Synlett 2003(10): 1411-1414
DOI: 10.1055/s-2003-40820
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile Two-Step Synthesis of Novel Ring-A Double Substituted Tryptophan Building Blocks for Combinatorial Chemistry

Sofia Gorohovskya, Simcha Meira, Vladimir Shkouleva, Gerardo Bykb, Garry Gellerman*a
a Compugen Ltd., Chemistry Division, 11 Ha’Amal St., P.O.Box 3066, Ashkelon 78785, Israel
b Laboratory of Peptidomimetics and Genetic Chemistry, Department of Chemistry, Bar Ilan University, 52900-Ramat Gan, Israel
e-Mail: garyg@compugen.co.il.;
Further Information

Publication History

Received 31 March 2003
Publication Date:
24 July 2003 (online)

Abstract

A fast synthesis of ring-A disubstituted Fmoc and Boc protected l-tryptophan analogs was achieved starting from the appropriate 2,4- or 2,3-disubstituted phenylhydrazines and optically active N,N-diprotected l-glutamic acid γ-aldehydes, utilizing a Fischer-indole synthesis as a key step. Unlike most of the previously reported methods, that required the multistep stereoselective generation of a chiral carbon, this fast methodology is useful for generating optically active ring-A disubstituted protected tryptophans starting from a simple and common chiral precursor. These building blocks have a wide application scope in peptide and combinatorial chemistry fields.