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【结 构 式】 
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【分子编号】54345 【品名】(1E,3S,5Z)-7-bromo-2,6-dimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-heptadien-3-ol 【CA登记号】n/a |
【 分 子 式 】C13H18BrNOS 【 分 子 量 】316.26206 【元素组成】C 49.37% H 5.74% Br 25.27% N 4.43% O 5.06% S 10.14% |
合成路线1
该中间体在本合成路线中的序号：(XIV)The intermediate phosphonium bromide (XVII) is obtained as follows: The reaction of the glucoside (I) with Me2CuLi in THF gives the methyl derivative (II), which is converted into the unsaturated pyranoside (III). The reductive deoxygenation of (III) with Pd(OAc)2 and NaBH4 affords the acetate (IV), which is treated with NaOMe in methanol to afford the carbinol (V). The oxidation of (V) with oxalyl chloride in DMSO provides the carbaldehyde (VI), which is treated with Me-Mg-Br in THF to give the secondary alcohol (VII). The oxidation of (VII) with oxalyl chloride in DMSO yields the ketone (VIII), which is condensed with the phosphonate (IX) (obtained by reaction of 4-(chloromethyl)-2-methylthiazole (X) with triethyl phosphite (XI) at 165 C) by means of tBu-OK in THF to afford the vinyl-dihydropyran (XII). The opening of the dihydropyran ring of (XII) by means of HOAc in THF/water, followed by reduction of the intermediate aldehyde, provides the unsaturated diol (XIII). The regioselective bromination of (XIII) with CBr4 and PPh3 in acetonitrile gives the bromo derivative (XIV), which is silylated with Tbdms-OTf to yield the silyl ether derivative (XV). Finally, this compound is condensed with methylenetriphenylphosphorane (XVI) in THF to afford the target intermediate, the phosphonium bromide (XVII).
| 【1】 Potier, P.; Ermolenko, M.S.; Synthesis of epothilones B and D from D-glucose. Tetrahedron Lett 2002, 43, 16, 2895. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 54335 | (1aR,2S,3aR,6R,7aS,7bS)-2-methoxy-6-phenylhexahydrooxireno[2',3':4,5]pyrano[3,2-d][1,3]dioxine; (1aR,2S,3aR,6R,7aS,7bS)-6-phenylhexahydrooxireno[2',3':4,5]pyrano[3,2-d][1,3]dioxin-2-yl methyl ether | n/a | C14H16O5 | 详情 | 详情 |
| (II) | 54336 | (2R,4aR,6S,7S,8S,8aS)-6-methoxy-7-methyl-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-ol | n/a | C15H20O5 | 详情 | 详情 |
| (III) | 54337 | [(2R,3S,6S)-3-(acetyloxy)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]methyl acetate | n/a | C12H18O6 | 详情 | 详情 |
| (IV) | 54338 | [(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]methyl acetate | n/a | C10H16O4 | 详情 | 详情 |
| (V) | 54339 | [(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]methanol | n/a | C8H14O3 | 详情 | 详情 |
| (VI) | 54340 | (2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | n/a | C8H12O3 | 详情 | 详情 |
| (VII) | 54341 | (1R)-1-[(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]-1-ethanol | n/a | C9H16O3 | 详情 | 详情 |
| (VIII) | 54342 | 1-[(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]-1-ethanone | n/a | C9H14O3 | 详情 | 详情 |
| (IX) | 44442 | diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C9H16NO3PS | 详情 | 详情 | |
| (X) | 40819 | 4-(chloromethyl)-2-methyl-1,3-thiazole | C5H6ClNS | 详情 | 详情 | |
| (XII) | 54343 | 4-{(E)-2-[(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]-1-propenyl}-2-methyl-1,3-thiazole; methyl (2S,6S)-3-methyl-6-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5,6-dihydro-2H-pyran-2-yl ether | n/a | C14H19NO2S | 详情 | 详情 |
| (XIII) | 54344 | (2Z,5S,6E)-2,6-dimethyl-7-(2-methyl-1,3-thiazol-4-yl)-2,6-heptadiene-1,5-diol | n/a | C13H19NO2S | 详情 | 详情 |
| (XIV) | 54345 | (1E,3S,5Z)-7-bromo-2,6-dimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-heptadien-3-ol | n/a | C13H18BrNOS | 详情 | 详情 |
| (XV) | 46147 | 4-((1E,3S,5Z)-7-bromo-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-1,5-heptadienyl)-2-methyl-1,3-thiazole; (1S,3Z)-5-bromo-4-methyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl tert-butyl(dimethyl)silyl ether | C19H32BrNOSSi | 详情 | 详情 | |
| (XVI) | 27301 | methylene(triphenyl)phosphorane | C19H17P | 详情 | 详情 | |
