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【结 构 式】 
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【药物名称】 【化学名称】(3beta,17Z)-3-Hydroxypregna-5,17(20)-dien-21-al oxime 【CA登记号】 【 分 子 式 】C21H31NO2 【 分 子 量 】329.48672 |
【开发单位】Universität des Saarlandes (Originator) 【药理作用】Oncolytic Drugs, Prostate Cancer Therapy, 17alpha-Hydroxylase/C17-20 Lyase Inhibitors |
合成路线1
3-beta-Acetoxyandrost-5-en-17-one (I) was converted into enol triflate (II) by reaction with trifluoromethanesulfonic anhydride in the presence of a hindered base. The subsequent palladium-catalyzed coupling of (II) with ethyl vinyl ether produced a mixture of regioisomeric enol ethers which, after acid hydrolysis, afforded aldehyde (III) and ketone (IV). The minor aldehyde compound (III) was isolated by liquid chromatography and then converted into oxime (V) using hydroxylamine hydrochloride and NaOAc. Finally, the acetate ester group of (V) was hydrolyzed by means of methanolic KOH.
| 【1】 Hartmann, R.W.; Ehmer, P.B.; Hector, M.; Reichert, W.; Jose, J.; Haidar, S.; Synthesis and evaluation of novel steroidal oxime inhibitors of P450 17 (17alpha-hydroxylase/C17-20-lyase)and 5alpha-reductase types 1 and 2. J Med Chem 2000, 43, 22, 4266. |
| 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) | 20083 | Prasterone acetate;3b-Hydroxy-5-androstene-17-one acetate；Dehydroisoandrosterone acetate;Dehydroepiandrosterone 3-acetate;Dehydroepiandrosterone acetate;(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 853-23-6 | C21H30O3 | 详情 | 详情 |
| (II) | 20085 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-[[(trifluoromethyl)sulfonyl]oxy]-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H29F3O5S | 详情 | 详情 | |
| (III) | 45516 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-[(Z)-2-oxoethylidene]-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl acetate | C23H32O3 | 详情 | 详情 | |
| (IV) | 32586 | (3S,8R,9S,10R,13S,14S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 979-02-2 | C23H32O3 | 详情 | 详情 |
| (V) | 45517 | (3S,8R,9S,10R,13S,14S)-17-[(Z)-2-(hydroxyimino)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl acetate | C23H33NO3 | 详情 | 详情 |