Development of Highly Versatile C_4-Chiral Building Blocks from L-Malic acid and Their Utilization in Natural Product Syntheses

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This research aims at developing highly versatile C_4-chiral synthons from L-malic acid which should enjoy large popularity in natural product syntheses. A newly developed method for selective reduction of alpha-hydroxy esters has provide a number of otherwise inaccessible chiral synthons which constitutes the central strategy in this research. The selective reduction involves, in principle, hydroxy-directed activation of the alpha-ester group and turned out to be applicable to L-tartrate-based derivatives which provided additional diverse chiral synthons. A various types of synthetic intermediates furnished by this reduction bears commonly one ester group and 3,4-dihydroxy functionality. This structural feature promises potent possibilities in a myriad of contexts for organic transformations which follows therefrom because the 3,4-dihydroxy functionality is amenable to selective easy protection and the ester group can be embodied in target molecule if so desired. We have prepared the following compounds of synthetic and biological interests starting from such chiral synthons : gamma-lactone derivative, cis-and trans-2,3-epoxy esters, (S) -glyceraldehyde acetonide, carnitine and unnatural functional alpha-amino acids, beta-lactam derivatives, heterocyclic compounds, octahydronaphthalene derivatives, and cyclopentane derivatives. When coupled with an idea to introduce formyl functionality by Claisen rearrangement, ene-carbacyclization strategy employed in the synthesis of the cyclopentane derivatives has led to a hopeful stage in which an extremely fascinating synthetic work directed toward isocarbacyclin can become available. The synthetic route developed by us should put stress on the point that it constitutes the most short-cut route to isocarbacyclin among those reported so far.