Asymmetric synthesis of (S)‐α‐(octyl)glycine via alkylation of Ni(II) complex of chiral glycine Schiff base

Abstract

Over last decade, the use of Ni(II) complexes, derived from of glycine Schiff bases with chiral tridentate ligands, has emerge as a leading methodology for preparation of structurally diverse Tailor‐Made Amino Acids, the key structural units in modern medicinal chemistry, and drug design. Here, we report asymmetric synthesis of derivatives of (S)‐α‐(octyl)glycine ((S)‐2‐aminodecanoic acid) and its N‐Fmoc derivative via alkylation of chiral nucleophilic glycine equivalent with n‐octyl bromide. Under the optimized conditions, the alkylation proceeds with excellent yield (98.1%) and diastereoselectivity (98.8% de). The observed stereochemical outcome and convenient reaction conditions bode well for application of this method for large‐scale asymmetric synthesis of (S)‐2‐aminodecanoic acid and its derivatives.

Comparative study of different chiral ligands for dynamic kinetic resolution of amino acids

“…The major conclusion of this work is the imminently better performance of ligand 11 over nonsubstituted analog 10 and α‐Me‐proline‐derived ligands 12 and 13 . These results are fully consistent with previously reported data on alkylation 45,78–80 and Michael additions 81,82 of glycine and dehydroalanine Schiff base Ni(II) complexes derived from various chiral ligands including 11 . Rationale for the enhanced stereocontrolling properties of 11 was previously deduced from extensive analysis of crystallographic data showing parallel displaced type of aromatic interactions between the selectively chlorinated o ‐amino‐benzophenone and Pro N ‐ m ‐, p ‐dichloro‐benzyl rings 83 .…”

New pharmaceuticals approved by FDA in 2020: Small‐molecule drugs derived from amino acids and related compounds

“…In this regard, we would like to stress the growing need in availability and affordability of various tactual types of AAs. Indeed, the interest in the development of synthetic approaches for the preparation of tailor‐made AAs in enantiomerically pure form is currently at an all‐time high 82–135 . Some impressive developments have been made in the area of dynamic kinetic resolution of unprotected AAs, 136–139 a methodology which is best suited for large‐scale production and can rival biocatalytic approaches in affordability and low‐cost structure.…”