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【结 构 式】 
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【分子编号】54266 【品名】(1S,2E)-1-(1,3-dithian-2-ylmethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl acetate 【CA登记号】 |
【 分 子 式 】C15H21NO2S3 【 分 子 量 】343.53528 【元素组成】C 52.44% H 6.16% N 4.08% O 9.31% S 28% |
合成路线1
该中间体在本合成路线中的序号：(IX)The omega iodoalkyl thiazole intermediate (XII) is obtained as follows: The cyclization of 2-hydroxypropionaldehyde dimethyl acetal (I) with acetaldehyde (II) by means of warm Dowex (H+) and catalyzed by 2-deoxyribose-5-phosphate aldolase (DERA) gives the chiral tetrahydrofuran derivative (III), which is acylated with Ac-Cl and pyridine to yield the acetoxy compound (IV). The reaction of (IV) with BF3/Et2O, propane-1,3-dithiol (V) and TiCl4 affords the protected dithiane (VI), which is oxidized with oxalyl chloride in DMSO to provide the ketone (VII). The Wittig condensation of (VII) with phosphine oxide (VIII) by means of BuLi in THF provides the protected alkyl thiazole (IX), which is treated with HgClO4 to cleave the dithiane ring and yield carbaldehyde (X). Finally, this aldehyde is coupled with iodomethylenephosphorane (XI) by means of NaHMDS in THF/HMPA to afford the target omega iodoalkyl thiazole intermediate (XII).
| 【1】 Wong, C.-H.; Liu, J.; Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem. Int Ed 2002, 41, 8, 1404. |
| 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) | 54261 | 1,1-dimethoxy-2-propanol | 42919-42-6 | C5H12O3 | 详情 | 详情 |
| (II) | 11974 | Acetaldehyde | 75-07-0 | C2H4O | 详情 | 详情 |
| (III) | 54262 | (4S,5R)-5-methyltetrahydro-2,4-furandiol | C5H10O3 | 详情 | 详情 | |
| (IV) | 54263 | (2R,3S)-5-hydroxy-2-methyltetrahydro-3-furanyl acetate | n/a | C7H12O4 | 详情 | 详情 |
| (V) | 29729 | 1,3-propanedithiol; 3-sulfanylpropylhydrosulfide | 109-80-8 | C3H8S2 | 详情 | 详情 |
| (VI) | 54264 | (1S,2R)-1-(1,3-dithian-2-ylmethyl)-2-hydroxypropyl acetate | n/a | C10H18O3S2 | 详情 | 详情 |
| (VII) | 54265 | (1S)-1-(1,3-dithian-2-ylmethyl)-2-oxopropyl acetate | C10H16O3S2 | 详情 | 详情 | |
| (VIII) | 47000 | (2-methyl-1,3-thiazol-4-yl)methyl(diphenyl)phosphine oxide; 4-[(diphenylphosphoryl)methyl]-2-methyl-1,3-thiazole | C17H16NOPS | 详情 | 详情 | |
| (IX) | 54266 | (1S,2E)-1-(1,3-dithian-2-ylmethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl acetate | C15H21NO2S3 | 详情 | 详情 | |
| (X) | 44531 | (1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate | C12H15NO3S | 详情 | 详情 | |
| (XI) | 44532 | (iodomethylene)(triphenyl)phosphorane | C19H16IP | 详情 | 详情 | |
| (XII) | 44493 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate | C13H16INO2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The omega iodoalkyl thiazole intermediate (XII) is obtained as follows: The cyclization of 2-hydroxypropionaldehyde dimethyl acetal (I) with acetaldehyde (II) by means of warm Dowex (H+) and catalyzed by 2-deoxyribose-5-phosphate aldolase (DERA) gives the chiral tetrahydrofuran derivative (III), which is acylated with Ac-Cl and pyridine to yield the acetoxy compound (IV). The reaction of (IV) with BF3/Et2O, propane-1,3-dithiol (V) and TiCl4 affords the protected dithiane (VI), which is oxidized with oxalyl chloride in DMSO to provide the ketone (VII). The Wittig condensation of (VII) with phosphine oxide (VIII) by means of BuLi in THF provides the protected alkyl thiazole (IX), which is treated with HgClO4 to cleave the dithiane ring and yield carbaldehyde (X). Finally, this aldehyde is coupled with iodomethylenephosphorane (XI) by means of NaHMDS in THF/HMPA to afford the target omega iodoalkyl thiazole intermediate (XII).
| 【1】 Wong, C.-H.; Liu, J.; Aldolase-catalyzed asymmetric synthesis of novel pyranose synthons as a new entry to heterocycles and epothilones. Angew Chem. Int Ed 2002, 41, 8, 1404. |
| 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) | 54261 | 1,1-dimethoxy-2-propanol | 42919-42-6 | C5H12O3 | 详情 | 详情 |
| (II) | 11974 | Acetaldehyde | 75-07-0 | C2H4O | 详情 | 详情 |
| (III) | 54262 | (4S,5R)-5-methyltetrahydro-2,4-furandiol | C5H10O3 | 详情 | 详情 | |
| (IV) | 54263 | (2R,3S)-5-hydroxy-2-methyltetrahydro-3-furanyl acetate | n/a | C7H12O4 | 详情 | 详情 |
| (V) | 29729 | 1,3-propanedithiol; 3-sulfanylpropylhydrosulfide | 109-80-8 | C3H8S2 | 详情 | 详情 |
| (VI) | 54264 | (1S,2R)-1-(1,3-dithian-2-ylmethyl)-2-hydroxypropyl acetate | n/a | C10H18O3S2 | 详情 | 详情 |
| (VII) | 54265 | (1S)-1-(1,3-dithian-2-ylmethyl)-2-oxopropyl acetate | C10H16O3S2 | 详情 | 详情 | |
| (VIII) | 47000 | (2-methyl-1,3-thiazol-4-yl)methyl(diphenyl)phosphine oxide; 4-[(diphenylphosphoryl)methyl]-2-methyl-1,3-thiazole | C17H16NOPS | 详情 | 详情 | |
| (IX) | 54266 | (1S,2E)-1-(1,3-dithian-2-ylmethyl)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl acetate | C15H21NO2S3 | 详情 | 详情 | |
| (X) | 44531 | (1S,2E)-2-methyl-3-(2-methyl-1,3-thiazol-4-yl)-1-(2-oxoethyl)-2-propenyl acetate | C12H15NO3S | 详情 | 详情 | |
| (XI) | 44532 | (iodomethylene)(triphenyl)phosphorane | C19H16IP | 详情 | 详情 | |
| (XII) | 44493 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-butenyl acetate | C13H16INO2S | 详情 | 详情 |