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【结 构 式】 
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【分子编号】46095 【品名】(1S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-4-oxobutyl acetate 【CA登记号】 |
【 分 子 式 】C33H53BrO9 【 分 子 量 】673.68242 【元素组成】C 58.84% H 7.93% Br 11.86% O 21.37% |
合成路线1
该中间体在本合成路线中的序号：(XLI)The cyclization of (XXXVI) by means of Tes-H and Tms-OTf gives the tricyclic carbinol (XXXVII), which is oxidized with DMP and NaHCO3 to afford the carbaldehyde (XXXVIII). The condensation of carbaldehyde (XXXVIII) with the intermediate iodovinyl-tetrahydrofuran (XX) by means of CrCl2 (0.5% NiCl2) gives the unsaturated alcohol (XXXIX), which is oxidized with DMP and NaHCO3, yielding the corresponding ketone (XL). The hydrogenation of the double bond of (XL) with H2 over Pd/C in ethyl acetate affords the saturated ketone (XLI), which is treated with methylmagnesium bromide in THF to provide the tertiary alcohol (XLII). Finally, the acetoxy groups of (XLII) are hydrolyzed with K2CO3 in methanol to furnish an approximately 1:1 mixture of the trihydroxycompound (XLIII) and the target monoacetate, which are separated by chromatography.
| 【1】 Forsyth, G.J.; Gonzalez, I.C.; Total synthesis of tryrsiferyl 23-acetate, a specific inhibitor of protein phosphatase 2A and anti-leukemic inducer of apoptosis. J Am Chem Soc 2000, 122, 38, 9099. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XX) | 46075 | 1-[(2R,5R)-5-[(1S,2E)-1-(acetoxy)-3-iodo-2-propenyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C15H23IO5 | 详情 | 详情 | |
| (XXXVI) | 46089 | 1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-3-[(2S,3R,6R)-3-hydroxy-6-(hydroxymethyl)-2-methyltetrahydro-2H-pyran-2-yl]-1-propanone | C18H31BrO5 | 详情 | 详情 | |
| (XXXVII) | 46091 | [(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]methanol | C18H31BrO4 | 详情 | 详情 | |
| (XXXVIII) | 46092 | (2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-carbaldehyde | C18H29BrO4 | 详情 | 详情 | |
| (XXXIX) | 46093 | 1-[(2R,5R)-5-[(1S,2E,4R)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-(acetoxy)-4-hydroxy-2-butenyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C33H53BrO9 | 详情 | 详情 | |
| (XL) | 46094 | (1S,2E)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-4-oxo-2-butenyl acetate | C33H51BrO9 | 详情 | 详情 | |
| (XLI) | 46095 | (1S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-4-oxobutyl acetate | C33H53BrO9 | 详情 | 详情 | |
| (XLII) | 46096 | 1-[(2R,5R)-5-[(1S,4S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-(acetoxy)-4-hydroxypentyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C34H57BrO9 | 详情 | 详情 | |
| (XLIII) | 46097 | (1S,4S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-(1-hydroxy-1-methylethyl)-2-methyltetrahydro-2-furanyl]-1,4-pentanediol | C30H53BrO7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XLI)The cyclization of (XXXVI) by means of Tes-H and Tms-OTf gives the tricyclic carbinol (XXXVII), which is oxidized with DMP and NaHCO3 to afford the carbaldehyde (XXXVIII). The condensation of carbaldehyde (XXXVIII) with the intermediate iodovinyl-tetrahydrofuran (XX) by means of CrCl2 (0.5% NiCl2) gives the unsaturated alcohol (XXXIX), which is oxidized with DMP and NaHCO3, yielding the corresponding ketone (XL). The hydrogenation of the double bond of (XL) with H2 over Pd/C in ethyl acetate affords the saturated ketone (XLI), which is treated with methylmagnesium bromide in THF to provide the tertiary alcohol (XLII). Finally, the acetoxy groups of (XLII) are hydrolyzed with K2CO3 in methanol to furnish the target trihydroxycompound.
