Michael Anders Godskesen

Deoxyiminoalditols from aldonolactones--V. Preparation of the four stereoisomers of 1,5-dideoxy-1,5-iminopentitols. Evaluation of these iminopentitols and three 1,5-dideoxy-1,5-iminoheptitols as glycosidase inhibitors.

The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-amino-5-deoxy-1,5-lactams, 2, 8, 12 and 17, respectively. Reduction of the lactam function using sodium borohydride/acetic or trifluoroacetic acid, or borane dimethyl sulfide complex yielded the iminopentitols. The compounds 3, 9, 13 and 18, together with the three 1,5-dideoxy-1,5-iminoheptitols 19,20 and 21 were tested for inhibition of the glycosidase activities present in an extract from human liver. Compound 18 was a potent and 19 a moderately good inhibitor of beta-glucosidase. Compound 3 together with 19, 20 and 21, all having D-arabino-configuration at the hydroxy-substituted carbon atoms, were good inhibitors of alpha-L-fucosidase.

Synthesis and evaluation of a 5-membered isoiminosugar as glycosidase inhibitor

Abstract (3 R , 4 R )-4-hydroxy-3-hydroxymethylpyrrolidine ( 6 ) was prepared from d -xylose and found to be a weak inhibitor of α- d -, β- d -glucosidase and α- l -fucosidase.

Unusual ring contraction by substitution of 4-O-activated-pentono-1,5-lactams with cyanide. Stereospecific synthesis of 6-amino-1,4,5,6-tetradeoxy-1,4-imino-hexitols

Abstract Reaction of 4-O-sulfonylated 2,3-O-isopropylidene- d -ribo- or - d -lyxo-1,5-lactams with tetrabutylammonium cyanide gave 4-amino-5-C-cyano-4,5-dideoxy-2,3-O-isopropylidene- l -lyxo-5 or - l -ribo-15-1,4-lactams, respectively. A stereospecific ring contraction with inversion at C-4 had taken place in each case. Reduction of the cyano-lactams with LiAlH4 gave 6-amino-1,4,5,6-tetradeoxy-1,4-imino- l -lyxo-6 or - l -ribo-16-hexitol, respectively. The 6-amino-1,4,5,6-tetradeoxy-1,4-imino- l -ribo-hexitol 16 was found to be a moderate inhibitor of α- l -fucosidase with a Ki of 110 μM.