Monosaccharides Containing Nitrogen in the Ring, XXXIX. — Synthesis of Analogues of 1,5-Dideoxy-1,5-imino-L-fucitol, Inhibitors of α-L-Fucosidase
Variation of the side chain in the 1,3-dithiane derivative 1 of D-galactose leads to a series of analogues of 1,5-dideoxy-1,5-imino-L-fucitol (deoxyfuconojirimycin) (33), which are potent inhibitors of α-L-fucosidase. Cleavage of the dithioacetal in 5 followed by reduction of the aldehyde 6 and deblocking results in 1,5-dideoxy-1,5-imino-L-galactitol (8). The aldehyde 6 is converted by Wittig reaction to 10 and 14 via 9 and 13, which are homologues of 1,5-dideoxy-1,5-imino-L-fucitol (33). Cyclization of the Wittig product 15 yields the γ-lactam 18. After reduction of the acetylated γ-lactam 19 and subsequent deblocking the trihydroxyindolizidine 24 is obtained, which is an analogue of castanospermine with L-fuco configuration. The chloride 30, which is available from 27, can be converted by intramolecular substitution and removal of the blocking groups to the bicyclic aziridine derivative (3R,4S,5R,6S) -1-azabicyclo[4.1.0]heptane-3,4,5-triol (32). First results on the inhibitory activities of all new analogues on α-L-fucosidase are presented.