F. Morisvaras et al., ENZYMATIC CHEMICAL SYNTHESIS AND BIOLOGICAL EVALUATION OF 7-MEMBERED IMINOCYCLITOLS/, Journal of the American Chemical Society, 118(33), 1996, pp. 7647-7652
Several polyhydroxyperhydroazepines have been obtained either by chemo
enzymatic or chemical synthesis. Condensation of (+/-)-3-azido-2-hydro
xypropanaldehyde and dihydroxyacetone phosphate (DHAP) in the presence
of a DHAP dependent aldolase followed by treatment with acid phosphat
ase and an isomerase gave a 6-azido-6-deoxyaldopyranose, which upon re
ductive amination afforded the title compound. The iminocyclitols can
also be obtained by chemical manipulations of aldopyranoses, protected
as benzyl glycosides or diisopropylidene ethers. Thus, D-galactose le
ads to a meso-3,4,5,6-tetrahydroxyperhydroazepine, D-mannose to a deri
vative with a C-2 symmetry axis, and N-acetylglucosamine to a 6-acetam
idoiminocyclitol. Asymmetrization of the mesio azasugar was carried ou
t by chemical means, to yield a 3-methoxy-4,5,6-trihydroxyazepane. An
attempted enzymatic synthesis of the methoxy derivatives of these azas
ugars was unsuccessful, leading, however, to both enantiomers of 1-deo
xy-2-O-methylmannojirimycin. Some of these compounds display significa
nt activity as glycosidase inhibitors, with K-i values from moderate t
o low micromolar range. Though all these iminocyclitols do not inhibit
the mechanistically related HIV protease, the 3,6-dibenzyl derivative
30 showed moderate inhibition. The X-ray structure of 7 indicates a p
seudochair conformation.