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【结 构 式】 
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【分子编号】53783 【品名】(8S,9S,10R,13S,14S,17R)-17-[(1S)-2-hydroxy-1-methylethyl]-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】n/a |
【 分 子 式 】C22H34O2 【 分 子 量 】330.51076 【元素组成】C 79.95% H 10.37% O 9.68% |
合成路线1
该中间体在本合成路线中的序号：(CV)In a further synthetic procedure, ketalization of enone (CV) with ethyleneglycol afforded (CVI). After silylation of the primary alcohol group of (CVI) to (CVII), allylic oxidation by means of tert-butyl hydroperoxide and Cr(CO)6 furnished ketone (CVIII). Catalytic hydrogenation of the double bond of (CVIII) to (CIX), followed by ketone reduction with K-Selectride, gave the C-7 alcohol (CX), which was esterified with benzoyl chloride, yielding benzoate ester (CXI). Subsequent desilylation of (CXI) using tetrabutylammonium fluoride provided (CXII).
| 【1】 Kinney, W.A.; Meckler, H.; Zhang, X.; Lee, N.; Jones, S.; Rao, M.N.; Bulliard, M. (Genaera Corp.); Stereoselective synthesis of 24-hydroxylated cpds. useful for the preparation of aminosterols, vitamin D analogs, and other cpds.. WO 9824800 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (CV) | 53783 | (8S,9S,10R,13S,14S,17R)-17-[(1S)-2-hydroxy-1-methylethyl]-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C22H34O2 | 详情 | 详情 |
| (CVI) | 53784 | n/a | C24H38O3 | 详情 | 详情 | |
| (CVII) | 53785 | n/a | C30H52O3Si | 详情 | 详情 | |
| (CVIII) | 53786 | n/a | C30H50O4Si | 详情 | 详情 | |
| (CIX) | 53787 | n/a | C30H52O4Si | 详情 | 详情 | |
| (CX) | 53788 | n/a | C30H54O4Si | 详情 | 详情 | |
| (CXI) | 53789 | n/a | C37H58O5Si | 详情 | 详情 | |
| (CXII) | 53790 | n/a | C31H44O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(CV)Steroid (CV) was treated with the fungal species Diplodia gossipina to yield the 7-hydroxylated compound (CXXXII) as a fermentation metabolite. Reduction of enone (CXXXII) by lithium in liquid ammonia afforded the saturated ketone (CXXXIII), which was subsequently protected as the ethylene ketal (CXXXIV) by treatment with ethylene glycol and chlorotrimethylsilane. Selective oxidation of the C-22 alcohol group of (CXXXIV) with NaOCl in the presence of TEMPO provided aldehyde (CXXXV). Wadsworth-Emmons condensation of (CXXXV) with phosphonate (CXV) gave enone (CXXXVI). Stereoselective reduction of (CXXXVI) to the 24-(S)-alcohol (CXXXVII) was achieved by treatment with borane-tetrahydrofuran complex in the presence of the chiral catalyst (R)-MeCBS. After catalytic hydrogenation of the double bond of (CXXXVII), the resultant ketal (CXXXVIII) was hydrolyzed to ketone (CXXXIX) under acidic conditions. Sulfation of (CXXXIX) by means of sulfur trioxide-pyridine furnished the key precursor (CXXI), which was then reductively aminated as in the precedent Scheme
| 【1】 Kinney, W.A.; et al.; A short formal synthesis of squalamine from a microbial metabolite. Org Lett 2000, 2, 19, 2921. |
| 【2】 Kinney, W.A.; Zhang, X.; Michalak, R. (Genaera Corp.); A process for the preparation of 7alpha-hydroxy 3-aminosubstd. sterols using intermediates with an unprotected 7alpha-hydroxy group. WO 0179255 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (CV) | 53783 | (8S,9S,10R,13S,14S,17R)-17-[(1S)-2-hydroxy-1-methylethyl]-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C22H34O2 | 详情 | 详情 |
| (CXV) | 53793 | diethyl 3-methyl-2-oxobutylphosphonate | n/a | C9H19O4P | 详情 | 详情 |
| (CXXI) | 53799 | (1R,4R)-4-[(5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-isopropylpentyl hydrogen sulfate | n/a | C27H46O6S | 详情 | 详情 |
| (CXXXII) | 53808 | (7R,8S,9S,10R,13R,14S,17R)-7-hydroxy-17-[(1S)-2-hydroxy-1-methylethyl]-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C22H34O3 | 详情 | 详情 |
| (CXXXIII) | 53809 | (5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-17-[(1S)-2-hydroxy-1-methylethyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C22H36O3 | 详情 | 详情 |
| (CXXXIV) | 53810 | n/a | C24H40O4 | 详情 | 详情 | |
| (CXXXV) | 53811 | n/a | C24H38O4 | 详情 | 详情 | |
| (CXXXVI) | 53812 | n/a | C29H46O4 | 详情 | 详情 | |
| (CXXXVII) | 53813 | n/a | C29H48O4 | 详情 | 详情 | |
| (CXXXVIII) | 53814 | n/a | C29H50O4 | 详情 | 详情 | |
| (CXXXIX) | 53815 | (5S,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C27H46O3 | 详情 | 详情 |