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【结 构 式】 
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【分子编号】64640 【品名】(5R,7S)-5-[(benzyloxy)methyl]-7-[(2-{(2S)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-methoxypropyl}-1,3-dithian-2-yl)methyl]-2,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (2R,4S)-2,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2-{(2S)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-methoxypropyl}-1,3-dithian-2-yl)pentyl ether 【CA登记号】 |
【 分 子 式 】C37H68O6S2Si2 【 分 子 量 】729.24632 【元素组成】C 60.94% H 9.4% O 13.16% S 8.79% Si 7.7% |
合成路线1
该中间体在本合成路线中的序号：(LIII)Spiranic phenylsulfone intermediate (LXIII). The cyclization of the dithiane derivative (LIII) by means of HCL and Hg(ClO4)2/CaCO3 in acetonitrile/water gives a mixture of the desired spiroketal compound (LV) along with its isomer (LIV) that can be converted to (LV) by treatment with HClO4. The reaction of (LV) with Piv-Cl and TEA, followed by silylation with Tbdms-Cl and imidazole allows the selective silylation of the secondary OH group yielding (LVI). The cleavage of the Piv group of (LVI) by means of DIBAL in dichloromethane, followed by treatment with I2, PPh3 and imidazole in benzene affords the iodomethyl compound (LVII). The condensation of (LVII) with the dithiane intermediate (LII) by means of BuLi in THF/HMPA provides compound (LVIII), which is treated with Hg(ClO4)2 and CaCO3 and reduced with NaBH4 to cleave the dithiane auxiliary and yield alcohol (LIX). The protection of the OH group of (LIX) with Bom-Cl and DIEA affords compound (LX), which is reduced with DIBAL to cleave the cyclic ketal group and provide the primary alcohol (LXI). The reaction of (LXI) with I2, PPh3 and imidazole in benzene/acetonitrile gives the iodo derivative (LXII), which is finally treated with sodium phenylsulfinate in hot DMF to yield the desired spiranic phenylsulfone derivative (LXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (LII) | 64639 | (4S,5R)-2-(3,4-dimethylphenyl)-4-[(1S)-1-(1,3-dithian-2-yl)ethyl]-5-methyl-1,3-dioxane | C19H28O2S2 | 详情 | 详情 | |
| (LIII) | 64640 | (5R,7S)-5-[(benzyloxy)methyl]-7-[(2-{(2S)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-methoxypropyl}-1,3-dithian-2-yl)methyl]-2,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecane; benzyl (2R,4S)-2,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2-{(2S)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-methoxypropyl}-1,3-dithian-2-yl)pentyl ether | C37H68O6S2Si2 | 详情 | 详情 | |
| (LIV) | 64641 | (2R,4S,6R,8S,10S)-2-[(benzyloxy)methyl]-8-(hydroxymethyl)-10-methoxy-1,7-dioxaspiro[5.5]undecan-4-ol | C19H28O6 | 详情 | 详情 | |
| (LV) | 64642 | (2R,4S,6S,8S,10S)-2-[(benzyloxy)methyl]-8-(hydroxymethyl)-10-methoxy-1,7-dioxaspiro[5.5]undecan-4-ol | C19H28O6 | 详情 | 详情 | |
| (LVI) | 64643 | ((2S,4S,6S,8R,10S)-8-[(benzyloxy)methyl]-10-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)methyl pivalate | C30H50O7Si | 详情 | 详情 | |
| (LVII) | 64644 | benzyl [(2R,4S,6S,8S,10S)-4-{[tert-butyl(dimethyl)silyl]oxy}-8-(iodomethyl)-10-methoxy-1,7-dioxaspiro[5.5]undec-2-yl]methyl ether; {[(2R,4S,6S,8S,10S)-2-[(benzyloxy)methyl]-8-(iodomethyl)-10-methoxy-1,7-dioxaspiro[5.5]undec-4-yl]oxy}(tert-butyl)dimethylsilane | C25H41IO5Si | 详情 | 详情 | |
| (LVIII) | 64645 | benzyl {(2R,4S,6R,8S,10S)-4-{[tert-butyl(dimethyl)silyl]oxy}-8-[(2-{(1S)-1-[(4S,5R)-2-(3,4-dimethylphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl}-1,3-dithian-2-yl)methyl]-10-methoxy-1,7-dioxaspiro[5.5]undec-2-yl}methyl ether; ({(2R,4S,6R,8S,10S)-2-[(benzyloxy)methyl]-8-[(2-{(1S)-1-[(4S,5R)-2-(3,4-dimethylphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl}-1,3-dithian-2-yl)methyl]-10-methoxy-1,7-dioxaspiro[5.5]undec-4-yl}oxy)(tert-butyl)dimethylsilane | C44H68O7S2Si | 详情 | 详情 | |
| (LIX) | 64646 | (2R,3R)-1-((2R,4S,6R,8R,10S)-8-[(benzyloxy)methyl]-10-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-3-[(4S,5R)-2-(3,4-dimethylphenyl)-5-methyl-1,3-dioxan-4-yl]-2-butanol | C41H64O8Si | 详情 | 详情 | |
| (LX) | 64647 | ({(2R,4S,6R,8S,10S)-8-{(2R,3R)-2-[(benzyloxy)methoxy]-3-[(4S,5R)-2-(3,4-dimethylphenyl)-5-methyl-1,3-dioxan-4-yl]butyl}-2-[(benzyloxy)methyl]-10-methoxy-1,7-dioxaspiro[5.5]undec-4-yl}oxy)(tert-butyl)dimethylsilane; benzyl ((2R,4S,6R,8S,10S)-8-{(2R,3R)-2-[(benzyloxy)methoxy]-3-[(4S,5R)-2-(3,4-dimethylphenyl)-5-methyl-1,3-dioxan-4-yl]butyl}-4-{[tert-butyl(dimethyl)silyl]oxy}-10-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)methyl ether | C49H72O9Si | 详情 | 详情 | |
| (LXI) | 64648 | (2R,3S,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)-3-[(2,4-dimethoxybenzyl)oxy]-2,4-dimethyl-1-hexanol | C49H74O11Si | 详情 | 详情 | |
| (LXII) | 64649 | ({(2R,4S,6R,8S,10S)-8-{(2R,3S,4R,5S)-2-[(benzyloxy)methoxy]-4-[(2,4-dimethoxybenzyl)oxy]-6-iodo-3,5-dimethylhexyl}-2-[(benzyloxy)methyl]-10-methoxy-1,7-dioxaspiro[5.5]undec-4-yl}oxy)(tert-butyl)dimethylsilane; benzyl ((2R,4S,6R,8S,10S)-8-{(2R,3S,4R,5S)-2-[(benzyloxy)methoxy]-4-[(2,4-dimethoxybenzyl)oxy]-6-iodo-3,5-dimethylhexyl}-4-{[tert-butyl(dimethyl)silyl]oxy}-10-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)methyl ether | C49H73IO10Si | 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 |