Stereoselective Synthesis of (2<i>S</i>,3<i>R</i>)‑α-Hydroxy-β-Amino Acids (AHBAs): Valinoctin A, (2<i>S</i>,3<i>R</i>)‑3-Amino-2-Hydroxydecanoic Acid, and a Fluorescent-Labeled (2<i>S</i>,3<i>R</i>)‑AHBA

Abstract

We report the stereoselective synthesis of an alkynyl side-chain containing (2<i>S</i>,3<i>R</i>)-α-hydroxy-β-amino acid ((2<i>S</i>,3<i>R</i>)-AHBA) analogues. The Cu­(I)-catalyzed reactions of (<i>R</i>)-glyceraldehyde acetonide and dibenzylamine with terminal alkynes provided the corresponding (2<i>S</i>,3<i>R</i>)-α-amino alcohols with good-to-excellent diastereoselectivity. Subsequent chemical transformations provided easy access to the alkynyl side-chain containing (2<i>S</i>,3<i>R</i>)-AHBAs. The utility of the methodology was demonstrated by the stereoselective synthesis of valinoctin A and (2<i>S</i>,3<i>R</i>)-3-amino-2-hydroxy­decanoic acid ((2<i>S</i>,3<i>R</i>)-AHDA). Photophysical properties and cell permeability of a pyrene-labeled (2<i>S</i>,3<i>R</i>)-AHBA were also determined