Lewbart M L, Annan R S, Arison B H, Springer J P, Gould S R
Department of Medicine, Crozer-Chester Medical Center, PA 19013.
J Pharm Sci. 1990 May;79(5):373-8. doi: 10.1002/jps.2600790502.
The reaction of 17 alpha-benzoyloxy-11 beta-hydroxy-3,20-dioxo-1, 4-pregnadien-21-al as the hemiacetal (1) with methanol:acetic acid:potassium cyanide:manganese dioxide followed by acetylation and preparative HPLC of the reaction mixture afforded 11 crystalline products. These products can be conveniently divided into three categories representing side-chain cleavage and oxidative esterification with or without elimination of the benzoyloxy group. Of special interest was the stereospecific formation of the C-17 cyanohydrin acetate 4a and the cis delta 17(20) enol acetate methyl ester 5. On the other hand, nonstereospecific addition of HCN to the side chain gave the C-20 epimeric cyanohydrin acetates 7a and 7b. The use of activated versus nonactivated MnO2 plays a major role in determining the quantitative distribution of the products. It was also discovered that even in the absence of MnO2, the reaction goes to completion. A proposed mechanism which explains the formation of all products is presented.
17α - 苯甲酰氧基 - 11β - 羟基 - 3,20 - 二氧代 - 1,4 - 孕甾二烯 - 21 - 醛作为半缩醛（1）与甲醇：乙酸：氰化钾：二氧化锰反应，随后对反应混合物进行乙酰化和制备型高效液相色谱分析，得到了11种结晶产物。这些产物可方便地分为三类，分别代表有或没有苯甲酰氧基消除的侧链裂解和氧化酯化反应。特别有趣的是C - 17氰醇乙酸酯4a和顺式δ17(20)烯醇乙酸甲酯5的立体特异性形成。另一方面，HCN对侧链的非立体特异性加成得到了C - 20差向异构氰醇乙酸酯7a和7b。使用活性二氧化锰与非活性二氧化锰在决定产物的定量分布方面起着主要作用。还发现即使在没有二氧化锰的情况下，反应也能完成。本文提出了一个解释所有产物形成的机理。
