Total synthesis of the cyclic biphenyl ether peptides K-13 and OF494-III via S(N)Ar macrocyclizations of peptidyl ruthenium π-arene complexes

James W. Janetka, Daniel H. Rich

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95 Scopus citations

Abstract

Intramolecular nucleophilic aromatic substitution (S(N)Ar) of preformed ruthenium cyclopentadienyl cationic peptidyl π-complexes forms cyclic biphenyl ethers in convenient, high-yielding reactions. The utility of the method was demonstrated by the efficient convergent total synthesis of two natural products, K-13 and OF4949-III. Several analogs of K-13 and OF4949-I-IV were synthesized in high yields, and one ring system that could not be prepared by a macrolactamization method was formed in high yield by biaryl ether formation from peptidyl ruthenium complexes. Direct comparisons between these two approaches are provided. Transition metal π-complexes of either N-protected or carboxyl-protected amino acids can be used as coupling partners in peptide coupling reactions. Preformed peptidyl ruthenium complexes can be used to synthesize cyclic biphenyl ethers in a combinatorial fashion.

Original languageEnglish
Pages (from-to)6488-6495
Number of pages8
JournalJournal of the American Chemical Society
Volume119
Issue number28
DOIs
StatePublished - Jul 16 1997

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