An improved enzymatic method for the preparation of (R)-phenylacetyl carbinol

Abstract

(R)-Phenylacetyl carbinol (R-PAC) is one of the key chiral a-hydroxyketones utilized as a synthon in the synthesis of a number of pharmaceuticals having a-and b-adrenergic properties. An improved procedure for the preparation of the compound using the glutathione S-transferase-tag fused catalytic subunit of Escherichia coli acetohydroxyacid synthase I as a catalyst was established in this study. The results showed that under the optimized conditions the target molecule was able to be obtained with an isolated yield of 80.6% and an ee value of higher than 98%. This method could not only ease the preparation of R-PAC, but promote the synthetic applications of E. coli AHAS I as well.

Expedient Synthesis of a Metallostibine Os2(CO)8(µ‐SbPh): An Unusual and Strong Two‐Electron‐Donor Ligand

“…We recently reported the synthesis of an osmium-antimony carbonyl cluster, Os 3 (CO) 11 (μ 3 -SbPh)(Cl) 2 (1). [14] This cluster can be viewed as an adduct of a metallostibine, Os 2 (CO) 8 (μ-SbPh), (2), with an electron-deficient Os(CO) 3 (Cl) 2 fragment. We reasoned that it may be possible to release 2 if it were substituted by other two-electron donors.…”

“…Compound 1 was prepared through an adapted method from the literature. [14] Tungsten complexes 5a-f were prepared according to a literature method. [30] All activated neutral, basic, and weakly acidic γ-Al 2 O 3 (Brockmann activity I, particle size: 150 mesh, pore size: 58 Å) were purchased from Sigma-Aldrich and were used as received without further activation.…”

Interpol review of controlled substances 2016–2019

“…Phenyl Acetyl Carbinol (L-PAC and R-PAC): 2016 catalytic asymmetric synthesis of chiral 2-hydroxy ketones using different thiamine diphosphate dependent enzymes including synthesis of (R)and (S)-phenylacetylcarbinol using Lactococcus lactis and Acetobacter pasteurianus [ 380 ]; biotransformation of benzaldehyde into L-PAC using yeast Saccharomyces cerevisiae [ 381 ]; 2017 i mprovement of the yeast based (R)-phenylacetylcarbinol production process via reduction of by-product formation [ 382 ]; improved enzymatic method for the preparation of (R)-phenylacetyl carbinol [ 383 ]; asymmetric synthesis of (S)-phenylacetylcarbinol [ 384 ]; 2018 Biotransformation using halotolerant yeast in seawater to produce R-(−)-phenylacetylcarbinol [ 385 ]; effect of phosphate concentrations at 20, 250, 500, and 1,000 mM on phenylacetylcarbinol production [ 386 ]; Stereoselective synthesis of (1R, 2S)-norephedrine through the biosynthetic of L-phenylacetylcarbinol from benzaldehyde and pyruvate [ 387 ]; synthesis of novel beta-amino alcohols from phenylacetylcarbinol [ 388 ]; ethanol and phenylacetylcarbinol production processes of Candida tropicalis TISTR 5306 and Saccharomyces cerevisiae TISTR 5606 [ 389 ];…”

Cross-acyloin condensation of aldehydes catalysed by transketolase variants for the synthesis of aliphatic α-hydroxyketones

“…The biocatalytic strategies offer not only high chemo–regio- and stereoselectivities but also mild reaction conditions (neutral pH, room temperature, atmospheric pressure and water as solvent). The enzymatic mechanisms of ThDP-dependent enzymes can be a transfer of a ketol or acyl unit from an α-ketoacid to an aldehyde (pyruvate decarboxylase, 9 pyruvate dehydrogenase, 10 transketolase 11 ) or an acyloin-type condensation reaction of two different aldehydes (benzaldehyde lyase, 12 acetoin dehydrogenase, 13 formolase 14 ). This last strategy has the great advantage of adding to previous green criteria, atom economy by avoiding the release of carbon dioxide generated by the decarboxylation of α-ketoacids required by transferases but the best regio- and stereo-selectivities were obtained by cross-acyloin condensation of an aliphatic aldehyde with an aromatic or branched aldehyde.…”