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【结 构 式】 
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【分子编号】20083 【品名】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 【CA登记号】853-23-6 |
【 分 子 式 】C21H30O3 【 分 子 量 】330.4674 【元素组成】C 76.33% H 9.15% O 14.52% |
合成路线1
该中间体在本合成路线中的序号：(I)Dehydroepiandrosterone acetate (I) is converted to the lactam (II), which is hydrolyzed to the alcohol (III). Oppenauer oxidation of (III) gives the a,3-unsaturated ketone (IV). The intermediate (IV) is treated with pyrrolidine in methanol to give the enamine (V) in excellent yield. The latter, on sodium borohydride reduction affords (VI), the 3beta- configuration being assigned on the basis of similar reductions reported elsewhere. Sodium and n-pentanol reduction of (VI) leads to the diamine (VII), the methyl derivative (VIII) of which is prepared and converted into the dimethiodide (HS-310).
| 【1】 Singh, H.; Paul, D.; Steroids and related studies. Part XXV. Chandonium iodide (17alpha-Methyl-3beta-pyrrolidino-17alpha-aza-D-homoandrost-5-ene-Dimethyliodide) and other quaternary ammonium steroid analogues. J Chem Soc - Perkins Trans I 1974, 1476. |
| 【2】 Schmitt, J.; et al.; Recherches sur les amino-stéroïdes. VI. Stéroïdes à restes aminés fixés en C3. Préparation par réduction au borohydrurre de sodium et au diborane des "énamines" derivées de céto-3. Bull Soc Chim France 1963, 807-815. |
| 【3】 Marshall, J.A.; Johnson, W.S.; Reduction od steroidal enamines. J Org Chem 1963, 28, 421-423. |
| 【4】 Arya. V.P.; Chandonium iodide. Drugs Fut 1978, 3, 11, 807. |
| 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) | 39912 | (4aS,4bR,8S,10aR,10bS,12aS)-10a,12a-dimethyl-2-oxo-1,2,3,4,4a,4b,5,7,8,9,10,10a,10b,11,12,12a-hexadecahydronaphtho[2,1-f]quinolin-8-yl acetate | C21H31NO3 | 详情 | 详情 | |
| (III) | 39913 | (4aS,4bR,8S,10aR,10bS,12aS)-8-hydroxy-10a,12a-dimethyl-3,4,4a,4b,5,7,8,9,10,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]quinolin-2(1H)-one | C19H29NO2 | 详情 | 详情 | |
| (IV) | 39914 | (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-1,3,4,4a,4b,5,6,9,10,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]quinoline-2,8-dione | C19H27NO2 | 详情 | 详情 | |
| (V) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (VI) | 39915 | (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-8-(1-pyrrolidinyl)-3,4,4a,4b,5,9,10,10a,10b,11,12,12a-dodecahydronaphtho[2,1-f]quinolin-2(1H)-one | C23H34N2O | 详情 | 详情 | |
| (VII) | 39916 | (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-8-(1-pyrrolidinyl)-3,4,4a,4b,5,7,8,9,10,10a,10b,11,12,12a-tetradecahydronaphtho[2,1-f]quinolin-2(1H)-one | C23H36N2O | 详情 | 详情 | |
| (VIII) | 39917 | (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-8-(1-pyrrolidinyl)-1,2,3,4,4a,4b,5,7,8,9,10,10a,10b,11,12,12a-hexadecahydronaphtho[2,1-f]quinoline | C23H38N2 | 详情 | 详情 | |
| (IX) | 39918 | (4aS,4bR,10aR,10bS,12aS)-1,10a,12a-trimethyl-8-(1-pyrrolidinyl)-1,2,3,4,4a,4b,5,7,8,9,10,10a,10b,11,12,12a-hexadecahydronaphtho[2,1-f]quinoline | C24H40N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXVI)In a synthetic route starting from dehydroepiandrosterone (LXVI), Wittig reaction of ketone (LXVI) with ethyl triphenylphosphonium bromide (LXVII) and potassium tert-butoxide gave the C-17 ethylidene derivative (LXVIII). Condensation of (LXVIII) with isopropyl vinyl ketone (LXIX) in the presence of dimethylaluminum chloride, followed by catalytic hydrogenation over Pt/C, yielded (LV), which was then converted into ethylene ketal (LVI). Catalytic hydrogenation of (LVI) gave compound (LXX), whose acetate ester was hydrolyzed to afford alcohol (LXXI). Oxidation of (LXXI) by means of chromic acid furnishes ketone (LXXII), from which intermediate (LX) was obtained by introduction of the 7-alpha hydroxyl group by means of microbiological oxidation employing several microorganism strains.
