Chemical Process Synthesis of -Amino Acids and Esters

Abstract

The importance of p-amino acids and esters for the synthesis of potential therapeutic agents and biologically active compounds is well known and the subject of this special issue. This review outlines some of the recent approaches reported for the synthesis of both racemic and enantiomeric p-amino acids and e ters with emphasis on those used for large scale production. This compilation is written from a chemical process perspective focusing on the practical application of these processes for large scale synthesis. A survey of procedures described in patent publications as well as current advances from chemical process research groups and results from our laboratory are included with emphasis on asymmetric Michael-type additions, addition of metal enolates to imines/sulfinimines, classical and enzymatic resolutions, and reduction of enantiomeric enamines.

trans-Cyclopropyl β-Amino Acid Derivatives via Asymmetric Cyclopropanation Using a (Salen)Ru(II) Catalyst

“…The enantioselective synthesis of β-amino acids has recently attracted considerable attention − due to their interesting structural properties and significant pharmacological activities. , β-Amino acids are found in numerous biologically active compounds including β-peptides, − which have been shown to organize into well-defined folded secondary and tertiary structures in aqueous solution, similar to that observed for natural proteins. − β-Amino acids are also crucial structural features of multiple natural products, − β-lactams, and other pharmaceutical candidate compounds. , …”

Pilot Plant Preparation of an αvβ3 Integrin Antagonist. Part 1. Process Research and Development of a (S)-β-Amino Acid Ester Intermediate: Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction

“…Asymmetric Enamine Reduction Approach to 3. Chiral reduction of an appropriately functionalized prochiral enamine was also investigated as a logical method to access a single enantiomer of 3 . The chemistry employed to ascertain the feasibility of such an approach is outlined in Scheme .…”

Organocatalytic Synthesis of N-Phenylisoxazolidin-5-ones and a One-Pot Synthesis of β-Amino Acid Esters

“…We report here a novel method for C−N bond formation by the reaction of α,β-unsaturated aldehydes with nitrosobenzene using N -heterocyclic carbene (NHC) catalysis, forming N -phenylisoxazolidin-5-ones that are converted to the corresponding N - p -methoxyphenyl ( N -PMP)-protected β-amino acid esters in a mild one-pot synthetic protocol. β-amino acids possess biologically important properties, occur in natural products, and are key building blocks to several bioactive compounds …”