| (XVII) | 46148 | [(3Z,6S,7E)-6-[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-8-(2-methyl-1,3-thiazol-4-yl)-3,7-octadienyl](triphenyl)phosphonium bromide | C38H49BrNOPSSi | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIV)The intermediate phosphonium bromide (XVII) is obtained as follows: The reaction of the glucoside (I) with Me2CuLi in THF gives the methyl derivative (II), which is converted into the unsaturated pyranoside (III). The reductive deoxygenation of (III) with Pd(OAc)2 and NaBH4 affords the acetate (IV), which is treated with NaOMe in methanol to afford the carbinol (V). The oxidation of (V) with oxalyl chloride in DMSO provides the carbaldehyde (VI), which is treated with Me-Mg-Br in THF to give the secondary alcohol (VII). The oxidation of (VII) with oxalyl chloride in DMSO yields the ketone (VIII), which is condensed with the phosphonate (IX) (obtained by reaction of 4-(chloromethyl)-2-methylthiazole (X) with triethyl phosphite (XI) at 165 C) by means of tBu-OK in THF to afford the vinyl-dihydropyran (XII). The opening of the dihydropyran ring of (XII) by means of AcOH in THF/water, followed by reduction of the intermediate aldehyde, provides the unsaturated diol (XIII). The regioselective bromination of (XIII) with CBr4 and PPh3 in acetonitrile gives the bromo derivative (XIV), which is silylated with Tbdms-OTf to yield the silyl ether derivative (XV). Finally, this compound is condensed with methylenetriphenylphosphorane (XVI) in THF to afford the target intermediate, the phosphonium bromide (XVII).
| 【1】 Potier, P.; Ermolenko, M.S.; Synthesis of epothilones B and D from D-glucose. Tetrahedron Lett 2002, 43, 16, 2895. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 54335 | (1aR,2S,3aR,6R,7aS,7bS)-2-methoxy-6-phenylhexahydrooxireno[2',3':4,5]pyrano[3,2-d][1,3]dioxine; (1aR,2S,3aR,6R,7aS,7bS)-6-phenylhexahydrooxireno[2',3':4,5]pyrano[3,2-d][1,3]dioxin-2-yl methyl ether | n/a | C14H16O5 | 详情 | 详情 |
| (II) | 54336 | (2R,4aR,6S,7S,8S,8aS)-6-methoxy-7-methyl-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-ol | n/a | C15H20O5 | 详情 | 详情 |
| (III) | 54337 | [(2R,3S,6S)-3-(acetyloxy)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]methyl acetate | n/a | C12H18O6 | 详情 | 详情 |
| (IV) | 54338 | [(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]methyl acetate | n/a | C10H16O4 | 详情 | 详情 |
| (V) | 54339 | [(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]methanol | n/a | C8H14O3 | 详情 | 详情 |
| (VI) | 54340 | (2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | n/a | C8H12O3 | 详情 | 详情 |
| (VII) | 54341 | (1R)-1-[(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]-1-ethanol | n/a | C9H16O3 | 详情 | 详情 |
| (VIII) | 54342 | 1-[(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]-1-ethanone | n/a | C9H14O3 | 详情 | 详情 |
| (IX) | 44442 | diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C9H16NO3PS | 详情 | 详情 | |
| (X) | 40819 | 4-(chloromethyl)-2-methyl-1,3-thiazole | C5H6ClNS | 详情 | 详情 | |
| (XII) | 54343 | 4-{(E)-2-[(2S,6S)-6-methoxy-5-methyl-3,6-dihydro-2H-pyran-2-yl]-1-propenyl}-2-methyl-1,3-thiazole; methyl (2S,6S)-3-methyl-6-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-5,6-dihydro-2H-pyran-2-yl ether | n/a | C14H19NO2S | 详情 | 详情 |
| (XIII) | 54344 | (2Z,5S,6E)-2,6-dimethyl-7-(2-methyl-1,3-thiazol-4-yl)-2,6-heptadiene-1,5-diol | n/a | C13H19NO2S | 详情 | 详情 |
| (XIV) | 54345 | (1E,3S,5Z)-7-bromo-2,6-dimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5-heptadien-3-ol | n/a | C13H18BrNOS | 详情 | 详情 |
| (XV) | 46147 | 4-((1E,3S,5Z)-7-bromo-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-1,5-heptadienyl)-2-methyl-1,3-thiazole; (1S,3Z)-5-bromo-4-methyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl tert-butyl(dimethyl)silyl ether | C19H32BrNOSSi | 详情 | 详情 | |
| (XVI) | 27301 | methylene(triphenyl)phosphorane | C19H17P | 详情 | 详情 | |
| (XVII) | 46148 | [(3Z,6S,7E)-6-[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-8-(2-methyl-1,3-thiazol-4-yl)-3,7-octadienyl](triphenyl)phosphonium bromide | C38H49BrNOPSSi | 详情 | 详情 |