Stereoselective synthesis of quaternary α-amino acids. Part 1: Acyclic compounds

Dynamic kinetic resolution

https://users.ox.ac.uk/~dplb0149/publication/NPRBiocatalysisRev.pdf

Biocatalysis and enzymes in organic synthesis

Preparative biotransformations: the employment of enzymes and whole-cells in synthetic organic chemistry

The sperm whale myoglobin active site mutants (L29H/H64L and F43H/H64L Mb) have been shown to catalyze the asymmetric oxidation of sulfides and olefins. Thioanisole, ethyl phenyl sulfide, and cis -β-methylstyrene are oxidized by L29H/H64L Mb with more than 95% enantiomeric excess (% ee). On the other hand, the F43H/H64L mutant transforms trans -β-methylstyrene into the trans -epoxide with 96% ee. The dominant sulfoxide product in the incubation of alkyl phenyl thioethers is the R isomer; however, the mutants afford dominantly the S isomer of aromatic bicyclic sulfoxides. The results help us to rationalize the difference in the preferred stereochemistry of the Mb mutant-catalyzed reactions. Furthermore, the Mb mutants exhibit an improvement in the oxidation rate up to 300-fold with respect to wild type.

Asymmetric oxidation catalyzed by myoglobin mutants

The enzyme (lipases and chymotrypsin)-catalyzed hydrolysis of Schiff bases derived from racemic amino acid esters and aromatic aldehydes has been investigated. The reactions were successfully carried out in different aqueous organic solvents at ambient temperature, but the aqueous acetonitrile (5.4% water content by volume) was the solvent of choice. The l-amino acid (ee 98%) precipitated out from the solution as the reaction progressed, and the liberated aldehyde and unhydrolyzed d-ester (ee 40−98%) remained in the solution. The range of substrates included amino acids having different types of side chains. The addition of an organic base (DABCO) into the solution resulted in the racemization of the remaining d-ester and the additional hydrolysis of the substrate, thus leading to the effective asymmetric transformation of the initial ester. Upto 87.5% of the initial racemate was converted into the l-enantiomer.

Schiff Bases of Amino Acid Esters as New Substrates for the Enantioselective Enzymatic Hydrolysis and Accompanied Asymmetric Transformations in Aqueous Organic Solvents1,2

/pdf/synthetic-and-biotransformation-studies-on-prochiral-non-44yqhicctp.pdf

Synthetic and biotransformation studies on prochiral non-proteinogenic amino acids: Diethyl α-acetamido, α-alkylmalonates

Nine diethyl a-acetamido, a-alkylmalonates 3-1 1 (alkyl=methyl, benzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6difluorobenzyl, 3-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 2-chlorobenzyl and 3-chlorobenzyl) have been synthesised in three steps starting with diethyl malonate in overall yields of 49-90%. The structures of C-alkylated acetamidomalonates have been established on the basis of their spectral data, the structures of two compounds 9 and 1 1 are also confirmed on the basis of their X-ray crystallographic studies. Further, the X-ray crystal structure of the chiral monoethyl ester of a-acetamidomalonic acid 1 has been studied. None of our C-alkylated acetamidomalonate has been found to be a substrate for lipase-catalysed enantiodifferentiating deesterification! hydrolysis of the symmetric diester groups.

Amarjit Singh

Papers

Schiff Bases of Amino Acid Esters as New Substrates for the Enantioselective Enzymatic Hydrolysis and Accompanied Asymmetric Transformations in Aqueous Organic Solvents1,2

Synthetic and biotransformation studies on prochiral non-proteinogenic amino acids: Diethyl α-acetamido, α-alkylmalonates

Synthetic and Biotransformation Studies on Prochiral Non-proteinogenic Amino Acids: Diethyl α-Acetamido, α-Alkylmalonates.