Practical Enantioselective Approach to 3-Amino-2-Hydroxy Acids and Application to the Synthesis of Natural Products

A practical approach to optically active erythro 3-amino-2-hydroxy acids has been developed and applied to the enantioselective synthesis of 3-phenylisoserine and naturally occurring 3-amino-2-hydroxy-6-methylheptanoic acid (AHMHA), a nonproteinogenic amino acid found in the marine cyclic oligopeptide perthamide C. The proposed synthetic methodology requires the enantioselective Sharpless syn-dihydroxylation of (E)-α,β-unsaturated esters followed by regioselective and stereoselective Mitsunobu azidation on the β-hydroxy group. Subsequent azide hydrogenation and ester hydrolysis provide the desired erythro 3-amino-2-hydroxy acids in high enantiopurity and overall yield. The proposed approach to AHMHA was more efficient and direct compared to the one previously reported in the literature. The absolute configuration of the diol precursor of AHMHA was assigned by ECD analysis of its biphenyl dioxolane, thereby also confirming the absolute configuration of the natural AHMHA.