Catalytic Asymmetric Syntheses of 2,5‐Diketopiperazine (DKP) Frameworks

Abstract

This mini‐review summarizes catalytic asymmetric synthetic methodologies for preparing 2,5‐diketopiperazine (DKP) frameworks since 1990, with two types of synthetic precursor, namely linear materials and cyclic pre‐chiral substrates, discussed. This review provides guidance for the further design and development of novel catalytic asymmetric methods for preparing functionalized DKP‐containing molecules.

Diastereoselective Spirocyclization: Entry to Spirocyclic Diketopiperazines

“…DKPs are cyclic dipeptide moieties featuring a well-defined geometry and resemblance to protein secondary structures and exhibiting diverse biological and pharmacological activities. − Substituents can be introduced on this motif at the two stereocenters as well as on the amide nitrogen atoms. , When DKPs are fused with another cyclic structure, a spirocyclic framework can be formed that could be utilized as a novel chemotype in drug discovery . The conventional approach to accessing 2,5-diketopiperazine involves sequential amide bond formations to forge the two amino acids and form the cyclic dipeptides. ,,− Alternatively, diastereoselective and catalytic asymmetric methodologies have provided robust approaches to access chiral diketopiperazines from achiral substrates. − Our approach to access 2,5-diketopiperazine-containing spirocyclic compounds proceeds through an orthogonal disconnection strategy (Scheme b).…”

Enantioselective Access to Chiral 2,5-Diketopiperazines via Stereogenic-at-Cobalt(III)-Catalyzed Ugi-4CRs/Cyclization Sequences

“…Besides, the diversity of 2,5-DKP scaffolds was limited by the amounts of available chiral amino acids. During the past decades, several catalytic approaches toward chiral 2,5-DKPs have been developed . One of the facile strategies is asymmetric cyclization from a linear precursor .…”