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【结 构 式】 
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【分子编号】24235 【品名】3-[(7aS)-7a-methyl-1,5-dioxo-2,3,5,6,7,7a-hexahydro-1H-inden-4-yl]propionic acid 【CA登记号】 |
【 分 子 式 】C13H16O4 【 分 子 量 】236.26764 【元素组成】C 66.09% H 6.83% O 27.09% |
合成路线1
该中间体在本合成路线中的序号：(V)The cyclization of methyl 5-oxo-6-heptenoate (I) with 2-methylcyclopentane-1-3-dione (II) by means of pyridine in refluxing toluene gives methyl 3-(1,5-dioxo-7a-methyl 5,6,7,7a-tetrahydroindan-4-yl)propionate (III), which is hydrolyzed with 5N HCl to the corresponding free acid (IV). Separation of the optical isomers with ephedrine affords the 3-(1,5-dioxo-7a-methyl-5,6,7,7a-tetrahydroindan 4-yl)propionic acid (V), which is reduced with NaBH4 in water to the 1beta-hydroxyacid (VI). Reduction of the double bond of (VI) with H2 over Pd/C in acetic acid gives the saturated ketoacid (VII), which is acetylated with acetic anhydride to the acetoxy Iactone (VIII). The Grignard reaction of (VIII) with propylmagnesium bromide (IX) and treatment with methanolic KOH affords 6-ethyl-3-hydroxy-3a-methyl-1,2,3,3a,4,5,8,9,9a,9b decahydro 7H benz[e]inden-7-one (X), which is finally acetylated with acetic anhydride as before.
| 【1】 Joly, R.; Warnant, J.; Goffinet, B.; Nouveaux composés tricycliques et procédé de préparation. FR 1359675 . |
| 【2】 Amiard, G.; Torelli, V.; Nomine, G.; Sur l'hydrogenation catalytique de structures tetrahydroindaniques, intermediaries de syntheses totales steroides. Bull Soc Chim France 1968, 9, 2, 3664. |
| 【3】 Cerede, J.; Amiard, G.; Velluz, L.; Nomine, G.; Torelli, V.; Pogres en synthese totale steroide. CR Hebd Seances Acad Sci 1963, 257, 3086. |
| 【4】 Morales-Alanis, H.; et al.; Antiandrogenic activity of a series of des-A-steroid derivatives. J Med Chem 1985, 28, 12, 1796. |
| 【5】 Bouton, M.-M.; Jacques, J.; Pierdet, A. (Aventis Pharma SA); Certain decahydro-7H-benz(e)-inden-7-ones, compositions containing same and method of use. EP 0059146; FR 2500441; JP 2243646; JP 57156430; US 4466971; US 4607054; US 4849454; US 4927975; US 5158981 . |
| 【6】 Castaner, J.; Prous, J.; RU-38882. Drugs Fut 1986, 11, 10, 856. |
| 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) | 24231 | methyl 5-oxo-6-heptenoate | C8H12O3 | 详情 | 详情 | |
| (II) | 24232 | 2-methyl-1,3-cyclopentanedione | 765-69-5 | C6H8O2 | 详情 | 详情 |
| (III) | 24233 | methyl 3-(7a-methyl-1,5-dioxo-2,3,5,6,7,7a-hexahydro-1H-inden-4-yl)propanoate | C14H18O4 | 详情 | 详情 | |
| (IV) | 24234 | 3-(7a-methyl-1,5-dioxo-2,3,5,6,7,7a-hexahydro-1H-inden-4-yl)propionic acid | C13H16O4 | 详情 | 详情 | |
| (V) | 24235 | 3-[(7aS)-7a-methyl-1,5-dioxo-2,3,5,6,7,7a-hexahydro-1H-inden-4-yl]propionic acid | C13H16O4 | 详情 | 详情 | |
| (VI) | 24236 | 3-[(1S,7aS)-1-hydroxy-7a-methyl-5-oxo-2,3,5,6,7,7a-hexahydro-1H-inden-4-yl]propionic acid | C13H18O4 | 详情 | 详情 | |
| (VII) | 24237 | 3-[(1S,3aS,4S,7aS)-1-hydroxy-7a-methyl-5-oxooctahydro-1H-inden-4-yl]propionic acid | C13H20O4 | 详情 | 详情 | |
| (VIII) | 24238 | (6aS,7S,9aS,9bS)-6a-methyl-3-oxododecahydrocyclopenta[f]chromen-7-yl acetate | C15H22O4 | 详情 | 详情 | |
| (IX) | 24239 | bromo(ethyl)magnesium；ethylmagnesium bromide | 925-90-6 | C2H5BrMg | 详情 | 详情 |
| (X) | 24240 | (3S,3aS,9aS,9bS)-6-ethyl-3-hydroxy-3a-methyl-1,2,3,3a,4,5,8,9,9a,9b-decahydro-7H-cyclopenta[a]naphthalen-7-one | C16H24O2 | 详情 | 详情 |