Chiral intermediates in thiamin catalysis. Stereochemical course of the decarboxylation step in the conversion of pyruvate to acetaldehyde

Abstract

The stereochemical course of the nonenzymic decarboxylation of the adduct of pyruvate and thiamin was determined. Racemic ethyl 2-(lact-2-yl)thiamin was resolved as the 2,3-dibenzoyltartrate salt under slightly acidic conditions. The specific rotations of the free enantiomers of ethyl 2-(lact-2-yl)thiamin are +8.4 f 0.1' and -8.4 f 0.1'. These were converted to the parent acid, 2-(lact-2-yl)thiamin, by acid hydrolysis. The (+) ethyl ester gave the (-) acid ( [ a ] 2 5 D -4.7 f 0.1") while the (-) ethyl ester gave the (+) acid ([a]25D = +4.7 f 0.1'). The acids were allowed to undergo spontaneous decarboxylation under a variety of conditions: aqueous solution, ethanol solution, dimethylformamide solution, and dimethylformamide solution containing brucine. Under all conditions the product was racemic 2 4 I-hydroxyethy1)thiamin. These results require that the reaction proceed via an achiral intermediate or rapidly equilibrating achirally solvated enantiomeric intermediates. Since it is known that enzymic reactions produce a single enantiomer of 2 4 1-hydroxyethyl)thiamin, the stereospecificity of the enzymic reaction is due to the chirality of the protein and not the intrinsic mechanism of the decarboxylation reaction. ( 5 ) Ullrich, J.; Mannschreck, A. Eur. J . Biochem. 1967, 1 , 110. (6) Kiuger, R.; Karimian, K.; Gish, G.; Pangborn, W. A,; DeTitta, G. T. J. Am. Chem. SOC. 1987, 109, 618. The title and caption to Figure 1 contain a typographical error. The enantiomer of HETI shown has a negatiue (but very weak) specific rotation (circular dichroism is preferred for the assignment), as stated in the rest of the paper. This material results from (+)hydroxyethylthiamin and the configuration at the stereocenter is R as indicated. We thank Professor W. Shin for noting the error.

Thiamin diphosphate: a mechanistic update on enzymic and nonenzymic catalysis of decarboxylation

“…Resolution of Lactylthiamin Ethyl lactylthiamin has recently been resolved as the dibenzoyl tartrate salt in acidic solution. 73 The specific rotation of the (+) enantiomer is 8.4°. The separated ethyl esters were converted by hydrolysis to lactylthiamin.…”

Bioorganic Chemistry

“…Continuing brilliant efforts by Kluger's group to elucidate the enzymatic and nonenzymatic mechanism of substrate decarboxylation by thiamine-PP led to the isolation and resolution of racemic 2-(lact-2-yl)thiamin diphosphate as the 2,3-dibenzoyltartrate salt(612,613). The two isomeric…”