A Nitro Sugar-Mediated Stereocontrolled Synthesis of β2-Amino Acids: Synthesis of a Polyhydroxylated trans-2-Amino­cyclohexanecarboxylic Acid†

The first stereocontrolled nitro sugar-mediated synthesis of polyhydroxylated β-amino acids and their incorporation into peptides is described. The key steps of this approach are a Michael addition of the lithium salt of tris(phenylthio)methane (a carboxyl synthetic equivalent) to sugar nitro olefins, and the reduction of the nitro group to an amino group. Specifically, two glyceraldehyde-based β-amino acids and a polyhydroxylated cyclohexyl β-amino acid were prepared. The latter, which could act as a water-soluble mimic of the proline-glycine δ-turn, was easily transformed into the corresponding 5-amino-6-(hydroxymethyl)cyclohexane-1,2,3,4-tetraol, a novel amino-carbasugar. However, this did not show significant glycosidase inhibiting properties.