Solution-Phase Preparation of a 560-Compound Library of Individual Pure Mappicine Analogues by Fluorous Mixture Synthesis

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• 作者：Wei Zhang ; Zhiyong Luo ; Christine Hiu-Tung Chen ; and Dennis P. Curran
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：September 4, 2002
• 年：2002
• 卷：124
• 期：35
• 页码：10443 - 10450
• 全文大小：173K
• 年卷期：v.124,no.35(September 4, 2002)
• ISSN：1520-5126

文摘

Solution-phase mixture synthesis has efficiency advantages and favorable reaction kinetics.Applications of this technique, however, have been discouraged by the difficulty in obtaining individual,pure final products by using conventional separation and identification processes. Introduced here is anew strategy for mixture synthesis that addresses the separation and identification problems. Members ofa series of organic substrates are paired with a series of fluorous tags of different chain lengths. The taggedstarting materials are then mixed and taken through a multistep reaction process. Fluorous chromatographyis used to demix the tagged product mixtures on the basis of the fluorine content of the tags to provide theindividual pure components of the mixture, which are detagged to release the final products. The utility offluorous mixture synthesis is demonstrated by the preparation of a 560-membered library of analogues ofthe natural product mappicine. A seven-component mixture is carried through a four-step mixture synthesis(two one-pot and two parallel steps) to incorporate two additional points of diversity onto the tetracycliccore. Methods for analysis and purification of the intermediates are established for the quality control ofthe mixture synthesis.