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【结 构 式】 
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【分子编号】59412 【品名】(8R,9S,13S,14S)-3-(benzyloxy)-2-methoxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one 【CA登记号】 |
【 分 子 式 】C26H30O3 【 分 子 量 】390.5224 【元素组成】C 79.97% H 7.74% O 12.29% |
合成路线1
该中间体在本合成路线中的序号：(IX)In an alternative method, the hydroxyl group of estrone (V) was protected as the benzyl ether (VI), which was subsequently subjected to electrophilic nitration to yield selectively the 2-nitro derivative (VII). After reduction of (VII) to the corresponding amine (VIII), replacement of the amino for a methoxy group was performed by diazotization, followed by treatment with sodium methoxide, using Sandmeyer conditions. Finally hydrogenolysis of the O-benzyl protecting group, with simultaneous ketone reduction led to the desired 2-methoxy estradiol.
| 【1】 Shah, J.H.; Agoston, G.E.; Treston, A.M. (EntreMed, Inc.); Methods of obtaining 2-methoxyestradiol of high purity. WO 0114405 . |
| 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) | 20468 | (8R,9S,13S,14S)-3-hydroxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | 53-16-7 | C18H22O2 | 详情 | 详情 |
| (VI) | 50978 | (8R,9S,13S,14S)-3-(benzyloxy)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C25H28O2 | 详情 | 详情 | |
| (VII) | 59410 | (8R,9S,13S,14S)-3-(benzyloxy)-13-methyl-2-nitro-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C25H27NO4 | 详情 | 详情 | |
| (VIII) | 59411 | (8R,9S,13S,14S)-2-amino-3-(benzyloxy)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C25H29NO2 | 详情 | 详情 | |
| (IX) | 59412 | (8R,9S,13S,14S)-3-(benzyloxy)-2-methoxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C26H30O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The known 17-hydroxy steroid (I) is oxidized to the corresponding ketone (II) by means of the Jones reagent in acetone. After protection of the ketone (II) as the ethylidene ketal (III), removal of the 3-benzyl ether under transfer hydrogenation conditions furnishes the phenol (IV), which is esterified with acetic anhydride in pyridine to give the aryl acetate (V). Bromination at the alpha-position of the ketalized keto group of (V) is carried out in the presence of phenyltrimethylammonium tribromide in cold THF to produce the 16-alpha-bromide (VI). Dehydrobromination of (VI) with simultaneous acetate hydrolysis upon treatment with potassium tert-butoxide leads to the olefin (VII). Subsequent acidic hydrolysis of ketal (VII) gives the enone (VIII), which is further acylated with isopropenyl acetate and acetic anhydride in the presence of p-toluenesulfonic acid to furnish the dienyl acetate (IX). Finally, reductive treatment of (IX) with sodium borohydride affords the target diol.
| 【1】 Rao, P.N.; Cessac, J.W.; Tinley, T.L.; Moberry, S.L.; Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs. Steroids 2002, 67, 13-14, 1079. |
| 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) | 59436 | (8R,9S,13S,14S,17S)-3-(benzyloxy)-2-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol | C26H32O3 | 详情 | 详情 | |
| (II) | 59412 | (8R,9S,13S,14S)-3-(benzyloxy)-2-methoxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C26H30O3 | 详情 | 详情 | |
| (III) | 64856 | C28H34O4 | 详情 | 详情 | ||
| (IV) | 64857 | C21H28O4 | 详情 | 详情 | ||
| (V) | 64858 | C23H30O5 | 详情 | 详情 | ||
| (VI) | 64859 | C23H29BrO5 | 详情 | 详情 | ||
| (VII) | 64860 | C21H26O4 | 详情 | 详情 | ||
| (VIII) | 64861 | (8R,9S,13S,14R)-3-hydroxy-2-methoxy-13-methyl-6,7,8,9,11,12,13,14-octahydro-17H-cyclopenta[a]phenanthren-17-one | C19H22O3 | 详情 | 详情 | |
| (IX) | 64862 | (8R,9S,13S)-17-(acetyloxy)-2-methoxy-13-methyl-7,8,9,11,12,13-hexahydro-6H-cyclopenta[a]phenanthren-3-yl acetate | C23H26O5 | 详情 | 详情 |