SOLUTION-PHASE COMBINATORIAL SYNTHESIS - CONVERGENT MULTIPLICATION OFDIVERSITY VIA THE OLEFIN METATHESIS REACTION

The solution-phase synthesis of iminodiacetic acid diamides functional ized with omega-alkenes and their dimerization via the olefin metathes is reaction in the preparation of mixture libraries are detailed. Libr aries containing as many as 113,232 compounds prepared from only N-BOC -iminodiacetic acid anhydride (1), 15 amines, and 4 omega-alkene carbo xylic acids illustrate the diversity that may be achieved by a converg ent versus divergent combination of a small number of monomer building blocks that provides the multiplication of diversity typically associ ated with linear library syntheses including peptides, oligonucleotide s and sequential template functionalizations. Unlike the divergent syn thesis of such libraries which is amenable to solid-phase synthesis te chniques, the convergent synthesis is especially well suited for solut ion-phase synthesis and is precluded by solid-phase techniques since t he combining components typically would be on mutually exclusive phase s. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.