106. Synthesis via a carbohydrate-derived Munchnone of pyrrolopyridines (indolizines) and imidazopyridines, and their evaluation as inhibitors of β- D-glucosidases

In the presence of activating agents, the N-acylglycine 8 reacts with electrophilic alkynes via the munchnone 9 to the pyrrolopyridines (= indolizines) 10, 18, and 19 (Scheme 1). Depending on the nature of the activating agent and the reaction temperature, the formation of the pyrroles was accompanied by partial epimerization to the manno-configurated epimers 16 and 17. The gluco-configurated pyrrolopyridine 10 was deprotected to 12. Silylation of 12, followed by reduction and desilylation, gave the hexol 15. Cycloaddition of 9 to 4-toluenesulfonyl cyanide yielded 53% of the imidazole 23, while cycloaddition to phenyl cyanate gave the phenoxyimidazole 28 in low yields only (Scheme 2). As expected, the deprotected pyrroles 12, 15, 20, and 21 are weak inhibitors of retaining β-glucosidases, while the deprotected imidazole 24 derived from 23 proved a good inhibitor of sweet-al-mond β- glucosidases and a powerful inhibitor of Caldocellum saccharolyticum β- glucosidase.