New C-Glycosylated α-Amino Acid Synthesis by Addition Reaction of an Amino Acid Organozinc Reagent on Carbohydrate-Derived Aldehydes

Abstract

Two unreported C-glycosylated amino acid structures could be prepared by addition of an amino acid organozinc on carbohydrates bearing an aldehyde function. For this purpose, a new iodinated amino acid bearing a four-carbon side chain was conveniently prepared in two steps. Conversion into the corresponding organozinc reagent was optimal in acetonitrile using zinc/copper activated with 1,2-dibromoethane and trimethylsilyl chloride. A protocol was developed for the addition of this organozinc compound to simple aldehydes in acetonitrile using BF₃ · OEt₂ as a Lewis acid. When applied to riboside and glucoside aldehyde derivatives, this protocol led to new C-glycosylated amino acids in acceptable yields.

GRAPHICAL ABSTRACT

Keywords:

• Amino acid
• C-glycosylated amino acid
• organozinc

ACKNOWLEDGMENTS

This work was supported Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche, as well as the Fondation Recherche Médicale. We are grateful to Pierre Sanchez and Maryse Béjaud for performing LC-MS and NMR analyses, respectively. We thank Pr William D. Lubell for constructive comments on the manuscript.