Facile synthesis of structurally diverse 5-oxopiperazine-2-carboxylates as dipeptide mimics and templates

Org Biomol Chem. 2009 Aug 21;7(16):3338-42. doi: 10.1039/b908548c. Epub 2009 Jun 30.

Abstract

A sequence of Michael addition of a primary amine onto methyl 2-chloro-2-cyclopropylidene-acetate (1), acylation of the adduct with alpha-bromo acid chlorides under modified Schotten-Baumann conditions and ring-closing twofold nucleophilic substitution on the thus formed bishalides 3a-e with aliphatic or aromatic amines according to a very simple protocol with final acid/base extraction or filtration over silica gel for purification leads to the 3-spirocyclopropanated 5-oxopiperazine-2-carboxylates 2 or in two cases, after intermolecular transesterification of 2, to bicyclic oxopiperazines 6, with a remarkable variability of the substituents R1-R3 in 39-99% yields (20 examples). Starting with alpha-bromophenylacetic acid chloride, the trans-configured 6-phenyl-5-oxopiperazine-2-carboxylates are formed preferentially.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Biomimetics / methods
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Dipeptides / chemical synthesis*
  • Molecular Mimicry / physiology*
  • Stereoisomerism

Substances

  • Amines
  • Carboxylic Acids
  • Dipeptides