SYNTHESIS VIA A CARBOHYDRATE-DERIVED MUNCHNONE OF PYRROLOPYRIDINES (INDOLIZINES) AND IMIDAZOPYRIDINES, AND THEIR EVALUATION AS INHIBITORS OF B-D-GLUCOSIDASES

In the presence of activating agents, the N-acylglycine 8 reacts with electrophilic alkynes via the munchnone 9 to the pyrrolopyridines (= i ndolizines) 10, 18, and 19 (Scheme 1). Depending on the nature of. the activating agent and the reaction temperature, the formation of the p yrroles was accompanied by partial epimerization to the manno-configur ated epimers 16 and 17. The gluco-configurated pyrrolopyridine 10 was deprotected to 12. Silylation of 12, followed by reduction and desilyl ation, gave the hexol 15. Cycloaddition of 9 to 4-toluenesulfonyl cyan ide yielded 53% of the imidazole 23, while cycloaddition to phenyl cya nate gave the phenoxyimidazole 28 in low yields only (Scheme 2). As ex pected, the deprotected pyrroles 12, 15, 20, and 21 are weak inhibitor s of retaining beta-glucosidases, while the deprotected imidazole 24 d erived from 23 proved a good inhibitor of sweet-almond beta-glucosidas es and a powerful inhibitor of Caldocellum saccharolyticum beta-glucos idase.