Partners and International Organizations
(English)
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A, B, HR, CZ, DK, F, D, GR, H, IRL, I, LV, NL, N, PL, P, SK, SI, E, S, CH, GB
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Abstract
(English)
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This working group is devoted to the developments of new synthetic methods to be applied to the synthesis of bioactive natural products and of analogs. The target molecules are polyketides in general, including polypropionates, complicated molecular fragments found in antibiotics such as enythromycines and cytotoxic agents such as discodermolide, apoptolidine, spongistatines, etc. Our group has invented a new carbon-carbon forming reaction that implies a reaction cascade, i.e.: the hetero-Diels-Alder addition of sulfur dioxide with 1-oxy-1,3-dienes, the alkylation of enoxysilanes by the intermediate sultines, the desulfitation of the silyl sulfinates formed via a retro-ene reaction. Thus mixtures of enoxysilanes and 1-oxy-1,3-dienes are converted into polypropionate fragments containing up to three contiguous stereogenic centers and one (E)-alkene unit. Fundamental studies are required to understand the stereoselectivity of this new reaction and applications to the construction of complicated structures has now been started. Our group has developed another approach to the total synthesis of polypropionates, that of the 'naked sugars of the second generation'. This methodology has been applied to the total asymmetric synthesis of a new 9,12-anhydroerythronolide aglycone. The new organic chemistry of sulfur dioxide developed in Lausanne has permitted the invention of a one-pot three- and a one-pot four-component synthesis of polyfunctional sulfones. This work opens the possibility to generate a large variety of peptidomimetics.Long-chain polyketides with amino groups are rare natural compounds that show interesting biological properties (e.g.: Linearmycin A,B, Zwittermycin A). Starting from 2,2'-methylenedifuran, enantiomerically enriched (98 %) 1-aminopentadecane-3,5,7,9,11,13,15-heptols and 1,15-diamino-pentadecane-3,5,7,9,11,13-hexols and semi-protected derivatives have been prepared for the first time.
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