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【结 构 式】 
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【分子编号】59851 【品名】(1S,2R,5R,6R,10R,11R,12R,13R,15S)-11,13-dihydroxy-5-[(1R)-5-hydroxy-1,5-dimethylhexyl]-12-(3-hydroxypropoxy)-6,10-dimethyl-18-phenyl-16,18,20-triazahexacyclo[13.5.2.0~1,9~.0~2,6~.0~10,15~.0~16,20~]docos-21-ene-17,19-dione 【CA登记号】 |
【 分 子 式 】C38H55N3O7 【 分 子 量 】665.87072 【元素组成】C 68.54% H 8.33% N 6.31% O 16.82% |
合成路线1
该中间体在本合成路线中的序号：(III)The synthesis of the title compound has been reported starting from the known Diels-Alder adduct (I) of a cholestadiene derivative with 4-phenyl-1,2,4-triazolidinedione. Epoxide ring opening in (I) with 1,3-propanediol (II) in the presence of p-toluenesulfonic acid gave the 1,3-dihydroxy-2-(hydroxypropoxy) derivative (III). Subsequent retro-Diels-Alder reaction in (III) under reductive conditions furnished the cholestadiene compound (IV) (1). In a related sequence, initial retro-cycloaddition reaction in hot dimethylimidazolidinone, followed by ring opening of the resultant epoxide (V) with diol (II) provided an alternative access to diene (IV) (2). Conversion of diene (IV) to the title vitamin D3 analogue was effected by irradiation using a high pressure mercury lamp, followed by thermal isomerization in boiling THF
| 【1】 Miyamoto, K.; Kubodera, N.; Ochi, K.; Matsunaga, I.; Murayama, E. (Chugai Pharmaceutical Co. Ltd.); Vitamin D3 derivs. having a substituent at 2-position. EP 0184206; JP 1986267549; US 4666634 . |
| 【2】 Miyamoto, K.; et al.; Synthetic studies of vitamin D analogues. XIV. Synthesis and calcium regulating activity of vitamin D3 analogues bearing a hydroxyalkoxy group at the 2beta-position. Chem Pharm Bull 1993, 41, 6, 1111. |
| 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) | 59850 | (1S,2R,5R,6R,10R,11S,13S,14R,16S)-14-hydroxy-5-[(1R)-5-hydroxy-1,5-dimethylhexyl]-6,10-dimethyl-19-phenyl-12-oxa-17,19,21-triazaheptacyclo[14.5.2.0~1,9~.0~2,6~.0~10,16~.0~11,13~.0~17,21~]tricos-22-ene-18,20-dione | C35H47N3O5 | 详情 | 详情 | |
| (II) | 14685 | 1,3-propanediol; Trimethylene Glycol | 504-63-2 | C3H8O2 | 详情 | 详情 |
| (III) | 59851 | (1S,2R,5R,6R,10R,11R,12R,13R,15S)-11,13-dihydroxy-5-[(1R)-5-hydroxy-1,5-dimethylhexyl]-12-(3-hydroxypropoxy)-6,10-dimethyl-18-phenyl-16,18,20-triazahexacyclo[13.5.2.0~1,9~.0~2,6~.0~10,15~.0~16,20~]docos-21-ene-17,19-dione | C38H55N3O7 | 详情 | 详情 | |
| (IV) | 59852 | (1R,2R,3R,10R,13R,14R,17R)-17-[(1R)-5-hydroxy-1,5-dimethylhexyl]-2-(3-hydroxypropoxy)-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol | C30H50O5 | 详情 | 详情 | |
| (V) | 59853 | (2R,2aS,3aS,3bR,5aR,6R,8aR)-6-[(1R)-5-hydroxy-1,5-dimethylhexyl]-3b,5a-dimethyl-2,2a,3a,3b,3c,4,5,5a,6,7,8,8a-dodecahydro-1H-cyclopenta[7,8]phenanthro[3,4-b]oxiren-2-ol | C27H42O3 | 详情 | 详情 |