Libraries of small compact structures based on N-acyl-N-alkylamino acids

The “One-Bead-One-Compound” Combinatorial Library Method

“…The first attempt to depart from the structure of peptides, although still using mostly amide bond chemistry, is documented by the synthesis of a library of 8000 N -alkyl- N -acyl amino acids. , Polymer-supported amino acids were alkylated under the conditions of reductive amination with a variety of aldehydes, resulting in secondary amines which were acylated with carboxylic acids. The library was screened to determine specific binders to a model target, streptavidin, and the structure of positively reacting compounds was determined using mass spectrometry.…”

“…Numerous organic reactions useful for solid-phase combinatorial chemistry have been reported in the literature. These include reductive alkylation; ,,, Mitsunobu etherification − and esterification; carbon−carbon bond-forming reactions such as Horner/Wittig, , Grignard, Heck, , Stille, ,− and Suzuki reactions; ,− Michael addition; and amide reduction. , One should be able to use these reactions in the design of heterogeneous libraries.…”

Molecular Diversity and Libraries of Structures: Synthesis and Screening

“…The same authors have used alkylation and acylation reactions for creation of model libraries 323 as well as for libraries screened for pharmaceutically relevant targets (Scheme 11). Unnatural amino acids, aldehydes and carboxylic acids were used for construction of the library by use of reductive alkylation of the primary amino group by various aldehydes and acylation of the resulting secondary amino groups with diverse carboxylic acids 326,327 . A library was screened against streptavidin and the structure of active compounds was determined by mass spectroscopy 326 .…”