Synthesis of Hexa- and Pentasubstituted Diketopiperazines from Sterically Hindered Amino Acids

2010/03/10 by Zachary Z. Brown, Christian E. Schafmeister · 6 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Chemical Synthesis and Analysis #Carbohydrate Chemistry and Synthesis #Microbial Natural Products and Biosynthesis

paper · doi:10.1021/ol100048g

openalex publication_date 2010/03/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22

Abstract

Steric hindrance assists in the formation of hindered diketopiperazines using acyl-transfer coupling. In acyl-transfer coupling, the carboxylate of an unprotected N-alkylamino acid attacks an active ester to form a transient anhydride that undergoes an O,N acyl transfer to form a tertiary amide. If the active ester is part of an N-alkylamino acid it will form a diketopiperazine. It is demonstrated here that acyl-transfer coupling can assemble highly functionalized bis-peptides bearing a functional group on every monomer.

Citations

• Shape-Programmable Macromolecules
• A Field Guide to Foldamers
• Diketopiperazines: biological activity and synthesis

Cited by

• Acceleration of an Aromatic Claisen Rearrangement via a Designed Spiroligozyme Catalyst that Mimics the Ketosteroid Isomerase Catalytic Dyad
• A Spiroligomer α-Helix Mimic That Binds HDM2, Penetrates Human Cells and Stabilizes HDM2 in Cell Culture
• Architectural Spiroligomers Designed for Binuclear Metal Complex Templating
• Spiroligozymes for Transesterifications: Design and Relationship of Structure to Activity
• Solid‐phase synthesis of functionalized bis‐peptides
• Spiroligomer [wikipedia]