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【结 构 式】 
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【分子编号】33520 【品名】(2R,4aS,6aS,6bS,9aR,10aS,10bS)-6b-acetyl-4a,6a,8-trimethyl-2,3,4,4a,6,6a,6b,9a,10,10a,10b,11,12,12a-tetradecahydro-1H-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-2-yl acetate; 3beta-acetoxy-5alpha-pregn-9(11)-ene-20-one-[17alpha,16alpha-d]-2'-methyloxazoline 【CA登记号】19890-68-7 |
【 分 子 式 】C25H35NO4 【 分 子 量 】413.55724 【元素组成】C 72.61% H 8.53% N 3.39% O 15.47% |
合成路线1
该中间体在本合成路线中的序号：(X)The monoacetylation of (V) with acetic anhydride and pyridine at 100 C gives the 3-acetoxy-11-hydroxy compound (IX), which is dehydrated by treatment with methanesulfonyl chloride and then with sodium acetate yielding 3beta-acetoxy-5alpha-pregn-9(11)-ene-20-one-[17alpha,16alpha-d]-2'-methyloxazoline (X). The hydrolysis of (X) with KOH in refluxing methanol affords the corresponding hydroxy compound (XI), which is acetoxylated by treatment with I2 and AZBN as before giving the iodo derivative (XII), and then with triethylammonium acetate also as before, yielding 3beta-hydroxy-21-acetoxy-5alpha-pregn-9(11)-ene-20-one-[17alpha,16alpha-d]-2'-methyloxazoline (XIII). The oxidation of (XIII) with CrO3 in acetone yields the 3,20-diketone (XIV), which by treatment with Br2 and Li2CO3 as before is dehydrogenated affording the 1,4,9(11)-pregnatriene (XV). Finally, the reaction of (XV) with N-bromoacetamide in THF yields 9alpha-bromo-11beta-hydroxy-21-acetoxy-5alpha-pregna-1,4-dieno-3,20-dione-[17alpha,16alpha-d]-2'-methyloxazoline (XVI), which is then debrominated by reaction with chromous acetate and butanethiol in DMSO.
| 【1】 Nathansohn, G.; et al.; Steroids possessing nitrogen atoms. IV. Further studies on the synthesis of [17-alpha,16alpha-d]ozazolino corticoids. Steroids 1969, 13, 383. |
| 【2】 Castaner, J.; de Angelis, L.; Aclacinomycin A. Drugs Fut 1978, 3, 3, 171. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 33515 | 1-[(2R,4aS,4bS,5S,6aS,9aR,10aS,10bS)-2,5-dihydroxy-4a,6a,8-trimethyl-1,2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12,12a-hexadecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-1-ethanone | 13649-86-0 | C23H35NO4 | 详情 | 详情 |
| (IX) | 33519 | (2R,4aS,4bS,5S,6aS,6bS,9aR,10aS,10bS)-6b-acetyl-5-hydroxy-4a,6a,8-trimethyl-2,3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12,12a-hexadecahydro-1H-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-2-yl acetate | 13649-87-1 | C25H37NO5 | 详情 | 详情 |
| (X) | 33520 | (2R,4aS,6aS,6bS,9aR,10aS,10bS)-6b-acetyl-4a,6a,8-trimethyl-2,3,4,4a,6,6a,6b,9a,10,10a,10b,11,12,12a-tetradecahydro-1H-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-2-yl acetate; 3beta-acetoxy-5alpha-pregn-9(11)-ene-20-one-[17alpha,16alpha-d]-2'-methyloxazoline | 19890-68-7 | C25H35NO4 | 详情 | 详情 |
| (XI) | 33521 | 1-[(2R,4aS,6aS,9aR,10aS,10bS)-2-hydroxy-4a,6a,8-trimethyl-1,2,3,4,4a,6,6a,9a,10,10a,10b,11,12,12a-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-1-ethanone | C23H33NO3 | 详情 | 详情 | |
| (XII) | 33522 | 1-[(2R,4aS,6aS,9aR,10aS,10bS)-2-hydroxy-4a,6a,8-trimethyl-1,2,3,4,4a,6,6a,9a,10,10a,10b,11,12,12a-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-2-iodo-1-ethanone | C23H32INO3 | 详情 | 详情 | |
| (XIII) | 33523 | 2-[(2R,4aS,6aS,9aR,10aS,10bS)-2-hydroxy-4a,6a,8-trimethyl-1,2,3,4,4a,6,6a,9a,10,10a,10b,11,12,12a-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-2-oxoethyl acetate; 3beta-hydroxy-21-acetoxy-5alpha-pregn-9-(11)-ene-20-one-[17alpha,16alpha-d]-2'-methyloxazoline | 19890-70-1 | C25H35NO5 | 详情 | 详情 |
| (XIV) | 33524 | 2-[(4aS,6aS,9aR,10aS,10bS)-4a,6a,8-trimethyl-2-oxo-1,2,3,4,4a,6,6a,9a,10,10a,10b,11,12,12a-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-2-oxoethyl acetate | 19890-71-2 | C25H33NO5 | 详情 | 详情 |
| (XV) | 33525 | 2-[(4aR,6aS,9aR,10aS,10bS)-4a,6a,8-trimethyl-2-oxo-2,4a,6,6a,9a,10,10a,10b,11,12-decahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-2-oxoethyl acetate | 16119-56-5 | C25H29NO5 | 详情 | 详情 |
| (XVI) | 33526 | 2-[(4aS,4bR,5S,6aS,9aR,10aS,10bS)-4b-bromo-5-hydroxy-4a,6a,8-trimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-2-oxoethyl acetate; 9alpha-bromo-11beta-hydroxy-21-acetoxy-5alpha-pregna-1,4-dieno-3,20-dione-[17alpha,16alpha-d]-2'-methyloxazoline | C25H30BrNO6 | 详情 | 详情 |