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【结 构 式】 
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【分子编号】62166 【品名】(4aR,6S,8aR)-6-methoxy-2-(4-methoxyphenyl)-6-methyltetrahydropyrano[3,2-d][1,3]dioxin-8(4H)-one 【CA登记号】 |
【 分 子 式 】C16H20O6 【 分 子 量 】308.3312 【元素组成】C 62.33% H 6.54% O 31.13% |
合成路线1
该中间体在本合成路线中的序号：(XXX)2-Deoxy-D-glucose (XXII) is protected as the cyclic acetal (XXIV) employing p methoxybenzaldehyde dimethyl acetal (XXIII) in the presence of TsOH. Subsequent oxidation of the anomeric hydroxyl group of (XXIV) with Br2 leads to lactone (XXV). After protection of the remaining 3-hydroxyl group of (XXV) as the silyl ether (XXVI), olefination with the Tebbe reagent provides the exocyclic vinyl ether (XXVII). Treatment of (XXVII) with PPTS and MeOH affords a separable mixture of epimeric methylketals (XXVIII). Desilylation of the desired isomer yields alcohol (XXIX), which is then oxidized to ketone (XXX) employing the Dess-Martin periodinane reagent.
| 【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 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXII) | 62159 | (4R,5S,6R)-6-(hydroxymethyl)tetrahydro-2H-pyran-2,4,5-triol | C6H12O5 | 详情 | 详情 | |
| (XXIII) | 26485 | 1-(dimethoxymethyl)-4-methoxybenzene | 2186-92-7 | C10H14O3 | 详情 | 详情 |
| (XXIV) | 62160 | (4aR,8R,8aS)-2-(4-methoxyphenyl)hexahydropyrano[3,2-d][1,3]dioxine-6,8-diol | C14H18O6 | 详情 | 详情 | |
| (XXV) | 62161 | (4aR,8R,8aS)-8-hydroxy-2-(4-methoxyphenyl)tetrahydropyrano[3,2-d][1,3]dioxin-6(4H)-one | C14H16O6 | 详情 | 详情 | |
| (XXVI) | 62162 | (4aR,8R,8aR)-8-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-methoxyphenyl)tetrahydropyrano[3,2-d][1,3]dioxin-6(4H)-one | C20H30O6Si | 详情 | 详情 | |
| (XXVII) | 62163 | {[(4aR,8R,8aR)-2-(4-methoxyphenyl)-6-methylenehexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy}(tert-butyl)dimethylsilane; 4-((4aR,8R,8aR)-8-{[tert-butyl(dimethyl)silyl]oxy}-6-methylenehexahydropyrano[3,2-d][1,3]dioxin-2-yl)phenyl methyl ether | C21H32O5Si | 详情 | 详情 | |
| (XXVIII) | 62164 | 4-((4aR,8R,8aR)-8-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methylhexahydropyrano[3,2-d][1,3]dioxin-2-yl)phenyl methyl ether; {[(4aR,8R,8aR)-6-methoxy-2-(4-methoxyphenyl)-6-methylhexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy}(tert-butyl)dimethylsilane | C22H36O6Si | 详情 | 详情 | |
| (XXIX) | 62165 | (4aR,6S,8R,8aS)-6-methoxy-2-(4-methoxyphenyl)-6-methylhexahydropyrano[3,2-d][1,3]dioxin-8-ol | C16H22O6 | 详情 | 详情 | |
| (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 |
合成路线2
该中间体在本合成路线中的序号：(XXX)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.
| 【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 | CAS号 | 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 |