Studies on the synthesis of (2S,3R)-3-hydroxy-3-methylproline via C2-N bond formation.

A new efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) is reported. During the course of a recent study on the Lewis acid promoted intramolecular opening of an epoxide by a carbamate NH, a highly concerted rearrangement was unexpectedly observed. Further investigations of substrate generality show that delta-carbamate-alpha,beta-epoxide esters commonly underwent similar rearrangements with the aid of Lewis acids. Retrosynthetic analysis of such a C(2)-N disconnection can lead to an efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) in high enantio purity. Stereochemistries were established by a Sharpless asymmetric dihydroxylation and a diastereoselective reductive amination.

Enantioselective synthesis of (2S,3R)-3-hydroxy-3-methylproline, a novel amino acid found in polyoxypeptins.

The enantioselective synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) was achieved by the Sharpless AD, regioselective opening of cyclic sulfate by NaN(3) and intramolecular ring-closing reaction. The reported route has the advantage of a high overall yield and good enantiomeric purity, as well as starting from readily available chemical substrates and inexpensive reagents.