| 【1】 Moriarty, R.M.; Guo, L.; Tuladhar, S.M. (Genaera Corp.); Chemical synthesis of squalamine. WO 9419366 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LV) | 53712 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethyl-4-oxohexyl]-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 | n/a | C29H46O3 | 详情 | 详情 |
| (LVI) | 53739 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-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 | n/a | C31H50O4 | 详情 | 详情 |
| (LX) | 53754 | (3S,8S,9S,10R,13S,14S,17S)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C25H38O4 | 详情 | 详情 |
| (LXVI) | 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 |
| (LXVII) | 11717 | Ethyl(triphenyl)phosphonium bromide; (Ethyl)triphenylphosphonium bromide | 1530-32-1 | C20H20BrP | 详情 | 详情 |
| (LXVIII) | 53749 | (3S,8S,9S,10R,13S,14S)-17-[(E)ethylidene]-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 | n/a | C23H34O2 | 详情 | 详情 |
| (LXIX) | 53750 | 4-methyl-1-penten-3-one | 1606-47-9 | C6H10O | 详情 | 详情 |
| (LXX) | 53751 | (3S,5S,8R,9S,10S,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | n/a | C31H52O4 | 详情 | 详情 |
| (LXXI) | 53752 | (3S,5S,8R,9S,10S,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol | n/a | C29H50O3 | 详情 | 详情 |
| (LXXII) | 53753 | (5S,8R,9S,10S,13R,14S,17R)-17-[(1R)-3-(2-isopropyl-1,3-dioxolan-2-yl)-1-methylpropyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C29H48O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Treatment of dehydroepiandrosterone 3-acetate (I) with triflic anhydride and 2,6-di-tert-butyl-4-methylpyridine provided the desired enol triflate (III) along with some 3,5-diene (II), which were separated by column chromatography. Subsequent coupling of triflate (III) with pyridylborane (IV) using bis(triphenylphosphine)- palladium(II) chloride as the catalyst afforded the (3-pyridyl)androstadiene (V), which after hydrolysis of the acetate ester with NaOH provided the target compound.
| 【1】 Potter, G.A.; et al.; Novel steroidal inhibitors of human cytochrome P450(17alpha) (17alpha-hydroxylase-C17,20-lyase): Potential agents for the treatment of prostatic cancer. J Med Chem 1995, 38, 13, 2463. |
| 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) | 20084 | (8R,9S,10R,13S,14S)-10,13-dimethyl-2,7,8,9,10,11,12,13,14,15-decahydro-1H-cyclopenta[a]phenanthren-17-yl trifluoromethanesulfonate | C20H25F3O3S | 详情 | 详情 | |
| (III) | 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 | |
| (IV) | 20086 | 3-(diethylboryl)pyridine | C9H14BN | 详情 | 详情 | |
| (V) | 20087 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(3-pyridinyl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C26H33NO2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)The Vilsmeier-Haack reaction of 3-beta-acetoxyandrost-5-en-17-one (I) using POCl3 and DMF produced a mixture of the vinyl chloride (II) and its formyl derivative (III). After chromatographic separation, the chlorine atom of (III) was displaced with 1,2,3-triazole (IV) to afford the desired 1-triazolyl compound (V) along with the 2-triazolyl regioisomer (VI), which were separated by flash chromatography. Cleavage of the formyl group from compound (V) was carried out by treatment with bis(triphenylphosphine)rhodium(I)carbonyl chloride and 1,3-bis(diphenylphosphino)propane in hot xylenes to furnish (VII). The acetate ester group was finally hydrolyzed with methanolic KOH.
