A new synthesis of polyhydroxylated cyclopentane beta-amino acids from nitro sugars

The design and synthesis of new amino acids a has attracted considerable attention in recent times. Particular attention has been devoted to b-amino acids, on account of the metabolic and conformational stability of b‑peptides. Among them, cyclopentane b-amino acids have become attractive candidates for the stabilization of bioactive peptides, due to the high propensity of their homopolymers to fold in rigid secondary structures in short peptide sequences.

Nitro compounds are very versatile in organic synthesis. In particular, nitroalkenes can act as potent Michael acceptors and, in fact, Michael addition of nucleophiles to nitroolefins is an important tool for the creation of carbon-carbon bonds and heteroatom-carbon bonds. After employing this powerful method for carbon-carbon bond construction, the nitro group can be transformed into a wide variety of functionalities, including amino groups, by reduction.

In connection with our continuing interest in nitro compounds and cycloalkane b-amino acids, we report here the unexplored Michael addition of tris(phenylthio)methane (a synthetic equivalent of the carboxyl group) to a cyclopentane sugar nitroolefin derived from D-glucose ([1R, 2R)-2-(benzyloxy)-4-nitrocyclopent-3-en-1-yl formate], this being the key step in a synthetic sequence that allowed new access to a cyclopentane b-amino acid [methyl (1S,2R,3R,5R)-2-(benzyloxy)-5-((tert-butoxycarbonyl)amino)-3-hydroxycyclopentane-1-carboxylate]. This approach is shorter and more efficient than a previous synthesis of this b-amino acid, also obtained from D-glucose.