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【结 构 式】 
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【分子编号】46061 【品名】[(2R,3R)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol 【CA登记号】 |
【 分 子 式 】C10H18O2 【 分 子 量 】170.25172 【元素组成】C 70.55% H 10.66% O 18.79% |
合成路线1
该中间体在本合成路线中的序号：(V)The regio- and stereoselective hydrolysis of (2R,3R)-epoxygeraniol (V) with HClO4 in THF/water gives the trihydroxy compound (VI), which is selectively benzoylated with benzoyl chloride, TEA and DMAP to yield the dibenzoate (VII). The reaction of (VII) with TBCO in nitromethane affords a mixture of tetrahydrofuran (VIII) and tetrahydropyran (IX), which are separated by chromatography. The desired isomer (X) is hydrolyzed with K2CO3 in methanol to provide the alpha-diol (XI), which is finally oxidized with NaIO4 in THF/water to furnish the target aldehydic intermediate (IV).
| 【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 |
|---|---|---|---|---|---|---|
| (IV) | 46060 | (2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-carbaldehyde | C9H15BrO2 | 详情 | 详情 | |
| (V) | 46061 | [(2R,3R)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol | C10H18O2 | 详情 | 详情 | |
| (VI) | 46062 | (2R,3S)-3,7-dimethyl-6-octene-1,2,3-triol | C10H20O3 | 详情 | 详情 | |
| (VII) | 46063 | (2R,3S)-2,3-bis(benzoyloxy)-3,7-dimethyl-6-octenyl benzoate | C31H32O6 | 详情 | 详情 | |
| (VIII) | 46064 | (2R)-2-(benzoyloxy)-2-[(2S)-5-(1-bromo-1-methylethyl)-2-methyltetrahydro-2-furanyl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (IX) | 46065 | (1R)-2-(benzoyloxy)-1-[(2S)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (X) | 46066 | (1R)-2-(benzoyloxy)-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (XI) | 46067 | (1R)-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-1,2-ethanediol | C10H19BrO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)The tetrahydrofuran intermediate (XX) has been obtained as follows: The reaction of (2S,3S)-epoxygeraniol (XII) with Bn-Br and NaH in THF gives the benzyl ether (XIII), which is treated with NaClO4 to yield the diol (XIV). The selective monoacetylation of (XI) with Ac2O and pyridine affords the monoacetate (XV), which is cyclized by means of (CF3CO2)ReO3 and TFAA to provide the tetrahydrofuran (XVI). The acetylation of the tertiary alcohol of (XVI) with Ac2O and Sc(OTf)3 gives the diacetate (XVII), which is debenzylated with H2 over Pd/C to yield the primary alcohol (XVIII). The oxidation of (XVIII) with DMP affords the carbaldehyde (XIX), which is finally condensed with iodoform and CrCl2 to furnish the target iodovinyl-tetrahydrofuran intermediate (XX).
| 【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 |
|---|---|---|---|---|---|---|
| (XII) | 46061 | [(2R,3R)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol | C10H18O2 | 详情 | 详情 | |
| (XIII) | 46068 | benzyl [(2S,3S)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methyl ether; (2S,3S)-3-[(benzyloxy)methyl]-2-methyl-2-(4-methyl-3-pentenyl)oxirane | C17H24O2 | 详情 | 详情 | |
| (XIV) | 46069 | (2S,3R)-1-(benzyloxy)-3,7-dimethyl-6-octene-2,3-diol | C17H26O3 | 详情 | 详情 | |
| (XV) | 46070 | (1S,2R)-1-[(benzyloxy)methyl]-2-hydroxy-2,6-dimethyl-5-heptenyl acetate | C19H28O4 | 详情 | 详情 | |
| (XVI) | 46071 | (1S)-2-(benzyloxy)-1-[(2R,5R)-5-(1-hydroxy-1-methylethyl)-2-methyltetrahydro-2-furanyl]ethyl acetate | C19H28O5 | 详情 | 详情 | |
| (XVII) | 46072 | 1-[(2R,5R)-5-[(1S)-1-(acetoxy)-2-(benzyloxy)ethyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C21H30O6 | 详情 | 详情 | |
| (XVIII) | 46073 | 1-[(2R,5R)-5-[(1S)-1-(acetoxy)-2-hydroxyethyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C14H24O6 | 详情 | 详情 | |
| (XIX) | 46074 | (1R)-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-2-oxoethyl acetate | C14H22O6 | 详情 | 详情 | |
| (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 |
合成路线3
该中间体在本合成路线中的序号：(V)The regio- and stereoselective hydrolysis of (2R,3R)-epoxygeraniol (V) with HClO4 in THF/water gives the trihydroxy compound (VI), which is selectively benzoylated with benzoyl chloride, TEA and DMAP to yield the dibenzoate (VII). The reaction of (VII) with TBCO in nitromethane affords a mixture of tetrahydrofuran (VIII) and tetrahydropyran (IX), which are separated by chromatography. The desired isomer (X) is hydrolyzed with K2CO3 in methanol to provide the alpha-diol (XI), which is finally oxidized with NaIO4 in THF/water to furnish the target aldehydic intermediate (IV).
