Amino Acid-Derived Heterocycles as Combinatorial Library Targets: Bicyclic Aminal Lactones

摘要

The incorporation of α-amino acids into heterocyclic structures is an effective strategy for generating peptidomimetics and combinatorial scaffolds. This report describes the synthesis of novel bicyclic animal lactones 3 by base-catalyzed cyclization of N-(2-oxoalkyl)-dipeptide esters 8. Assembly of the acyclic precursor 8 can be carried out on solid phase, with variation at four positions; cyclative release ensures high product purity in the final step. Cyclization affords the exo isomer stereospecifically when one chiral center is present in the precursor, or when both amino acids have the same configuration.