A Facile Synthesis of -N-Ribosyl-Asparagine and -N-Ribosyl-Glutamine Building Blocks

Glycosylated peptides have a fundamental role in biological systems: in fact, more than half of all proteins carry carbohydrate moieties, generating different glycoforms whose exact composition often controls protein function and distribution in biological systems [1]. The details of glycan regulation of protein activity and stability are still under intense scrutiny and the synthesis of welldefined glycopeptides is therefore an important target [2], which still presents many challenges to organic chemistry. One of the processes that is currently been elucidated is adenosine diphosphate ribosylation (ADP-ribosylation), a wide-occurring post-translational modification effected by enzymes that transfer ADP-ribose from NAD + to Asn, Glu, Asp, Arg or Cys residues of proteins, so altering their function [3]. Elucidation of ADP-ribosylation events would benefit greatly from the availability of well-defined ADP-ribosylated peptides and analogues thereof. In this paper we present a novel approach to the chemical synthesis of ribosylated amino acid building blocks using traceless Staudinger ligation. We describe an efficient and stereoselective synthesis of -N-ribosyl-asparagine (-N-ribosyl-Asn)and -N-ribosyl-glutamine (-N-ribosyl-Gln) building blocks starting from 5-tertbutyldiphenylsilyl-β-D-ribofuranosyl azide. The N-glycosyl aminoacids are produced in good yields as pure -anomers, suitably protected for peptide synthesis. 1. a) Varki, A. Glycobiology 1993, 3, 97-130. b) Dwek, R. A. Chem. Rev. 1996, 96, 683-720. c) Reuter, G.; Gabius, H.J. Cell. Mol. Life Sci. 1999, 55, 368-422. d) Gamblin, D. P.; Scanlan, E. M.; David, B. G. Chem. Rev. 2009, 109, 131-163. 2. a) Marcaurelle, L. A.; Bertozzi, C. R. Glycobiology 2002, 12 (6), 69R-77R. b) Warren, J. D.; Miller, J. S., Keding, S. J.; Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, 6576. 3. Corda, D.; Di Girolamo, M. EMBO J. 2003, 22, 1953-1958.