2-deoxy-2-(substituted-methyl)analogs of β-Kdop

Abstract Analogs of 3-deoxy- d - manno -octulosonic acid (Kdo) having the β-anomeric hydroxyl group replaced by a substituted-methyl group were prepared from Kdo. The substituted-methyl groups were derived from the carboxyl group of Kdo, whereas the carboxyl group in the analogs was introduced by the stereospecific reaction of the ketose azidomethyl acetate 12d with Me 3 SiCN to give the nitrile 16 . Hydrolysis of the nitrile group of 16 gave the azidocarboxylic acid 17a . Hydrogenation of 17a gave the amino acid 4a . Key steps in the preparation of the 2-hydroxymethyl and 2-phosphonomethyl analogs 4b and 4c , respectively, were the selective reduction of the azidomethyl derivative 17a to the aminomethyl derivative 17b , conversion of 17b by deamination to the β-lactone 19 , and nucleophilic opening of the β-lactone ring of 19 with hydroxide and triethyl phosphite, respectively, to give 4b and 4c . An interesting contrast in the reaction with azide of the methyl and the (methylthio)methyl glycosides of the 1- O -alkylsulfonates 9b and 9f , respectively, was observed. Whereas the former reacted by direct displacement to give the unrearranged azide 9d , the reaction of the latter occurred with sulfur participation to give the rearranged azide 11 .