Fluoropyruvic acid

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. ""... 

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. 

Simple unactivated esters do not react with TMSCF3. However, activated esters such as trifluoroacetic acid esters do react. Cyclic esters, i.e. lactones, react with TMSCF3 to give the corresponding adducts. An efficient and simple synthesis of tri-fluoropyruvic acid monohydrate has been developed starting from di-f-butyl oxalate. ... 

N-acetyl-[3-OH]neuraminic acid was synthesized by reaction of N-acetylman-nosamine with bromopyruvate or hydroxypyruvate (DeVries and Binkley 1972). The synthesis of N-acetyl-[3-F]neuraminic acid by condensing fluoropyruvic acid and N-acetylglucosamine or N-acetylmannosamine in alkaline solution has been published by Gantt et al. (1964). 

Bis(trimethylsilyl) ether of 5-triflnoromethyl-6-azauracil 48 was obtained for the synthesis of the corresponding p-D-deoxyribonucleoside and nucleotide. a-Trifluoromethacrylic acid 43 has been converted with hydrogen peroxide to a,p-dihydroxy-a-trifluoromethylpropionic acid 44, which gave the hydrate of per-fluoropyruvic acid 45 on treatment with sodium periodate. The semicarbazone 46... 

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

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... 

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.

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. 

R. J. Mead and W. Segal, Austral. J. Biol. Set., 1972, 25, 327 Fluoroacetic Acid Biosynthesis A Proposed Mechanism . It is suggested that fluoride ion attacks a Cg entity linked to pyridoxal phosphate and derived from cysteine, serine, etc., to yield pyridox-amine phosphate-bound fluoropyruvate (1) which equilibrates with pyridoxal phosphate-bound fluoroalanine (2) subsequent hydrolysis, etc., produces fiuoroacetic acid. 

Based on the ability of the NeuA from E. coli to accept 3-fluoropyruvate 40 as a foreign donor substrate, the synthesis of the two diastereomeric 3-fluorinated siaHc acids 41 and 42 (Scheme 17.16) was reported with an equilibrium ratio of about 4 5, which were sought for as mechanistic probes for kinetic studies as well as for crystal structural determinations of siaHdases and SiaTs [69]. It could be shown that... 

No 3-azido, 3-amino, or Boc-protected mannosamine analogs 12 were accepted by the enzyme (Figure 5.11) [98] which suggests that the presence of a 3-hydroxyl group is a necessary precondition for substrates of the aldolase. Likewise, conformationally inflexible acrylate 13 was not accepted in cleavage direction. By use of fluoropyruvate 15 as the donor substrate a series of dia-stereomeric 3-deoxy-3-fluoro ulosonic acids such as 16 has been prepared in good yields (>49%) from pentoses or hexoses [82]. Such products are attractive for non-invasive in-vivo pharmacokinetic studies by NMR tomography ( F derivatives) or positron-emission spectroscopy ( F derivatives). 

Another interesting example of a redox neutral cascade has been proposed for the multienzymatic synthesis of (JJ)-3-fluorolactic acid together with the resolution of racemic 3-fluoroalanine (Scheme 11.5b) [13]. Optically enriched (S)-3-fluoroalanine (88% ee) was recovered unreacted after the enantioselective oxidative deamination of the racemic substrate catalyzed by the L-alanine dehydrogenase (i-AlaDH) from Bacillus subtilis. This oxidative reaction, which is thermodynamically unfavorable, was driven by the coupled reduction reaction of the intermediate 3-fluoropyruvate catalyzed by rabbit muscle i-lactate dehydrogenase (L-LDH). Since both enzymes are NADH dependent, this coupled... 

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