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Several polyhydroxyperhydroazepines have been obtained either by chemoenzymatic or chemical synthesis. Condensation of (±)-3-azido-2-hydroxypropanaldehyde and dihydroxyacetone phosphate (DHAP) in the presence of a DHAP dependent aldolase followed by treatment with acid phosphatase and an isomerase gave a 6-azido-6-deoxyaldopyranose, which upon reductive 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 leads to a meso-3,4,5,6-tetrahydroxyperhydroazepine, d-mannose to a derivative with a C 2 symmetry axis, and N-acetylglucosamine to a 6-acetamidoiminocyclitol. Asymmetrization of the meso azasugar was carried out by chemical means, to yield a 3-methoxy-4,5,6-trihydroxyazepane. An attempted enzymatic synthesis of the methoxy derivatives of these azasugars was unsuccessful, leading, however, to both enantiomers of 1-deoxy-2-O-methylmannojirimycin. Some of these compounds display significant activity as glycosidase inhibitors, with K i values from moderate to 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 pseudochair conformation.

Several sialyl Lewis X (SLex) mimics that contain the essential functional groups for receptor interaction and a negative charge or a hydrophobic group have been developed as inhibitors of E-, P-, and L-selectins. Some of the mimics exhibit selectin inhibition activities 103−104-fold more potent than does the natural ligand tetrasaccharide, with IC50 in the low micromolar to high nanomolar range. The syntheses of these mimics are relatively simple, using TMSOTf-Ac2O mediated C-glycosylation with concurrent selective deprotection of the primary benzyl group and enzymatic aldol addition reactions as key steps.

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