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【结 构 式】 
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【药物名称】Dehydroepiandrosterone, Prasterone, PB-007, EL-10, DHEA, GL-701, Fidelin, Anastar, Prestara, Inflabloc, Aslera 【化学名称】3beta-Hydroxyandrost-5-en-17-one 【CA登记号】53-43-0 【 分 子 式 】C19H28O2 【 分 子 量 】288.43381 |
【开发单位】Genelabs (Proprietary), Genelabs (Orphan Drug), Paladin (Orphan Drug), Jenapharm (Originator), Stanford University (Originator), Mipharm (Licensee), Pharmadigm (Licensee), Tanabe Seiyaku (Licensee), Watson (Licensee) 【药理作用】Acute Myocardial Infarction, Treatment of, Adrenocortical Dysfunction Therapy, CARDIOVASCULAR DRUGS, Cerebrovascular Diseases, Treatment of, ENDOCRINE DRUGS, IMMUNOMODULATING AGENTS, Immunosuppressants, NEUROLOGIC DRUGS, Stroke, Treatment of, Systemic Lupus Erythematosus, Agents for, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Treatment of Other Autoimmune Disorders |
合成路线1
Prasterone can be obtained by two related ways: 1) The acetylation of cholesterol (I) with refluxing acetic anhydride gives the corresponding acetate (II), which is brominated with Br2 in acetic acid to the dibromide (III). The oxidation of (III) with CrO3 in acetic acid followed by debromination with Zn in the same solvent and treatment with semicarbazide and sodium acetate in ethanol/water affords 3beta-acetoxyandrost-5-en-17-one semicarbazone (IV), which is finally hydrolyzed with 5N H2SO4 in refluxing ethanol. 2) The partial silylation of androst-5-ene-3beta,17beta-diol (V) with tert-butyldimethylsilyl chloride and imidazole in DMF yields the 3beta-silyloxy derivative (VI), which is oxidized with CrO3-pyridine complex in pyridine affording 3-(tert-butyldimethylsilyloxy)androst-5-en-17-one (VII). Finally, this compound is deprotected with hot acetic acid/water/THF or with tetrabutylammonium fluoride in THF.
| 【1】 Fernholz, E.; Wallis, E.S.; The preparation of dehydroandrosterone from cholesterol. J Am Chem Soc 1935, 57, 1504-6. |
| 【2】 Castañer, J.; Mealy, N.; Rabasseda, X.; Prasterone. Drugs Fut 1995, 20, 6, 575. |
| 【3】 Ruzicka, L.; Wettstein, A.; Sexual hormones: Synthetic preparation of the male sexual hormones trans-dehydroandrosterone and androstene-3,17-dione. Helv Chim Acta 1935, 18, 986-95. |
| 【4】 Fernholz, E.; Wallis, E.S.; The constitution of dehydro-androsterone and its preparation from cholesterol. J Am Chem Soc 1935, 57, 1379-80. |
| 【5】 Hosoda, H.; Fishman, J.; Fukushima, D.K.; Convenient, high yield conversion of androst-5-ene-3beta,17beta-diol to dehydroisoandrosterone. J Org Chem 1973, 38, 24, 4209-11. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 32057 | tert-butyl(chloro)dimethylsilane | 18162-48-6 | C6H15ClSi | 详情 | 详情 | |
| (I) | 16812 | (+)-Cholesterol; (+)-(3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol | 14868-17-8 | C27H46O | 详情 | 详情 |
| (II) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (III) | 16814 | (3S,8S,9S,10R,13R,14S,17R)-5,6-dibromo-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C29H48Br2O2 | 详情 | 详情 | |
| (IV) | 16815 | (3S,8R,9S,10R,13S,14S)-17-[(E)-2-(aminocarbonyl)hydrazono]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H33N3O3 | 详情 | 详情 | |
| (V) | 16816 | (3S,8R,9S,10R,13S,14S,17S)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol; 3beta,17beta-Dihydroxyandrost-5-ene; 5-Androstene-3beta,17beta-diol | 521-17-5 | C19H30O2 | 详情 | 详情 |
| (VI) | 16817 | (3S,8R,9S,10R,13S,14S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol | C25H44O2Si | 详情 | 详情 | |
| (VII) | 16818 | (3S,8R,9S,10R,13S,14S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C25H42O2Si | 详情 | 详情 |