Combinatorial Oligocarbamate Collections: Synthesis by the Premix Method and Quality Control by HPLC‐MS

Abstract

The automated solid phase synthesis of 256 complex oligocarbamate collections by the premix method is described. The collections contain up to 1.9 Â 10 6 compounds built up via synthons derived from 18 proteinogenic amino acids. The quality of the collections is investigated by comparing HPLC and electrospray ionization MS data of the products of the premix synthesis to those of a mixture of individually synthesized single compounds. The premix synthesis was found to yield compound mixtures in qualities sufficient for primary screening assays. For highly complex collections, where the determination of each single compound becomes impossible, the signal patterns of electrospray ionization mass spectrometry were compared to simulated mass distributions and good correlations between theoretical and measured data were observed. Therefore, highly diverse and complex oligocarbamate subcollections and individual compounds are conveniently accessible by optimized and reproducible protocols. The compounds are of particular value for lead finding due to their protease resistance and higher lipophilicity compared to peptides.