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【结 构 式】 
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【药物名称】EpiBr, HE-2000, Immunitin, Inactivin 【化学名称】16alpha-Bromoepiandrosterone 【CA登记号】28507-02-0 【 分 子 式 】C19H29BrO2 【 分 子 量 】369.34578 |
【开发单位】Colthurst (Originator), Hollis-Eden (Originator), Edenland (Codevelopment) 【药理作用】AIDS Medicines, Anti-Hepatitis B Virus Drugs, Anti-Hepatitis C Virus Drugs, Anti-Hepatitis Virus Drugs, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Antimalarials, Antimycobacterial Agents, Antiviral Drugs, Cystic Fibrosis, Treatment of , IMMUNOMODULATING AGENTS, Immunomodulators, RESPIRATORY DRUGS, Treatment of Protozoal Diseases, Treatment of Tuberculosis |
合成路线1
Epiandrosterone (I) was converted to the oximino ketone (II) by nitrosation with isoamyl nitrite in the presence of potassium tert-butoxide. Reaction of (II) with sodium hypochlorite and ammonia gave rise to the diazo ketone (III), which, upon treatment with HBr, afforded the title 16-alpha-bromo derivative
| 【1】 Abou-Gharbia, M.; et al.; Synthesis of dehydroepiandrosterone sulfatide and 16alpha-halogenated steroids. J Pharm Sci 1981, 70, 10, 1154. |
| 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) | 62421 | (3S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethylhexadecahydro-17H-cyclopenta[a]phenanthren-17-one | 481-29-8 | C19H30O2 | 详情 | 详情 |
| (II) | 62422 | (3S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyldodecahydro-1H-cyclopenta[a]phenanthrene-16,17(2H,6H)-dione 16-oxime | C19H29NO3 | 详情 | 详情 | |
| (III) | 62423 | C19H28N2O2 | 详情 | 详情 |
合成路线2
Alternatively, the title compound was directly obtained by bromination of epiandrosterone (I) with cupric bromide in refluxing MeOH
| 【1】 Abou-Gharbia, M.; et al.; Synthesis of dehydroepiandrosterone sulfatide and 16alpha-halogenated steroids. J Pharm Sci 1981, 70, 10, 1154. |
| 【2】 Han, M.C.; Hayes B.A.; Prendergast, P.T.; Gupta, S.; Inhibition of HIV replication: Synthesis of [4-14C]-5alpha-androstan-16alpha-bromo-3 beta-ol-17-one. J Label Compd Radiopharm 2000, 43, 12, 1149. |
合成路线3
The reaction of testosterone (I) with isobutylene (II) in dichloromethane catalyzed by trifluoromethanesulfonic acid gives the tert-butyl ether (III), which is ozonolyzed with O3 and H2O2 in AcOH/ethyl acetate to yield the seco-steroid (IV). The cyclization of (IV) by means of acetic anhydride and potassium acetate at 135 C affords the 4-oxa steroid (V), which is methylated with 14C-labeled methylmagnesium iodide in ether to provide the intermediate (VI). The rearrangement of (VI) by means of NaOH in ethanol gives the labeled testosterone tert-butyl ether (VII), which is deprotected by means of 6N HCl in refluxing ethanol to yield the labeled testosterone (VIII). The reduction of the double bond of (VIII) with Li in liquid ammonia affords the dihydro compound (IX), which is oxidized with Jones oxidant in acetone to provide the labeled androstane-3.17-dione (X). The selective reduction of the 3-oxo group of (X) by means of tri-tert-butoxy lithium aluminum hydride in hot THF gives the labeled 3-beta-hydroxyandrostan-17-one (XI), which is brominated with CuBr2 in refluxing methanol to yield the target alpha-bromo derivative, along with some beta-isomer that is separated by column chromatography
| 【1】 Han, M.C.; Hayes B.A.; Prendergast, P.T.; Gupta, S.; Inhibition of HIV replication: Synthesis of [4-14C]-5alpha-androstan-16alpha-bromo-3 beta-ol-17-one. J Label Compd Radiopharm 2000, 43, 12, 1149. |
| 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) | 54210 | 17beta-Hydroxyandrost-4-en-3-one; 4-Androsten-17-beta-ol-3-one; Android; Androlin; delta4-Androsten-17beta-ol-3-one; Halotensin; Oreton; Testex; Testoderm; Testosterone; Testred; Virilon | 58-22-0 | C19H28O2 | 详情 | 详情 |
| (II) | 15926 | 2-methyl-1-propene; isobutylene | 115-11-7 | C4H8 | 详情 | 详情 |
| (III) | 62424 | (10R,13S,17S)-17-(tert-butoxy)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | C23H36O2 | 详情 | 详情 | |
| (IV) | 62425 | 3-[(3S,3aS,6R)-3-(tert-butoxy)-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl]propanoic acid | C22H36O4 | 详情 | 详情 | |
| (V) | 62426 | (4aR,6aS,7S)-7-(tert-butoxy)-4a,6a-dimethyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydroindeno[5,4-f]chromen-2(3H)-one | C22H34O3 | 详情 | 详情 | |
| (VI) | 62427 | (1R,5S,6S)-6-(tert-butoxy)-13-hydroxy-1,5,13-trimethyltetracyclo[10.3.1.0~2,10~.0~5,9~]hexadecan-16-one | C23H38O3 | 详情 | 详情 | |
| (VII) | 62424 | (10R,13S,17S)-17-(tert-butoxy)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | C23H36O2 | 详情 | 详情 | |
| (VIII) | 54210 | 17beta-Hydroxyandrost-4-en-3-one; 4-Androsten-17-beta-ol-3-one; Android; Androlin; delta4-Androsten-17beta-ol-3-one; Halotensin; Oreton; Testex; Testoderm; Testosterone; Testred; Virilon | 58-22-0 | C19H28O2 | 详情 | 详情 |
| (IX) | 62428 | (5S,10S,13S,17S)-17-hydroxy-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | C19H30O2 | 详情 | 详情 | |
| (X) | 62429 | (5S,10S,13S)-10,13-dimethyldodecahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,4H)-dione | C19H28O2 | 详情 | 详情 | |
| (XI) | 62430 | (3S,5S,10S,13S)-3-hydroxy-10,13-dimethylhexadecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H30O2 | 详情 | 详情 |