Synthesis of 3,3′-neotrehalosadiamine and related 1,1′-aminodisaccharides using disarmed, armed, and superarmed building blocks

Here we report a high yielding, stereoselective synthesis of the naturally occurring 1,1′-disaccharide neotrehalosadiamine (NTD) and some related analogs. Following an eleven-step sequence, seven of which did not require chromatographic separation, NTD was generated in 60% overall yield from the inexpensive, commercially available precursor 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose. The key α,β-linkage of NTD was formed in a highly stereoselective manner by taking advantage of the participating effect of the acyl group at O-2 of the donor glycoside. The influence of electronic effects of disarmed, armed, and superarmed glycosyl donors and acceptors on the outcome of 1,1′-glycosidation was also observed. Antibacterial studies using NTD and its analogs show detectable but weak anti-staphylococcal activity.