Anomeric α-azido acid (2-azido-2-deoxy-hept-2-ulopyranosonic acid) derivatives en route to peptides incorporating sugar amino acids

Abstract

Per- O-acylated 2,6-anhydro-aldoheptonic acids of d- glycero- d- gulo and d- glycero- l- manno configuration obtained by nitrosation of the corresponding aldonamides were transformed into methyl-, tert-butyl-, 2,2,2-trichloroethyl-, and pentachlorophenyl esters, acid chlorides and glycinamides by standard procedures. Radical-mediated bromination either by bromine in boiling CHCl 3 under illumination, or NBS in refluxing CCl 4 in the presence of Bz 2O 2 or AIBN, or Na 2S 2O 4–KBrO 3 in CH 2Cl 2–water biphasic solvent mixture at rt gave axial anomers of the 2-bromides of the above esters and acid chlorides (2-bromo-2-deoxy-α- d-hept-2-ulopyranosonic acid derivatives), while a glycinamide was split along the –H 2C–NH– bond. Anomeric bromides of the glycinamides were obtained by N-acylation of a glycine ester with the pentachlorophenyl 2-bromo-2-deoxy-ulosonates. In this reaction the axial anomeric bromide proved stable. Sodium azide in DMSO or DMF was used for the substitution of the anomeric bromides. These reactions proceeded with inversion in the case of each ester and glycinamide to produce equatorial azides (2-azido-2-deoxy-β- d-hept-2-ulopyranosonic acid derivatives). The azide substitution in 2-bromo-2-deoxy-α- d- galacto-hept-2-ulopyranosonic acid chloride gave 2-azido-2-deoxy-α- d- galacto-hept-2-ulopyranosonic acid azide with retention of the anomeric configuration. This acid azide was coupled with a glycine ester to give an axial anomeric azide. These transformations represent highly stereoselective routes to both anomers of dipeptides incorporating anomeric α-azido acids.