Synthesis of stereospecifically deuterated fluoroacetic acid and its behaviour in enzymic aldol‐type condensations

Structure of the Escherichia coli malate synthase G:pyruvate:acetyl‐coenzyme A abortive ternary complex at 1.95 Å resolution

“…Fluoroacetyl‐CoA is a substrate for both citrate and malate synthase. In the latter case, (2R, 3R) and (2R, 3S) 3‐fluoromalate are produced in a 3:4 ratio (Keck et al 1980; Marletta et al 1981). This implies that malate synthase does not strongly distinguish between the pro‐R and pro‐S hydrogens in the rate‐limiting step.…”

Some influences of fluorine in bioorganic chemistry

“…70,71 Thus in this case the enzyme does not control the stereochemistry of the new chiral centre generated as a consequence of fluorine substitution. These aldol reactions must proceed via enzyme bound enol or enolate intermediates of fluoroacetyl-CoA, and clearly these enols can have Z or E geometries.…”

Fluorinated Substrate Analogs: Routes of Metabolism and Selective Toxicity

“…It has been claimed that with racemic 3R,3S-fluorooxalacetate, only one diastereomer of 2-fluorocitrate, now a nontoxic isomer, is produced. More recent NMR studies of Keck and Retey, though, show conclusively that both 2R,3R-and 2S,3R-2-fluorocitrates are formed (24). The enzyme does not distinguish among the two isomers of 3-fluorooxalacetate.…”

“…A limitation of the chiral methyl methodology is the fact that in conversion of, for example, R-C-[' H,2H,3H]acetate to a population of 2-['H,3H]-and 2-[2H,3H]-citrates, physical separation of the minority fraction of tritium-containing molecules (only those are chiral, or course, and assayable for radioactivity) is not possible. One must synthesize chiral C-['H?H]F groups, as has been done only for fluoroacetate to date (24). Even then CHzF centers may react at much reduced rates due to the electronegativity effect of the fluorine.…”