yl)-4-[(2,4-dimethoxybenzyl)oxy]-3,5-dimethyl-6-(phenylsulfonyl)heptyl]-2-[(benzyloxy)methyl]-10-methoxy-1,7-dioxaspiro[5.5]undec-4-yl}oxy)(tert-butyl)dimethylsilane	C₉₄H₁₄₀O₁₈SSi₃	详情	详情
(LXV)	64652	({(2R,4S,8S,10S)-8-{(2R,3S,4S,5R)-2-[(benzyloxy)methoxy]-6-[((2S,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-methoxy-4-methyltetrahydro-2H-pyran-2-yl)methyl]-4-[(2,4-dimethoxybenzyl)oxy]-3,5-dimethyl-6-heptenyl}-2-[(benzyloxy)methyl]-10-methoxy-1,7-dioxaspiro[5.5]undec-4-yl}oxy)(tert-butyl)dimethylsilane; benzyl ((2R,4S,8S,10S)-8-{(2R,3S,4S,5R)-2-[(benzyloxy)methoxy]-6-[((2S,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-{[(4S,6S)-6-(2-{[tert-butyl(diphenyl)silyl]oxy}ethyl)-2,2-dimethyl-1,3-dioxan-4-yl]methyl}-6-methoxy-4-methyltetrahydro-2H-pyran-2-yl)methyl]-4-[(2,4-dimethoxybenzyl)oxy]-3,5-dimethyl-6-heptenyl}-4-{[tert-butyl(dimethyl)silyl]oxy}-10-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)methyl ether	C₈₉H₁₃₆O₁₆Si₃	详情	详情
(LXVI)	64653	(2S,4S,6R,8S,10S)-2-(2-{(1R,2S,3S,4R)-4-[(benzyloxy)methoxy]-5-((2S,4S,6S,8R,10S)-8-[(benzyloxy)methyl]-10-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-2-[(2,4-dimethoxybenzyl)oxy]-1,3-dimethylpentyl}-2-propenyl)-10-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-methyl-1-oxaspiro[5.5]undecane-4,8-diol	C₇₀H₁₁₂O₁₄Si₂	详情	详情
(LXVII)	64654	(2S,4S,6R,8S,10S)-2-{2-[(1R,2S,3R,4R)-2-(acetyloxy)-4-[(benzyloxy)methoxy]-5-((2S,4S,6S,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}-10-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-hydroxy-4-methyl-1-oxaspiro[5.5]undec-8-yl acetate	C₆₅H₁₀₆O₁₄Si₂	详情	详情
(LXVIII)	64655	(2S,4S,6R,8S,10S)-2-{2-[(1R,2S,3R,4R)-2-(acetyloxy)-4-[(benzyloxy)methoxy]-5-((2S,4S,6S,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}-10-(2-hydroxyethyl)-4-methyl-4-[(triethylsilyl)oxy]-1-oxaspiro[5.5]undec-8-yl acetate	C₆₅H₁₀₆O₁₄Si₂	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

Extended Information