Enzymatic synthesis of chiral organophosphothioates from prochiral precursors.
The phosphotriesterase from Pseudomonas diminuta has been shown to selectively cleave the pro-R p-nitrophenolate substituent from bis-p-nitrophenyl alkyl phosphothioate esters. When the alkyl substituent is methyl, ethyl, or isopropyl the enantiomeric excess of the product is >/=99%. Manipulation of the active site through mutagenesis has enabled the preparation of protein variants that preferentially hydrolyze the pro-S substituent of the target substrates. This methodology thus permits the preparation of chiral products from prochiral precursors.
Li
Wen-Shan
WS
Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, USA.
Li
Yingchun
Y
Hill
Craig M
CM
Lum
Karin T
KT
Raushel
Frank M
FM
D043303:Aryldialkylphosphatase; D018360:Crystallography, X-Ray; D004950:Esterases / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D009946:Organothiophosphorus Compounds; D004950:Esterases; D043303:Aryldialkylphosphatase