| 【1】 Njar, V.C.O.; Grigoryev, D.N.; Long, B.J.; Kato, K.; Brodie, A.M.H.; Nnane, I.P.; Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17alpha-hydroxylase-C17,20-lyase (P45017alpha): Potential agents for the treatment of prostate cancer. J Med Chem 1998, 41, 6, 902. |
| 【2】 Brodie, A.; Njar, V.C.O. (University of Maryland); 17-Azolyl steroids useful as androgen synthesis inhibitors. US 5994335 . |
| 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) | 42853 | (3S,8R,9S,10R,13S,14S)-17-chloro-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C21H29ClO2 | 详情 | 详情 | |
| (III) | 42854 | (3S,8R,9S,10R,13S,14S)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H29ClO3 | 详情 | 详情 | |
| (IV) | 29404 | 1H-1,2,3-triazole | 288-36-8 | C2H3N3 | 详情 | 详情 |
| (V) | 42856 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(2H-1,2,3-triazol-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VI) | 42855 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VII) | 42857 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C23H31N3O2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(I)The Vilsmeier-Haack formylation of 3-beta-acetoxyandrost-5-en-17-one (I) with POCl3/DMF provides the desired chloro aldehyde (III) along with minor amounts of the vinyl chloride (II), which are separated by column chromatography. Condensation of (III) with imidazole (IV) by means of K2CO3 in hot DMF yields derivative (V), which by decarbonylation of its 16-formyl group employing a modified Wilkinson’s catalyst gives (VI). The hydrolysis of the acetate group of (VI) with KOH in methanol affords the corresponding alcohol (VII), which is finally oxidized with aluminum isopropoxide and 1-methyl-4-piperidone in refluxing xylene.
| 【1】 Njar, V.C.O.; Grigoryev, D.N.; Long, B.J.; Kato, K.; Brodie, A.M.H.; Nnane, I.P.; Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17alpha-hydroxylase-C17,20-lyase (P45017alpha): Potential agents for the treatment of prostate cancer. J Med Chem 1998, 41, 6, 902. |
| 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) | 42853 | (3S,8R,9S,10R,13S,14S)-17-chloro-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C21H29ClO2 | 详情 | 详情 | |
| (III) | 42854 | (3S,8R,9S,10R,13S,14S)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H29ClO3 | 详情 | 详情 | |
| (IV) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (V) | 42859 | (3S,8R,9S,10R,13S,14S)-16-formyl-17-(1H-imidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C25H32N2O3 | 详情 | 详情 | |
| (VI) | 42860 | (3S,8R,9S,10R,13S,14S)-17-(1H-imidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H32N2O2 | 详情 | 详情 | |
| (VII) | 42861 | (3S,8R,9S,10R,13S,14S)-17-(1H-imidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol | C22H30N2O | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(I)The Vilsmeier-Haack formylation of 3-beta-acetoxyandrost-5-en-17-one (I) with POCl3/DMF provides the desired chloro aldehyde (III) along with minor amounts of the vinyl chloride (II), which are separated by column chromatography. Condensation of (III) with 1,2,3-triazole (IV) affords two regioisomeric triazole derivatives, (V) and (VI). After chromatographic isolation of the required 1-triazolyl compound (VI), decarbonylation of the 16-formyl group employing a modified Wilkinson’s catalyst gives (VII). The hydrolysis of the acetate group of (VII) with KOH in methanol gives the corresponding alcohol (VIII) , which is finally oxidized with aluminum isopropoxide and 1-methyl-4-piperidone in refluxing xylene.
