Prev. Article Next Article Table of Contents

Article

Synthesis of the Side Chain Cross-Linked Tyrosine Oligomers Dityrosine, Trityrosine, and Pulcherosine

Supporting Info

Ojia Skaff,^† Katrina A. Jolliffe,^† and Craig A. Hutton*^†^‡^§

School of Chemistry, The University of Sydney, NSW 2006, Australia, School of Chemistry, The University of Melbourne, VIC 3010, Australia, and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia

J. Org. Chem., 2005, 70 (18), pp 7353–7363

DOI: 10.1021/jo051076m

Publication Date (Web): August 10, 2005

†

The University of Sydney.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

‡

School of Chemistry, The University of Melbourne.

Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne.

, chutton@unimelb.edu.au

Abstract

An efficient synthesis of dityrosine and the first syntheses of the tyrosine trimers trityrosine and pulcherosine have been achieved. Protected 3-iodotyrosine underwent tandem Miyaura borylation−Suzuki coupling to give protected dityrosine. The choice of benzyl carbamate, ester, and ether protecting groups enabled a one-step global deprotection to give dityrosine. Suzuki coupling of protected 3,5-diiodotyrosine and tyrosine-3-boronic acid derivatives gave the corresponding trityrosine, but in low yield. However, use of a potassium tyrosine-3-trifluoroborate derivative in place of the corresponding pinacol boronate ester, in combination with protecting group variation, gave protected trityrosine in good yield. Access to pulcherosine was achieved through copper-catalyzed coupling of phenylalanine-4-boronic acid and 4-O-protected dopa derivatives to give an isodityrosine derivative. Selective halogenation followed by Suzuki coupling with the potassium tyrosine-3-trifluoroborate gave protected pulcherosine. Global deprotection of the protected trityrosine and pulcherosine derivatives completed the first syntheses of the corresponding tris-α-amino acids.

View: Full Text HTML | Hi-Res PDF