ISSN:
0170-2041
Keywords:
Deoxyfuconojirimycin
;
Amino sugars
;
Indolizidine derivatives
;
Fucosidase inhibitors
;
Carbohydrates
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Monosaccharides Containing Nitrogen in the Ring, XXXIX. - Synthesis of Analogues of 1,5-Dideoxy-1,5-imino-L-fucitol, Inhibitors of α-L-FucosidaseVariation 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.
Additional Material:
1 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jlac.1990199001176
