Analogues of insulin secretagogue (2S,3R,4S)-4-hydroxyisoleucine:: synthesis by 1,3-dipolar cycloaddition reactions of chiral nitrones to alkenes

(2S,3R,4S)-4-Hydroxyisoleucine, found in fenugreek, is an insulin secretagogue molecule. Non-natural analogues of (2S,3R,4R)- and (2R,3S,4S)-4-hydroxyisoleucine were efficiently prepared by 1,3-dipolar cycloaddition reactions of chiral nitrones derived from either (-)- or (+)-menthone to alkenes. The cycloadducts, obtained via the exo-approach of the alkenes to the nitrone's less hindered face, led after a reductive step and cleavage of the chiral auxiliary, to enantiopure non-natural amino acids in good overall yield. (C) 2008 Elsevier Ltd. All rights reserved.