Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

Abstract

Chiral amino acids (AAs), being the main "building" blocks of the living organisms, are also an important class of organic compounds which broadly applied in synthetic chemistry, biochemistry, catalysis and the designing of new drugs. According to the industrial-commodity market, chiral non-proteinogenic AAs containing various functional groups come to the fore. To date, radical cross-coupling reactions are becoming an option as an attractive powerful tool for AA syntheses. Owing to mild reaction conditions and high functional-group tolerance, radical chemistry represents an ideal strategy for the synthesis of challenging complex non-proteinogenic AAs. Moreover, the radical cross-coupling allows introducing AA residue into drug scaffolds and natural compounds. In the present review, we wish to summarize and discuss all the reported to date methods of the asymmetric synthesis of AAs using radical chemistry by presenting a comprehensive account of the literature in this field going back to 1990. We especially emphasize on a radical chemistry approach and, exclusively, on stereoselective synthesis of various α-, β-, γ-AAs and derivatives employing a different type of radical initiators starting from AIBN and organostannes and ending with powerful photoredox catalysis. Furthermore, the mechanism of the reported reactions will be discussed. Radicals Generated from AA Derivatives in Conjugate Additions 6.1. Radicals Generated from α-Substituted Glycine Derivatives in AA Synthesis 6.2. Modification of Chiral AA Side Chain by Radical Chemistry 7.

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.…”

Asymmetric Synthesis of Perfluoroalkylated α‐Amino Acids through Generated Radicals Using a Chiral Ni(II) Complex

“…To date, there exist a plethora of methods for the synthesis of FAAs, [19–23] however, the approaches for obtaining of PFAAs are still rare, especially in an enantioselective manner [24,25] . As a consequence, only several selective examples of asymmetric synthesis of PFAAs have been reported to date [26–33] .…”

“…[17,18] To date, there exist a plethora of methods for the synthesis of FAAs, [19][20][21][22][23] however, the approaches for obtaining of PFAAs are still rare, especially in an enantioselective manner. [24,25] As a consequence, only several selective examples of asymmetric synthesis of PFAAs have been reported to date. [26 -33] For example, Yajima et al have utilized photoinduced diastereoselective addition of perfluoroalkyl iodides to acrylic acid derivatives bearing chiral auxiliaries for the synthesis of PFAAs, however the requirement of the chiral auxiliaries which can't be recovered, and the formation of organic waste materials after the hydrolysis of AA derivatives make this protocol challenging for large scale production.…”

Synthesis and redox activity of carbene-coordinated group 13 metal radicals

“…Radicals are important species in organic synthesis, 1 polymer 2 and plasma chemistry 3 and in bioorganic chemistry. 4 They typically tend to dimerize, hence kinetic stabilization by use of sterically demanding ligands or electronic stabilization by delocalization of the unpaired electron are major stabilizing strategies. In recent years, main group element radicals received increasing interest due to their unique physical and chemical properties, 5 and several bulky and/or π-conjugated ligands were established which allowed for the isolation of electronically and sterically stabilized reactive radicals.…”