为了提高海兔毒素(Aplysiatoxin)的产量,合成海兔毒素C9-C21合成子.以1-羟基-2-(S)-甲基丙酸甲酯1为原料,通过醚化和酯还原制得中间体2,同时又以噁唑烷酮3与丙酰氯反应制得中间体4.中间体2和4经羟醛缩合高立体选择性的制备化合物5;接着用TES保护3'-位羟基和脱除噁唑酮并还原得到醇,进一步将羟基碘取代得到化合物8;碘代物8与化合物9反应并进一步水解得到酮10,最后通过Corey不对称还原法(CBS还原)将酮立体选择性的还原为S-羟基化合物11.产品的纯度可达到93%,总收率为29.1%,产物结构均由旋光、NMR和LC-MS确证.%(S)-methyl 3-hydroxy-2-methylpropanoate1was O-protected with the p-methoxybenzylgroupand reduced to the aldehyde2.oxazolidinone wasN-protected with propionyl chloride to obtain compound 4,which was allowed to react with the aldehyde 2 to yield the aldol 5.Protection of the 11-hydroxy l group of compound 5 with thetriethylsily l (TES) groupand subsequent reductiveremoval of the oxazolidinoneyielded the alcohol 7,which was converted to the iodide 8 by halogenation of the hydroxyl group.the iodide 8was reacted with the lithioenamine 9 to yield the ketone 10.Finally,Corey′sasymmetric oxazaborolidine-catalyzed reductionof the 15-keto group of 10 produced the alcohol 11 as s-epimer,which was demonstrated by optical,NMR and LC-MS,in a total yield of 29.1%.The purity of the alcohol 11 could reach up to 93%.
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