ABSTRACT
Racemic ethyl hydrogen (1-hydroxy-2-methylsulfanyl-1-phenylethyl)phosphonate was resolved with (R)-1-phenylethylamine. The (R)-configuration of the (-)-enantiomer was determined by chemical correlation. Esterification of the (-)-enantiomer with a substituted diazomethane derived from 3-hydroxy-1,3,5(10)-estratrien-17-one delivered two epimeric phosphonates separated by HPLC. Methylation with methyl fluorosulfate at the sulfur atom and treatment with a strong base induced an α-hydroxyphosphonate-phosphate rearrangement with formation of dimethyl sulphide and two enantiomerically pure enol phosphates. Their oily nature interfered with a single crystal X-ray structure analysis to determine the stereochemistry at the phosphorus atom.
ABSTRACT
Enzymes and chirality are intimately associated. For their mechanisms to be studied, chiral substrates are needed as probes. Here, we report a concise synthesis of (RP)- and (SP)-[16O,17O,18O]phosphoenol pyruvate starting from enantiomerically pure (R)-2-chloro-1-phenylethanol, which was transformed into 18O-labeled 3-methyl-1-phenylbutane-1,3-diol. The diol was reacted with tris(dimethylamino)phosphane and consecutively with H217O to yield a mixture of cyclic H-phosphonates labeled with 17O and 18O. They were silylated and subjected to a Perkow reaction with ethyl 3-chloropyruvate. Two protected-[16O,17O,18O]phosphoenol pyruvates were formed and finally globally deprotected. Their configuration was reassessed by a known enzymatic test in combination with conversion of the formed d-glucose-6-phosphate into mixtures of labeled methyl d-glucose-4,6-phosphates, which were analyzed by 31P NMR spectroscopy. The enzymatic test supported the configuration assigned to labeled stereogenic phosphorus atoms on the basis of synthesis.
