alpha- and beta-homogalactonojirimycins (alpha- and beta-homogalactostatins): Synthesis and further biological evaluation

The homoiminosugars alpha- and beta -homogalactonojirimycins were prepared from a common intermediate, tetra-O-benzyl-D-galacto-heptenitol 6, by way o f highly stereoselective reaction sequences involving, as the key steps, an internal amidomercuralion (a-epimer) and a double reductive amination (bet a -epimer). alpha -Homogalactonojirimycin retains a large part of the poten t activity of the parent galactonojirimycin and 1-deoxygalactonojirimycin a s an inhibitor of alpha -galaclosidases. However, by contrast with the pare nt iminosugars, it does not inhibit beta -galactosidases, with the exceptio n of the Jack beans enzyme. beta -Homogalactonojirimycin is a weak cc-galac tosidase inhibitor and is completely devoid of activity towards P-galactosi dases. Thus, a marked selectivity toward one family of enzymes has been ach ieved by the addition of an alpha -CH2OH group in the structure of the pare nt iminosugars. (C) 2001 Elsevier Science Ltd. All rights reserved.