Stereoselective Synthesis of N‐Glycosyl Amino Acids by Traceless Staudinger Ligation of Unprotected Glycosyl Azides

Abstract

The stereoconservative Staudinger ligation of unprotectedα‐ and β‐glycosyl azides with 2‐(diphenylphosphanyl)‐4‐fluorophenyl esters to afford α‐ and β‐N‐glycosyl amino acids is described. The ligation method works reliably well for unprotected β‐azides of the gluco, galacto and fuco series. Lower yields (ca. 50 %) were obtained with a β‐glucosyl‐N‐acetyl azide. The reaction of an α‐glucosyl azide also led to major improvements compared with the use of non‐fluorinated phosphanes. All the N‐glycosyl amino acid products can be isolated and byproducts removed from the crude reaction mixtures by simple water extraction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Stereoselective synthesis of N-galactofuranosyl amides

“…Similarly, reaction of 2 and Ph 3 P generated an iminophosphorane that epimerized at the anomeric position before reacting with acylating agents, such as pentafluorophenyl valeroate (C 4 H 9 COPFP, Scheme 2). 18 These results are consistent with previous observations by our group [13][14][15]18 and others 19 working on pyranosyl azides.…”

“…If this is the case, the retention of configuration observed with the tetra-O-acetyl azide 2 is even more puzzling. Indeed, as it was observed for pyranosyl azides, 15 the acetylated substrate is expected to undergo ring-opening even more easily than 3, due to the electron withdrawing property of the protecting groups, and thus to afford …”

“…On the contrary, following our previously established protocol, [13][14][15] traceless Staudinger ligation of 2 with 2-diphenylphosphanyl-phenyl valeroate (4a) in a 98:2 N,N-dimethylacetamide (DMA)-1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) solvent mixture (4 h, 70°C) followed by treatment with water afforded the corresponding galactofuranosyl amide 5a in 60% yield as a single anomer (Scheme 3). The structure and anomeric 0008-6215/$ -see front matter Ó 2011 Elsevier Ltd. All rights reserved.…”

“…[13][14][15] In this paper, we describe a simple stereoselective synthesis of Galf amides in both anomeric configurations starting from a common azide precursor. The resulting compounds may be of interest in the generation of new antibacterial leads, or as inhibitors of galactofuranosidases and galactofuranosyltransferases.…”

Staudinger Ligation as a Method for Bioconjugation

“…[96] First, 2-(diphenylphosphino)-5-fluorophenol was coupled to the carboxylic acid moiety of an a-or b-amino acid. In a second step, the Staudinger ligation was performed with unprotected aand b-glycosylazides 76-78 to afford glycosyl amino acids (i.e.…”