SYNTHESIS OF N-SUBSTITUTED OLIGOMERS

摘要

A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeuti c interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two "sub- monomers" directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amin e bound to the support with an acylating agent comprising a leaving group capable of nucleophilic displacement by -NH2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a solid support-bound a- haloacetamide) with a sufficient amount of a second sub-monomer comprising an -NH2 group, such as a primary amine, alkoxyamine, semicarbazid e, acyl hydrazide, carbazate or the like. Repetition of the two step cycle of acylation and displacement gives the desired oligomers. Combinatorial libraries of cyclic compounds are disclosed wherein the cyclic compounds are comprised of at least one ring structure derived from cyclization of a peptoid backbone. The diversity of product compounds is generated by the sequential addition of substituted sub-monomers. Methods of synthesizing the combinatorial libraries and assay devices produced using the libraries are disclosed as is methodology for screening for and obtaining biologically active cyclic organic compounds.