| 【1】 Forsyth, G.J.; Gonzalez, I.C.; Total synthesis of tryrsiferyl 23-acetate, a specific inhibitor of protein phosphatase 2A and anti-leukemic inducer of apoptosis. J Am Chem Soc 2000, 122, 38, 9099. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XX) | 46075 | 1-[(2R,5R)-5-[(1S,2E)-1-(acetoxy)-3-iodo-2-propenyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C15H23IO5 | 详情 | 详情 | |
| (XXXVI) | 46089 | 1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-3-[(2S,3R,6R)-3-hydroxy-6-(hydroxymethyl)-2-methyltetrahydro-2H-pyran-2-yl]-1-propanone | C18H31BrO5 | 详情 | 详情 | |
| (XXXVII) | 46091 | [(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]methanol | C18H31BrO4 | 详情 | 详情 | |
| (XXXVIII) | 46092 | (2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-carbaldehyde | C18H29BrO4 | 详情 | 详情 | |
| (XXXIX) | 46093 | 1-[(2R,5R)-5-[(1S,2E,4R)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-(acetoxy)-4-hydroxy-2-butenyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C33H53BrO9 | 详情 | 详情 | |
| (XL) | 46094 | (1S,2E)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-4-oxo-2-butenyl acetate | C33H51BrO9 | 详情 | 详情 | |
| (XLI) | 46095 | (1S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-4-oxobutyl acetate | C33H53BrO9 | 详情 | 详情 | |
| (XLII) | 46096 | 1-[(2R,5R)-5-[(1S,4S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-(acetoxy)-4-hydroxypentyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C34H57BrO9 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XLI)The cyclization of (XXXVI) by means of Tes-H and Tms-OTf gives the tricyclic carbinol (XXXVII), which is oxidized with DMP and NaHCO3 to afford the carbaldehyde (XXXVIII). The condensation of carbaldehyde (XXXVIII) with the intermediate iodovinyl-tetrahydrofuran (XX) by means of CrCl2 (0.5% NiCl2) gives the unsaturated alcohol (XXXIX), which is oxidized with DMP and NaHCO3, yielding the corresponding ketone (XL). The hydrogenation of the double bond of (XL) with H2 over Pd/C in ethyl acetate affords the saturated ketone (XLI), which is treated with methylmagnesium bromide in THF to provide the tertiary alcohol (XLII). The acetoxy groups of (XLII) are hydrolyzed with K2CO3 in methanol to furnish the trihydroxycompound (XLIII), which is finally regioselectively monoacetylated with Ac2O an pyridine to give the target monoacetate.
| 【1】 Forsyth, G.J.; Gonzalez, I.C.; Total synthesis of tryrsiferyl 23-acetate, a specific inhibitor of protein phosphatase 2A and anti-leukemic inducer of apoptosis. J Am Chem Soc 2000, 122, 38, 9099. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XX) | 46075 | 1-[(2R,5R)-5-[(1S,2E)-1-(acetoxy)-3-iodo-2-propenyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C15H23IO5 | 详情 | 详情 | |
| (XXXVI) | 46089 | 1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-3-[(2S,3R,6R)-3-hydroxy-6-(hydroxymethyl)-2-methyltetrahydro-2H-pyran-2-yl]-1-propanone | C18H31BrO5 | 详情 | 详情 | |
| (XXXVII) | 46091 | [(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]methanol | C18H31BrO4 | 详情 | 详情 | |
| (XXXVIII) | 46092 | (2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-carbaldehyde | C18H29BrO4 | 详情 | 详情 | |
| (XXXIX) | 46093 | 1-[(2R,5R)-5-[(1S,2E,4R)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-(acetoxy)-4-hydroxy-2-butenyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C33H53BrO9 | 详情 | 详情 | |
| (XL) | 46094 | (1S,2E)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-4-oxo-2-butenyl acetate | C33H51BrO9 | 详情 | 详情 | |
| (XLI) | 46095 | (1S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-4-oxobutyl acetate | C33H53BrO9 | 详情 | 详情 | |
| (XLII) | 46096 | 1-[(2R,5R)-5-[(1S,4S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-(acetoxy)-4-hydroxypentyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C34H57BrO9 | 详情 | 详情 | |
| (XLIII) | 46097 | (1S,4S)-4-[(2R,4aR,6R,8aS)-6-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-8a-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-[(2R,5R)-5-(1-hydroxy-1-methylethyl)-2-methyltetrahydro-2-furanyl]-1,4-pentanediol | C30H53BrO7 | 详情 | 详情 |