【结 构 式】 |
【分子编号】37804 【品名】methyl (2R,3S)-2-(benzoylamino)-3-hydroxy-4-methylpentanoate 【CA登记号】 |
【 分 子 式 】C14H19NO4 【 分 子 量 】265.3092 【元素组成】C 63.38% H 7.22% N 5.28% O 24.12% |
合成路线1
该中间体在本合成路线中的序号:(XVII)On the other hand, Wittig condensation of isobutyraldehyde (X) with methyl (triphenylphosphoranylidene)acetate (XI) afforded (E)-4-methylpent-2-enoic acid methyl ester (XII). Sharpless catalytic asymmetric dihydroxylation of (XII) gave diol (XIII). Condensation of diol (XIII) with trimethyl orthobenzoate in the presence of BF3.Et2O, followed by treatment of the crude cyclic orthoester with acetyl bromide produced bromo ester (XIV). The required alpha-amino group was then introduced by nucleophilic displacement of the bromide of (XIV) with NaN3 in DMSO, followed by catalytic hydrogenation of the resulting azide (XV). The intermediate amino ester (XVI) was then rearranged to hydroxy amide (XVII) upon refluxing in EtOAc. Cyclization of (XVII) to the required trans oxazoline (XVIII) was then achieved by treatment with p-toluenesulfonic acid in boiling toluene.
【1】 Soucy, F.; et al.; A novel and efficient synthesis of a highly active analogue clasto-lactacystin beta-lactone. J Am Chem Soc 1999, 121, 43, 9967. |
【2】 Plamondon, L.; Soucy, F.; Behnke, M.; Roush, W.; Synthesis of clasto-lactacystin beta-lactone and analogs thereof. WO 9909006 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(X) | 13226 | 2-Methylpropanal; Isobutyraldehyde | 78-84-2 | C4H8O | 详情 | 详情 |
(XI) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane;Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
(XII) | 37799 | methyl (E)-4-methyl-2-pentenoate | C7H12O2 | 详情 | 详情 | |
(XIII) | 37800 | methyl (2S,3R)-2,3-dihydroxy-4-methylpentanoate | C7H14O4 | 详情 | 详情 | |
(XIV) | 37801 | (1S,2S)-2-bromo-1-isopropyl-3-methoxy-3-oxopropyl benzoate | C14H17BrO4 | 详情 | 详情 | |
(XV) | 37802 | (1S,2R)-2-azido-1-isopropyl-3-methoxy-3-oxopropyl benzoate | C14H17N3O4 | 详情 | 详情 | |
(XVI) | 37803 | (1S,2R)-2-amino-1-isopropyl-3-methoxy-3-oxopropyl benzoate | C14H19NO4 | 详情 | 详情 | |
(XVII) | 37804 | methyl (2R,3S)-2-(benzoylamino)-3-hydroxy-4-methylpentanoate | C14H19NO4 | 详情 | 详情 | |
(XVIII) | 37805 | methyl (4R,5S)-5-isopropyl-2-phenyl-4,5-dihydro-1,3-oxazole-4-carboxylate | C14H17NO3 | 详情 | 详情 |