Monosaccharide mit Stickstoff im Ring, XXXIX. Synthese von modifizierten α‐ L ‐Fucosidase‐Inhibitoren, die 1,5‐Didesoxy‐1,5‐imino‐ L ‐fucit als Basisstruktur enthalten

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.