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【结 构 式】 
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【分子编号】56637 【品名】(E)-3-phenyl-2-propenyl (1R,2S)-4-methylene-2-{[({[(E)-3-phenyl-2-propenyl]oxy}carbonyl)amino]carbonyl}cyclopentanecarboxylate 【CA登记号】 |
【 分 子 式 】C27H27NO5 【 分 子 量 】445.51512 【元素组成】C 72.79% H 6.11% N 3.14% O 17.96% |
合成路线1
该中间体在本合成路线中的序号：(XXII)Cyclization of the tetracarboxylic acid (XV) gives 4-oxocyclopentane-1,2-dicarboxylic acid (XVI), which is esterified with ethanol and sulfuric acid to yield the diester (XVII). Reaction of diester (XVII) with methyl-(triphenyl)phosphonium bromide and t-BuOK in THF affords 4-methylenecyclopentane-1,2-dicarboxylic acid diethyl ester (XVIII), which is hydrolyzed with KOH in THF/water to provide the corresponding free acid (XIX). The anhydrization of (XIX) by means of propionic anhydride at 135 C gives anhydride (III), which is submitted to an enantioselective quinine-mediated alcoholysis with 3-phenyl-2-propen-1-ol (XX) to yield (1R,2S)-2-amino-4-methylenecyclopentane-1-carboxylic acid 3-phenyl-2-propenyl monoester (XXI). Degradation of the free carboxylic acid group of (XXI) by means of DPPA, TEA and alcohol (XX) in hot toluene affords carbamate (XXII), which is finally fully deprotected with Pd(OAc)2 and PPh3 in ethanol.
| 【1】 Mittendorf, J.; Kunisch, F.; Matzke, M.; Militzer, H.-C.; Schmidt, A.; Schonfeld, W.; Novel antifungal beta-amino acids: Synthesis and activity against Candida albicans. Bioorg Med Chem Lett 2003, 13, 3, 433. |
| 【2】 Sorbera, L.A.; Castañer, J.; Bozzo, J.; PLD-118. Drugs Fut 2002, 27, 11, 1049. |
| 【3】 Schoenfeld, W.; Discovery, synthesis and SAR of beta-amino acid BAY 10-888/PLD-118, a novel antifungal for treatment of yeast infections. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-811. |
| 【4】 Mittendorf, J. (Bayer AG); Efficient and highly enantioselective process for the preparation of enantiomerically pure cyclopentane-beta-amino acids . EP 0805145 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 56629 | (3aR,6aS)-5-methylenetetrahydro-1H-cyclopenta[c]furan-1,3(3aH)-dione | C8H8O3 | 详情 | 详情 | |
| (XV) | 56634 | 1,2,3,4-butanetetracarboxylic acid;1,2,3,4-Tetracarboxybutane | 1703-58-8 | C8H10O8 | 详情 | 详情 |
| (XVI) | 56635 | 4-oxo-1,2-cyclopentanedicarboxylic acid | C7H8O5 | 详情 | 详情 | |
| (XVII) | 56636 | diethyl 4-oxo-1,2-cyclopentanedicarboxylate | C11H16O5 | 详情 | 详情 | |
| (XVIII) | 56638 | diethyl 4-methylene-1,2-cyclopentanedicarboxylate | C12H18O4 | 详情 | 详情 | |
| (XIX) | 56639 | 4-methylene-1,2-cyclopentanedicarboxylic acid | C8H10O4 | 详情 | 详情 | |
| (XX) | 13951 | (E)-3-Phenyl-2-propen-1-ol | 104-54-1 | C9H10O | 详情 | 详情 |
| (XXI) | 27283 | (1S,2R)-4-methylene-2-([[(E)-3-phenyl-2-propenyl]oxy]carbonyl)cyclopentanecarboxylic acid | C17H18O4 | 详情 | 详情 | |
| (XXII) | 56637 | (E)-3-phenyl-2-propenyl (1R,2S)-4-methylene-2-{[({[(E)-3-phenyl-2-propenyl]oxy}carbonyl)amino]carbonyl}cyclopentanecarboxylate | C27H27NO5 | 详情 | 详情 |