Norbornane Mimics of Distorted β ‐ D ‐Glucopyranosides – Inhibitors of β ‐ D ‐Glucopyranosidases?

The racemic gluco ‐configured norbornanes 4 and 16 were prepared and tested as inhibitors of β‐ glucosidases. The known alcohol 5 was deprotected to provide the triol 6 . Silylation (→  7 ), monobenzoylation (→  8 / 9 ), and oxidation provided the regioisomeric ketones 10 and 11 . Reduction of 10 gave the desired endo ‐alcohol 13 , albeit in low yield, while reduction of the isomeric ketone 11 provided mostly the altro ‐configured endo ‐alcohol 12 . The alcohol 13 was desilylated to 14 . Debenzoylation to 15 followed by hydrogenolytic deprotection gave the amino triol 4 that was reductively aminated to the benzylamine 16 . The amino triols 4 and 16 proved weak inhibitors of the β ‐glucosidase from Caldocellum saccharolyticum ( 4 : IC 50  = 5.6 m m; 16 : IC 50  = 3.3 m m) and from sweet almonds ( 16 : IC 50  = 5.5 m m) . A comparison of 4 with the manno ‐configured norbornane 3 shows that 3 is a better inhibitor of snail β ‐mannosidase than 4 is of β‐ glucosidases, in keeping with earlier results suggesting that these β ‐glycosidases enforce a different conformational itinerary.