| 【1】 Njar, V.C.O.; Grigoryev, D.N.; Long, B.J.; Kato, K.; Brodie, A.M.H.; Nnane, I.P.; Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17alpha-hydroxylase-C17,20-lyase (P45017alpha): Potential agents for the treatment of prostate cancer. J Med Chem 1998, 41, 6, 902. |
| 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) | 42853 | (3S,8R,9S,10R,13S,14S)-17-chloro-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C21H29ClO2 | 详情 | 详情 | |
| (III) | 42854 | (3S,8R,9S,10R,13S,14S)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H29ClO3 | 详情 | 详情 | |
| (IV) | 29404 | 1H-1,2,3-triazole | 288-36-8 | C2H3N3 | 详情 | 详情 |
| (V) | 42856 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(2H-1,2,3-triazol-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VI) | 42855 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VII) | 42857 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C23H31N3O2 | 详情 | 详情 | |
| (VIII) | 42858 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol | C21H29N3O | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(I)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 |
合成路线8
该中间体在本合成路线中的序号：(Ia)Abiraterone acetate has been synthesized by two related routes.
a) Reaction of dehydroepiandrosterone acetate (Ia) with trifluoromethanesulfonic anhydride and triethylamine in dichloromethane gives the enol triflate (II), which is finally coupled with diethyl(3-pyridyl)borane (III) by means of PdCl2(PPh3)4 in tetrahydrofuran .
b) In an improved procedure, dehydroepiandrosterone (Ib) is converted to the corresponding hydrazone (IV) by treatment with hydrazine hydrate and a catalytic amount of hydrazine sulfate in EtOH. Subsequent reaction of hydrazone (IV) with iodine and 1,1,3,3-tetramethylguanidine (TMG) in THF/Et2O gives the vinyl iodide (V), which undergoes palladium–catalyzed cross coupling with diethyl(3-pyridyl)borane (III) to yield abiraterone (VI). Finally, alcohol (VI) is acetylated using acetic anhydride in pyridine .
| 【1】 Potter, G.A., Barrie, S.E., Jarman, M., Rowlands, M.G. Novel steroidal inhibitors of human cytochrome P45017α (17α-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer. J Med Chem 1995, 38(13): 2463-71. |
| 【2】 Barrie, S.E., Jarman, M., Potter, G.A. (BTG plc.). 17-Substituted steroids useful in cancer treatment. EP 0633893, GB 2265624, US 5604213, WO 1993020097. |
| 【3】 Hunt, N.J. (BTG International Ltd). Methanesulfonate salts of abiraterone-3-esters and recovery of salts of abiraterone-3-esters from solution in methyl tert-butyl ether. CA 2576922, EP 1789432, JP 2008510780, US 2007249837, WO 2006021776. |
| 【4】 Bury, P.S. (BTG International Ltd.). Process for the preparation of 17-Ovinyl-triflates as intermediates. EP 1781683, JP 2008510781, US 2007282109, WO 2006021777. |
| 【5】 Potter, G.A. and Hardcastle, I.R. (BTG International Ltd). Synthesis of 17-(3-pyridyl) steroids. CA 2170286, EP 0721461, GB 2282377, JP 1997502994, WO 1995009178. |
| 【6】 Potter, G.A., Hardcastle, I.R., Jarman, M. A convenient, large-scale synthesis of abiraterone acetate [3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene], a potential new drug for the treatment of prostate cancer. Org Prep Proced Int 1997, 29: 123. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Ia) | 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 |
| (Ib) | 11713 | Dehydroepiandrosterone;prasterone；(3S,8R,9S,10R,13S,14S)-3-Hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | 53-43-0 | C19H28O2 | 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) | 20086 | 3-(diethylboryl)pyridine | C9H14BN | 详情 | 详情 | |
| (IV) | 69461 | (3S,8S,9R,10S,13R,E)-17-hydrazono-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol | C19H30N2O | 详情 | 详情 | |
| (V) | 69460 | (3R,8S,9R,10S,13R)-17-iodo-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol | 32138-69-5 | C19H27IO | 详情 | 详情 |
| (VI) | 69462 | (3R,8S,9R,10S,13R)-10,13-dimethyl-17-(pyridin-3-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol | C24H31NO | 详情 | 详情 |