| 【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 |
|---|---|---|---|---|---|---|
| (IV) | 46060 | (2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-carbaldehyde | C9H15BrO2 | 详情 | 详情 | |
| (V) | 46061 | [(2R,3R)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol | C10H18O2 | 详情 | 详情 | |
| (VI) | 46062 | (2R,3S)-3,7-dimethyl-6-octene-1,2,3-triol | C10H20O3 | 详情 | 详情 | |
| (VII) | 46063 | (2R,3S)-2,3-bis(benzoyloxy)-3,7-dimethyl-6-octenyl benzoate | C31H32O6 | 详情 | 详情 | |
| (VIII) | 46064 | (2R)-2-(benzoyloxy)-2-[(2S)-5-(1-bromo-1-methylethyl)-2-methyltetrahydro-2-furanyl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (IX) | 46065 | (1R)-2-(benzoyloxy)-1-[(2S)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (X) | 46066 | (1R)-2-(benzoyloxy)-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (XI) | 46067 | (1R)-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-1,2-ethanediol | C10H19BrO3 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XII)The tetrahydrofuran intermediate (XX) has been obtained as follows: The reaction of (2S,3S)-epoxygeraniol (XII) with Bn-Br and NaH in THF gives the benzyl ether (XIII), which is treated with NaClO4 to yield the diol (XIV). The selective monoacetylation of (XI) with Ac2O and pyridine affords the monoacetate (XV), which is cyclized by means of (CF3CO2)ReO3 and TFAA to provide the tetrahydrofuran (XVI). The acetylation of the tertiary alcohol of (XVI) with Ac2O and Sc(OTf)3 gives the diacetate (XVII), which is debenzylated with H2 over Pd/C to yield the primary alcohol (XVIII). The oxidation of (XVIII) with DMP affords the carbaldehyde (XIX), which is finally condensed with iodoform and CrCl2 to furnish the target iodovinyl-tetrahydrofuran intermediate (XX).
| 【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 |
|---|---|---|---|---|---|---|
| (XII) | 46061 | [(2R,3R)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol | C10H18O2 | 详情 | 详情 | |
| (XIII) | 46068 | benzyl [(2S,3S)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methyl ether; (2S,3S)-3-[(benzyloxy)methyl]-2-methyl-2-(4-methyl-3-pentenyl)oxirane | C17H24O2 | 详情 | 详情 | |
| (XIV) | 46069 | (2S,3R)-1-(benzyloxy)-3,7-dimethyl-6-octene-2,3-diol | C17H26O3 | 详情 | 详情 | |
| (XV) | 46070 | (1S,2R)-1-[(benzyloxy)methyl]-2-hydroxy-2,6-dimethyl-5-heptenyl acetate | C19H28O4 | 详情 | 详情 | |
| (XVI) | 46071 | (1S)-2-(benzyloxy)-1-[(2R,5R)-5-(1-hydroxy-1-methylethyl)-2-methyltetrahydro-2-furanyl]ethyl acetate | C19H28O5 | 详情 | 详情 | |
| (XVII) | 46072 | 1-[(2R,5R)-5-[(1S)-1-(acetoxy)-2-(benzyloxy)ethyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C21H30O6 | 详情 | 详情 | |
| (XVIII) | 46073 | 1-[(2R,5R)-5-[(1S)-1-(acetoxy)-2-hydroxyethyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C14H24O6 | 详情 | 详情 | |
| (XIX) | 46074 | (1R)-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-2-oxoethyl acetate | C14H22O6 | 详情 | 详情 | |
| (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 |
合成路线5
该中间体在本合成路线中的序号：(V)The regio- and stereoselective hydrolysis of (2R,3R)-epoxygeraniol (V) with HClO4 in THF/water gives the trihydroxy compound (VI), which is selectively benzoylated with benzoyl chloride, TEA and DMAP to yield the dibenzoate (VII). The reaction of (VII) with TBCO in nitromethane affords a mixture of tetrahydrofuran (VIII) and tetrahydropyran (IX), which are separated by chromatography. The desired isomer (X) is hydrolyzed with K2CO3 in methanol to provide the alpha-diol (XI), which is finally oxidized with NaIO4 in THF/water to furnish the target aldehydic intermediate (IV).
