A comparative study of the O-3 reactivity of isomeric N-dimethylmaleoyl-protected d-glucosamine and d-allosamine acceptors

Four isomeric N-dimethylmaleoyl 4,6-O-benzylidene-protected d-hexosamine acceptors (2, 3, 4, and 5) with all possible configurations at C-1 and C-3 (e.g., derived from d-glucosamine and d-allosamine) were prepared, and the assessment of their O-3 relative reactivity through competition experiments using the known per-O-acetylated d-galactopyranosyl trichloroacetimidate donor (15) was then carried out. The reactivities are in the order 4 ? 2 > 5 > 3. The analysis of the NMR spectra of 2–5 at different temperature and modeling experiments carried out on analogs of 2–5 (DFT) and on the acceptors themselves (MM) are coincident, and have helped to establish the stability of the different hydrogen bonds, and of the conformers which carry them. The whole results suggest that the electronic effects (hydrogen bonds) are required to explain the observed trend, in spite of the axial conformation of the most reactive hydroxyl group. The steric effects appear only when hydrogen bonds are weak.