Synthesis of cyclic RGD derivatives via solid phase macrocyclization using the Heck reaction

Kenichi Akaji, Kenta Teruya, Masako Akaji, Saburou Aimoto

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

A novel intramolecular macrocyclization reaction on a solid support using the Heck reaction has been achieved. For head to tail cyclization on a solid support, the linear precursor was anchored to a chlorotrityl chloride resin via an ester linkage using the β-carboxyl group of Asp. The Heck coupling of acrylic acid amide to 3-iodobenzylamine on the solid support proceeds smoothly to yield a cyclic tetrapeptide derivative, which contains a new 3-substituted cinnamic acid template and Arg-Gly-Asp sequence. The macrocyclization reaction takes place considerably more rapidly on a solid support than in solution. The solid phase procedure was successfully used for the construction of cyclic RGD libraries having diverse side chain structures, combined with a variety of ring sizes.

Original languageEnglish
Pages (from-to)2293-2303
Number of pages11
JournalTetrahedron
Volume57
Issue number12
DOIs
Publication statusPublished - 2001 Mar 17

Keywords

  • Cyclic tetrapeptide
  • Heck reaction
  • RGD derivatives
  • Solid phase macrocyclization
  • tert-alcohol resin

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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