5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease.

Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-D-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.

Synthesis and Properties of Bridgehead-Functionalized Permethylbicyclo[2.2.2]octasilanes.

A series of previously unknown bridgehead-functionalized bicyclo[2.2.2]octasilanes, MeSi-SiMe-X, X-SiMe-X, and X-SiMe-Y [X, Y = -SiMe Ph ( = 1, 2) (, , ), -SiMeFc (Fc = ferrocenyl) (, , , ), -COR (R = Me, Bu) (, , ), COOMe (), COOH ()], have been prepared by the reaction of the silanides MeSi-SiMeK or KSiMeK with proper electrophiles and fully characterized.