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Abstract

Polypropionates are common products of metabolism in bacteria, insects, fungi and marine organisms. They constitute an important class of products with a wide range of interesting biological activities. Our group has shown previously that 1-alkoxy-3-acyloxy-2-methyl-1,3-pentadienes can undergo hetero-Diels-Alder reactions with SO2, to give the corresponding sultines, which at low temperature in the presence of Lewis acids, can be opened to zwitterionic intermediates. The latter can be trapped by nucleophiles like enoxysilanes (oxyallylation) to generate the corresponding substituted silyl alkenylsulfinate. Desilylation of the latter under acidic conditions leads to intermediate allylsulfinic acids, which, after retro-ene desulfitation, provide a dipropionate stereotriad which is a useful fragment for polypropionate synthesis. Indeed this fragment obtained using this new SO2 reaction cascade, hetero-Diels-Alder addition/oxyallylation/retro-ene desulfitation (Vogel's cascade) is containing keto and enol ester fonctionality which allows the design of the asymmetric total synthesis of complicated polyketides fragments. Firstly a study was made in order to improve the way of synthesis of dienes and their use in Vogel's cascade to improve the diastereoselectivity of the oxyallylation step. The use of this methodology, using (E)-enoxysilanes as nucleophile for the oxyallylation step allowed us to obtain anti,anti-dipropionate stereotriad in high diastereoselectivity. This common subunit found in polyketide-derived natural products has generally been recognized to be difficult to synthesize. This fragment and its properties was used successfully in the first asymmetric total synthesis of the marine natural product dolabriferol. The use of Vogel's cascade with (Z)-enoxysilanes as nucleophile for the oxyallylation step is providing anti-syn-dipropionate stereotriad as major compound. Combination of this method and aldol chemistry allowed us the synthesis of polypropionate fragments in a short sequence. Efforts toward the synthesis of 6-deoxyrythronolide B, and analogues was presented. This strategy allowed us also, to synthesize, in a very efficient way, a lot of compound like lactones which are natural precursor of polypropionate with interesting biological activity or sulfonamide which are well known class of drugs.

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