Enzymatic dynamic asymmetric transformation: An efficient entry to enantiopure piperidines

ORGN 768

Roland Udo Braun, braun@organ.su.se1, Karin Leijondahl, karin@organ.su.se2, and Jan-Erling Bäckvall, jeb@organ.su.se1. (1) Department of Organic Chmistry, Universitiy of Stockholm, Arrhenius Laboratoriet, Stockholm, 106 91, Sweden, (2) Department of Organic Chemistry, University of Stockholm, Arrhenius Laboratoriet, Stockholm, 106 91, Sweden
Piperidines constitute an important class of heterocycles and have found broad application for pharmaceutical purposes. As enantiopure compounds are particularly interesting for drug design we set out to elaborate a stereoselective method for the preparation of 2,6-disubstituted piperidines which are substructures in several natural products. Our approach to this class of heterocycles involved a straightforward racemic and non-diastereoselective synthesis of 1,5-diols which were subjected to an enzymatic dynamic kinetic asymmetric transformation (see scheme). In this reaction an enzyme transforms alcohols stereoselectively into the corresponding esters. A ruthenium catalyst racemizes the residual alcohols to yield enantiopure compounds. After hydrolysis of these esters the enantiopure alcohols shall be transformed into mesylates. Piperidines are then formed upon nucleophilic substitution with amines.

 

Asymmetric Reactions, Molecular Recognition, Self Assembly, Bioorganic Chemistry, Process R&D
8:00 PM-10:00 PM, Wednesday, 16 March 2005 Convention Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 14 March 2005 Convention Center -- Sails Pavilion, Sci-Mix

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005