Amino acid-derived heterocycles as combinatorial library targets: bicyclic aminal lactones.
The incorporation of alpha-amino acids into heterocyclic structures is an effective strategy for generating peptidomimetics and combinatorial library scaffolds. This report describes the synthesis of novel bicyclic aminal 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.
Lewis
Jason G
JG
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Bartlett
Paul A
PA
D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000596:Amino Acids; D007783:Lactones