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 of highly stereoselective reaction sequences involving, as the key steps, an internal amidomercuration (alpha-epimer) and a double reductive amination (beta-epimer). alpha-Homogalactonojirimycin retains a large part of the potent activity of the parent galactonojirimycin and 1-deoxygalactonojirimycin as an inhibitor of alpha-galactosidases. However, by contrast with the parent iminosugars, it does not inhibit beta-galactosidases, with the exception of the Jack beans enzyme. beta-Homogalactonojirimycin is a weak alpha-galactosidase inhibitor and is completely devoid of activity towards beta-galactosidases. Thus, a marked selectivity toward one family of enzymes has been achieved by the addition of an alpha-CH(2)OH group in the structure of the parent iminosugars.