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【结 构 式】 
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【分子编号】19512 【品名】(2S,3aR,7aS)octahydro-1H-indole-2-carboxylic acid 【CA登记号】145438-94-4 |
【 分 子 式 】C9H15NO2 【 分 子 量 】169.22364 【元素组成】C 63.88% H 8.93% N 8.28% O 18.91% |
合成路线1
该中间体在本合成路线中的序号：(I)The esterification of (3aR,7aS)-octahydroindole-2(S)-carboxylic acid (I) with benzyl alcohol (II) by means of SOCl2 gives the corresponding benzyl ester (III), which is condensed with N-[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine (IV) by means of 1-hydroxybenzotriazole, N-ethylmorpholine and dicyclohexylcarbodiimide (DCC) in DMF giving the benzyl ester (V) of the desired product. Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol.
| 【1】 Ubach, H.; Henning, R.; Teetz, V.; Geiger, R.; Becker, R.; Gaul, H. (Aventis SA); Novel bicyclic amino acid derivs., process for their preparation and their use , as well as bicyclic amino acids as intermediates and process for their preparation. DE 3151690; EP 0084164; EP 0170775; JP 1989301659; JP 1989301695 . |
| 【2】 Prous, J.; Castaner, J.; TRANDOLAPRIL < Rec INN >. Drugs Fut 1989, 14, 8, 778. |
| 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) | 19512 | (2S,3aR,7aS)octahydro-1H-indole-2-carboxylic acid | 145438-94-4 | C9H15NO2 | 详情 | 详情 |
| (II) | 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 |
| (III) | 19514 | benzyl (2S,3aR,7aS)octahydro-1H-indole-2-carboxylate | 144540-71-6 | C16H21NO2 | 详情 | 详情 |
| (IV) | 11360 | (2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]propionic acid; (S)-N-(1-Ethoxycarbonyl-3-phenylpropyl)-(S)-alanine | 82717-96-2 | C15H21NO4 | 详情 | 详情 |
| (V) | 19516 | benzyl (2S,3aR,7aS)-1-((2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)octahydro-1H-indole-2-carboxylate | 98677-37-3 | C31H40N2O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The cyclization of phloroglucinol (I) with 3-oxohexanoic acid methyl ester (II) by means of conc. sulfuric acid gives the benzopyranone (III), which is acylated with 2-methyl-2-butenoyl chloride (IV) and AlCl3 in dichloroethane to yield the 5-hydroxy-7-(2-methyl-2-butenoyloxy)-4-propylbenzopyran-2-one (V). This compound, without isolation, rearranges under the reaction conditions to afford 5,7-dihydroxy-8-(2-methyl-2-butenoyloxy)-4-propylbenzopyran-2-one (VI). The cyclization of (VI) with 3-methyl-2-butenal (VII) in refluxing pyridine provides the benzo-tripyran-2,12-dione derivative (VIII) -alternatively, conversion of (VI) into (VIII) can be performed by first cyclization of (VI) by means of TEA to furnish compound (IX), which is then subjected to cyclization with 3-methyl-2-butenal (VII)-. Finally, reduction of (VIII) with LiAlH(OBu)3 in THF provides the target calanolide A.
| 【1】 Terashima, S.; Koyakumaru, K. (Kuraray Co., Ltd.; Sagami Chemical Research Center); Processes for preparing calanolide A and intermediates thereof. JP 2002193971; WO 0251847 . |
| 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) | 11799 | 1,3,5-Benzenetriol; Fluoroglucinol | 108-73-6 | C6H6O3 | 详情 | 详情 |
| (II) | 12516 | ethyl 3-oxohexanoate; ethyl butyrylacetate | 3249-68-1 | C8H14O3 | 详情 | 详情 |
| (III) | 22405 | 5,7-dihydroxy-4-propyl-2H-chromen-2-one | C12H12O4 | 详情 | 详情 | |
| (IV) | 45730 | Tigloyl chloride; (E)-2-methyl-2-butenoyl chloride | 35660-94-7 | C5H7ClO | 详情 | 详情 |
| (V) | 56901 | 5-hydroxy-2-oxo-4-propyl-2H-chromen-7-yl (E)-2-methyl-2-butenoate | C17H18O5 | 详情 | 详情 | |
| (VI) | 56902 | 5,7-dihydroxy-8-[(E)-2-methyl-2-butenoyl]-4-propyl-2H-chromen-2-one | C17H18O5 | 详情 | 详情 | |
| (VII) | 19512 | (2S,3aR,7aS)octahydro-1H-indole-2-carboxylic acid | 145438-94-4 | C9H15NO2 | 详情 | 详情 |
| (VIII) | 22410 | (10R,11R)-6,6,10,11-tetramethyl-4-propyl-10,11-dihydro-2H,6H,12H-dipyrano[2,3-f:2,3-h]chromene-2,12-dione | C22H24O5 | 详情 | 详情 | |
| (IX) | 56903 | (8R,9R)-5-hydroxy-8,9-dimethyl-4-propyl-8,9-dihydro-2H,10H-pyrano[2,3-f]chromene-2,10-dione | C17H18O5 | 详情 | 详情 |