3-fluoropyruvate

One of the syntheses of f1 udalanine begins with base promoted condensation of ethyl fluoroacetate and ethyl oxalate to give This is then converted by hydrolytic processes to the insoluble hydrated lithium salt of fluoropyruvate (58). This last is reductively aminated by reduction with sodium boro-deuteride and the resulting racemate is resolved to give D-flu-dalanine (59). 

Extensive studies have indicated that only pyruvate is acceptable as the NeuA donor substrate, with the exception of fluoropyruvate [49], but that the enzyme displays a fairly broad tolerance for stereochemically related aldehyde substrates as acceptor alternatives, such as a number of sugars and their derivatives larger or equal to pentoses [36,48,50,51]. Permissible variations include replacement of the natural D-manno configured substrate (4) with derivatives containing modifications such as epimerization, substitution, or deletion at positions C-2, -4, or -6 [16,27]. Epimeriza-tion at C-2, however, is restricted to small polar substituents owing to strongly... 

Synthetic fluoropyruvate,5 FCH2COCOONa is much less toxic than fluoroacetic acid and surprisingly does not affect the tricarboxylic acid cycle. 

Enantiopure (5)-fluoroalanine has been prepared by an enzymatic path starting from 3-fluoropyruvate in the presence of alanine dehydrogenase, and also by chemical synthesis from (5)-p-tolyl methyl sulfoxide (Figure 5.1) or from the L-serine. The analogue labeled with F has been prepared for use in positron emission tomography (PET) used in cancer diagnosis. ... 

Fluoropyruvate is converted quantitatively by pyruvate decarboxylase from wheat germ into acetate, fluoride (F ), and carbon dioxide. Propose a reaction mechanism. See Gish, G., Smyth, T., and Kluger, R. (1988) /. Am. Chem. Soc. 110, 6230-6234. 

A novel variation of the method of adding an allylie alcohol to a reactive a-fluoro carbonyl compound, as shown in the previous example, has been developed by Shi and Cai in a general strategy for the synthesis of /h/i-difluoro-a-amtno acids via the a-oxo esters 53.20 Ethyl tri-fluoropyruvate reacts with primary allylie alcohols 49 in benzene to form the stable hemiacetals... 

Fluoropyruvate inhibits an enzyme which is located on a bypass of lysine metabolism, with the result that more carbon flows towards lysine. The yield was increased to 50 g L 1. 

When cucurbit cells are fed O-acetylserine or its metabolic precursors the rate of hydrogen sulfide emission in response to sulfate declines, and the incorporation of labeled sulfur from 35S-sulfate into cysteine increases (18). Inhibition of the synthesis of the O-acetylserine precursor acetyl coenzyme A by 3-fluoropyruvate (22) enhances hydrogen sulfide emission, but inhibits cysteine synthesis (1 ). These observations indicate that the availability of O-acetylserine is the rate limiting factor in cysteine synthesis. Hydrogen sulfide may be emitted to the extent the amount of sulfate reduced exceeds the synthesis of O-acetylserine. Therefore, direct release of sulfide from carrier-bound sulfide appears to be responsible for the emission of hydrogen sulfide in response to sulfate (Figure 1, pathway 1). 

Both Hiibner85 and Kluger s group86 reported that fluoropyruvate was a substrate for PDC, that also eliminated fluoride ion producing acetate, without inactivating the enzyme. 

Activated esters, such as oxalates, are also reactive towards trimethyl(perfluoroalkyl)silanes under fluoride catalysis as reported in the case of di-/cr/-butyl oxalate which affords tri-fluoropyruvic acid 26 (Rp = CFj) in hydrated fonn. ""... 

R, = OH, Rj = H, R2 = OH, R4 = CHjOH in Table 3), the enantiomeric compound of the one just reported could be easily prepared. Aldol condensation products were obtained as diastereomeric mixtures from L-sugars, such as L-fucose, L-xylose, L-lyxose, and o-sugars epimeric to o-mannose relative to the 3-position, such as D-allose and o-gulose [46-48]. Table 4 lists the corresponding aldol condensation products isolated as diastereomeric mixtures. Also, 3-deoxy-D-mannose by condensation with pyruvate gave a diastereomeric mixture of 6-deoxy-KDN furanose derivatives [43]. All these results confirm that sialic acid aldolase, similar to other aldolases, exhibits broad specificity toward the electrophilic acceptor on the other hand, only pyruvate was reported acceptable as the donor [10]. But very recently, in contradiction to that, 3-fluoro-Neu5Ac and 3-fluoro-KDN could be prepared by the sialic acid aldolase-catalyzed condensation of 3-fluoropyruvate and Af-acetylmannosamine or o-mannose (Scheme 5) [47]. 

Scheme 5 Aldol addition of fluoropyruvate with A-acetylmannosamine or mannose catalyzed by sialic acid aldolase.

T. MR spectra of sodium fluoropyruvate in D2O are given belowr. Are these data, j ible with ttie structure shown If not, suggest how the compound might exist in this... 

To elucidate the mechanism in flavocytochrome 62, a series of reactions similar to those mentioned above were carried out. Urban et al. Ill) studied the reverse reaction in flavocytochrome 62 and demonstrated that dehydrohalogenation did indeed occur with bromo- and chloropyruvate, but not with fluoropyruvate. A partition ratio of 500 was found for oxidation versus elimination during the forward reaction (i.e., 1 mol of pyruvate formed for every 500 mol of halopyruvate) compared with a partition ratio of 2 for the reverse reaction 111). 

It was reported that -fluoropyruvate is an effective inhibitor of PDHc that eliminated fluoride ion in an enzyme concentration-dependent manner. Presumably, this resulted from initial formation of the enamine from decarboxylation, followed by elimination of fluoride leading to 2-(l-hydroxyethenyl)ThDP, that on ketonization gave... 

It is also noteworthy that, in the presence of ThDP and pyruvate only, some PDHcs have been reported to undergo slow inactivation . This inactivation could be explained using a combination of now known facts. If on decarboxylation of pyruvate the enamine undergoes slow air-oxidation concomitant with turnover, the resulting 2-acetylThDP can periodically transfer its acetyl group to a CysSH on the enzyme, rather than to water. This would lead to inactivation, according to the model for fluoropyruvate-induced inactivation discussed in equation 9. 

Sialic acid aldolase catalyzes the condensation of pyruvate and N-acetylmannosamine to form sialic acid, an acidic sugar involved in a number of biochemical recognition processes. Like other aldolases, sialic acid aldolase accepts a number of aldoses as substrates (12,13). Mannose, 2-deoxyglucose, and many 6-substituted or 6-modified mannose or N-acetylmannosamine, for example, are good substrates for the enzyme. We have prepared 9-deoxy-9-fluorosialic acid and a 7,9-difluoroderivative of sialic acid using sialic acid aldolase as catalyst (Figure 4). In an attempt to prepare 3-deoxy-3-fluorosialic acid, it was found that 3-fluoropyruvate is not a substrate for the enzyme. 

A-Acetyl-3-fluoroneuraminic acid (3-fluorosialic acid) has been synthesized in low yield by the condensation of fluoropyruvic acid with 2-acet-amido-2-deoxy-D-glucose or 2-acetamido-2-deoxy-D-mannose at pH 11. 

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