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【结 构 式】 
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【分子编号】62424 【品名】(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 【CA登记号】 |
【 分 子 式 】C23H36O2 【 分 子 量 】344.53764 【元素组成】C 80.18% H 10.53% O 9.29% |
合成路线1
该中间体在本合成路线中的序号：(VII)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 |
合成路线2
该中间体在本合成路线中的序号：(III)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 |