Studies on Steroids. XLV. Synthesis of the Four Stereoisomers of 20, 22-Dihydroxycholesterol
Studies on Steroids. XLV. Synthesis of the Four Stereoisomers of 20, 22-Dihydroxycholesterol
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类固醇的研究。
DOI：
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发表时间：
1977
期刊：
影响因子：
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通讯作者：
N. Ikekawa
中科院分区：
文献类型：
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作者：
M. Morisaki;Susumu Sato;N. Ikekawa
以异烯醇酮为原料合成了20，22-二羟基胆固醇的4个立体异构体9，10，17和19。3，5-环烯醇酮衍生物1经乙烯基化得到[20 S]-甲醇2，再经间氯过苯甲酸氧化得到[22 S]-22，23-环氧化物3及其[22 R]-异构体4（7：2）。3和4与i-Bu_2CuLi反应，然后酸处理，分别得到20 R，22 S-二羟基胆固醇9及其20 R，22 R-异构体10。后一种三醇10更有效地通过在[20 S]-20-甲酰基-甲醇14上的格氏反应制备，所述[20 S]-20-甲酰基-甲醇14通过1，3-二噻烷衍生物13衍生自双烯醇酮THP醚12。20-脱氢胆固醇乙酸酯16与OsO_4氧化，立体选择性地得到20 S，22 S-乙二醇17（R=Ac）。用N-氯代琥珀酰亚胺-二甲硫醚处理17（R=Ac），然后用LiAlH 4还原，得到20 S，22 R-二羟基胆固醇19和20 S，22 S-异构体17（R=H）（3：2）。对20，22-环氧胆固醇的酸催化环氧开环反应也进行了讨论。
The four stereoisomers of 20, 22-dihydroxycholesterol 9, 10, 17 and 19 were synthesized from pregnenolone. Vinylation of the 3, 5-cyclo derivative 1 of pregnenolone gave the [20S]-carbinol 2, which was then oxidized with m-chloroperbenzoic acid to afford the [22S]-22, 23-epoxide 3 and its [22R]-isomer 4 (7 : 2). Reaction of 3 and 4 with i-Bu2CuLi followed by acid treatment yielded 20R, 22S-dihydroxycholesterol 9 and its 20R, 22R-isomer 10, respectively. The latter triol 10 was more effectively prepared by a Grignard reaction on the [20S]-20-formyl-carbinol 14, which was derived from pregnenolone THP ether 12, through the 1, 3-dithiane derivative 13. Oxidation of 20-dehydrocholesterol acetate 16 with OsO4 gave stereoselectively the 20S, 22S-glycol 17 (R=Ac). Treatment 17 (R=Ac) with N-chlorosuccinimide-dimethylsulfide followed by reduction with LiAlH4 afforded 20S, 22R-dihydroxycholesterol 19 together with the 20S, 22S-isomer 17 (R=H) (3 : 2). Acid-catalyzed epoxide opening reactions of 20, 22-epoxycholesterols were also discussed.