| 【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 |
|---|---|---|---|---|---|---|
| (IV) | 46060 | (2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-carbaldehyde | C9H15BrO2 | 详情 | 详情 | |
| (V) | 46061 | [(2R,3R)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol | C10H18O2 | 详情 | 详情 | |
| (VI) | 46062 | (2R,3S)-3,7-dimethyl-6-octene-1,2,3-triol | C10H20O3 | 详情 | 详情 | |
| (VII) | 46063 | (2R,3S)-2,3-bis(benzoyloxy)-3,7-dimethyl-6-octenyl benzoate | C31H32O6 | 详情 | 详情 | |
| (VIII) | 46064 | (2R)-2-(benzoyloxy)-2-[(2S)-5-(1-bromo-1-methylethyl)-2-methyltetrahydro-2-furanyl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (IX) | 46065 | (1R)-2-(benzoyloxy)-1-[(2S)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (X) | 46066 | (1R)-2-(benzoyloxy)-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]ethyl benzoate | C24H27BrO5 | 详情 | 详情 | |
| (XI) | 46067 | (1R)-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-1,2-ethanediol | C10H19BrO3 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XII)The tetrahydrofuran intermediate (XX) has been obtained as follows: The reaction of (2S,3S)-epoxygeraniol (XII) with Bn-Br and NaH in THF gives the benzyl ether (XIII), which is treated with NaClO4 to yield the diol (XIV). The selective monoacetylation of (XI) with Ac2O and pyridine affords the monoacetate (XV), which is cyclized by means of (CF3CO2)ReO3 and TFAA to provide the tetrahydrofuran (XVI). The acetylation of the tertiary alcohol of (XVI) with Ac2O and Sc(OTf)3 gives the diacetate (XVII), which is debenzylated with H2 over Pd/C to yield the primary alcohol (XVIII). The oxidation of (XVIII) with DMP affords the carbaldehyde (XIX), which is finally condensed with iodoform and CrCl2 to furnish the target iodovinyl-tetrahydrofuran intermediate (XX).
| 【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 |
|---|---|---|---|---|---|---|
| (XII) | 46061 | [(2R,3R)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol | C10H18O2 | 详情 | 详情 | |
| (XIII) | 46068 | benzyl [(2S,3S)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methyl ether; (2S,3S)-3-[(benzyloxy)methyl]-2-methyl-2-(4-methyl-3-pentenyl)oxirane | C17H24O2 | 详情 | 详情 | |
| (XIV) | 46069 | (2S,3R)-1-(benzyloxy)-3,7-dimethyl-6-octene-2,3-diol | C17H26O3 | 详情 | 详情 | |
| (XV) | 46070 | (1S,2R)-1-[(benzyloxy)methyl]-2-hydroxy-2,6-dimethyl-5-heptenyl acetate | C19H28O4 | 详情 | 详情 | |
| (XVI) | 46071 | (1S)-2-(benzyloxy)-1-[(2R,5R)-5-(1-hydroxy-1-methylethyl)-2-methyltetrahydro-2-furanyl]ethyl acetate | C19H28O5 | 详情 | 详情 | |
| (XVII) | 46072 | 1-[(2R,5R)-5-[(1S)-1-(acetoxy)-2-(benzyloxy)ethyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C21H30O6 | 详情 | 详情 | |
| (XVIII) | 46073 | 1-[(2R,5R)-5-[(1S)-1-(acetoxy)-2-hydroxyethyl]-5-methyltetrahydro-2-furanyl]-1-methylethyl acetate | C14H24O6 | 详情 | 详情 | |
| (XIX) | 46074 | (1R)-1-[(2R,5R)-5-[1-(acetoxy)-1-methylethyl]-2-methyltetrahydro-2-furanyl]-2-oxoethyl acetate | C14H22O6 | 详情 | 详情 | |
| (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 |