Mimicking Nature to Make Unnatural Amino Acids and Chiral Diamines

Abstract

Biomimetic studies of pyridoxal and pyridoxamine models are of both fundamental and practical interest. This review examines (i) deracemization of alpha-amino acids with a chiral pyridoxal model, (ii) sensing of chirality of small molecules including alpha-, beta-, and gamma-amino acids, peptides, amino alcohols and diamines with an achiral pyridoxal model and (iii) stereospecific synthesis of chiral diamines with a chiral pyridoxamine model. A binol-based aldehyde is useful as a chiral pyridoxal model to deracemize a variety of alpha-amino acids to make D-amino acids. 2,2'-Dihydroxybenzophenone is useful as an achiral pyridoxal model for sensing the chirality of the above-mentioned small molecules in a unified way. Bis(2-hydroxyphenyl)-ethylenediamine (hpen) is useful as a chiral pyridoxamine model for making chiral diamines. Weak forces (H-bonding, steric and electronic effects) involved in transamination reactions with pyridoxamine for the synthesis of amino acids are compared with those for the diaza-Cope rearrangement reaction with hpen for the synthesis of chiral diamines. Both experimental and computational methods are used to analyze the biomimetic systems.