Diastereoselective Multicomponent Reactions of Chemoenzymatically Obtained Chiral Building Blocks

Isocyanide-based multicomponent reactions are a very useful tool for the rapid assembly of libraries of drug-like substances, with the introduction of 3-4 diversity inputs. However, a main drawback of them lies in the poor stereochemical control, which stems form: a) scarce availability of enantiomerically pure chiral components; b) low diastereoselectivity typically obtained. In order to overcome these problems, and at the same time develope a "bioeconomical" approach to a variety of heterocyclic potential drug candidates, we are exploring a general approach involving: a) use of achiral starting materials derived from renewable sources; b) their transformation, through enzymatic processes, into chiral polyfunctionalised building blocks; c) the use of the latter in multicomponent reactions, focussing on optimisation of diastereoselectivity; d) further cyclization steps to access a variety of heterocyclic structures. The first preliminary successful results, employing meso-erythritol as starting material and a diastereoselective Passerini reaction will be presented in this poster.