Formaldehyde activated

A subclass of lyases, involved in amino acid metabolism, utilizes pyridoxal 5-phosphate (PLP, 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarbaldehyde) as a cofactor for imine/ enamine-type activation. These enzymes are not only an alternative to standard fermentation technology, but also offer a potential entry to nonnatural amino acids. Serine hydroxymethyl-tansferase (SHMT EC 2.1.2.1.) combines glycine as the donor with (tetrahydrofolate activated) formaldehyde to L-serine in an economic yield40, but will also accept a range of other aldehydes to provide /i-hydroxy-a-amino acids with a high degree of both absolute and relative stereochemical control in favor of the L-erythro isomers41. 

Treatment of the optically active formaldehyde dithioacetal monoxide with ethyl benzoate in the presence of sodium hydride gives the benzoylated product as a diastereomeric mixture in a thermodynamically controlled (65 35) ratio66. 

The results indicate that in homogenous medium it is not possible to reach high guaiacol conversion. Under the conditions which are necessary to activate formaldehyde, the condensation reaction between vanillols or between p-vanillol and guaiacol is very quick. This is likely due to the high stability of the benzyl carbocation which forms by protonation of the hydroxymethyl group on p-vanillol [8],... 

A number of pseudomonads and other bacteria convert C compounds to acetate via tetrahydrofolic acid-bound intermediates and C02 using the serine pathway179 192 193 shown in Fig. 17-15. This is a cyclic process for converting one molecule of formaldehyde (bound to tetrahydrofolate) plus one of C02 into acetate. The regenerating substrate is glyoxylate. Before condensation with the "active formaldehyde" of meth-... 

The pyridoxal-5 -phosphate dependent serine hydroxymethyltransferase (SHMT EC 2.1.2.1) in vivo catalyzes the interconversion of L-serine 158 and glycine 149 by transfer of the /1-carbon of L-serine to tetrahydrofolate (THF) by which the activated formaldehyde is physiologically made available as a C,-pool. The reaction is fully reversible and provides a means for the stereoselective synthesis of 158 in vitro from donor 149 and formaldehyde. Economical yields (88-94%) of L-serine have thus been obtained on a multimolar scale using raw cell extracts of recombinant Klebsiella aerogenes or E. coll in a controlled bioreactor at final product concentrations > 450 gl 1 [461,462], Several SHMTs have been purified and characterized from various organisms including animal tissues [463,464], eucaryotic [465] and procaryotic... 

The first step is a carbonyl ene reaction, also known in the literature as a Prins reaction.7 A Lewis acid activates formaldehyde (25) for attack on the double bond of 12. This results in zwitterionic intermediate 26, which leads to the ene product 27 in the form of a dimethylaluminum complex through 1,5-migration of a proton. This complex is unstable and spontaneously eliminates methane. Aqueous workup hydrolyzes aluminum alkoxide 28 to alcohol 24. 

The decarboxylation of glyoxalate results in the formation of active formaldehyde . Since the release of formaldehyde is very slow, glyoxalate is a uncompetitive inhibitor of PDC [128,160],... 

The mixture of formamide and formaldehyde is also responsible for the formation of adenine and purine acyclonucleosides 32-34, probably by a formose-like condensation of an activated formaldehyde on the exocyclic formyl moiety of formylpurine and adenine derivatives 28-29. Nucleosides... 

H foiate, as shown in Figure 9.13, The lorbon unit bound to 5,10-methylene-H4 folate was at one time called "active formaldehyde." The FAD cofactor is covalently bound to dimethyl- and monoitiethylglycine dehydrogenases. Trimethyl-giycine is also called betaine. Monomethylglycine is also called saicosine. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for long-term federal cleanup activities. Formaldehyde has been found in at least 26 of the 1,428 current or former NPL sites. However, it s unknown how many NPL sites have been evaluated for this substance. As more sites are evaluated, the sites with formaldehyde may increase. This is important because exposure to this substance may harm you and because these sites may be sources of exposure. 

C H23N70s, Mr 445.43, [a] +14.9° (0.1 M NaOH). A coenzyme, unstable in solution and in the air, that transfers a one-carbon unit in metabolic processes (C, activated formaldehyde, activated formic acid ) (see... 

It is proposed that this reaction involves an acid-activated formaldehyde intermediate (i.e., in the form of hydroxymethyl carbonium ion ) that electrophilically attacks the olefinic double bond to form an oxetane oxonium or a three-member bridged... 

It catalyses the aminolysis of epoxides in an extraordinarily efficient manner in aprotic solvents (e.g. toluene, CH2CI2) with complete trans stereoselectivity and high regioselectivity [Chini et al. Tetrahedron Lett 35 433 1994], It also catalyses the trans addition of indole (at position 3) to epoxides (e.g. to phenoxymetltyloxirane) in >50% yields at 60° (42 hours) under pressure (10 Kbar) and was successfully applied for an enantioselective synthesis of (+)-diolmycin A2 [Kotsuki Tetrahedron Lett 37 3727 799(5]. Of the ten lanthanide triflates, Yb(OTf)3 gave the highest yields (> 90%, see above) of condensation products by catalytically activating formaldehyde, and a variety of aldehydes, in hydroformylations and aldol reactions, respectively, with trimethylsilyl enol-ethers in THF at room temperature. All the lanthanide triflates can be recovered from these reactions for re-use. [Kobayashi Hachiya J Org Chem 59 3590 1994.]... 

Active formaldehyde see Active one-carbon units. Thiamin pyrophosphate. 

Methylenetetrahydrofolate can be transformed to the other cosubstrates by the reactions given in Fig. 23. On hydrolysis of 5,10-methylenetetrahydro-folate formaldehyde is formed. It may be called therefore activated formaldehyde . Formic acid and methanol are formed from the other cosubstrates (Table 16). It is unknown, however, whether the formic acid released as an alarm phermone by certain ants (E 4), or formic acid and methanol in some plants are synthesized in this way. 

The formation of an unknown intermediate at the level of oxidation of formaldehyde in the chemical scheme from glyoxylic acid to formic acid to CO2, is based upon observations that an activated formaldehyde-like 1-carbon unit is concerned in the formation of the /3-carbon of serine. ... 

Nonenzymatically, HCHO reacts readily with FH4 at neutral pH and at room temperature to form one or more products active in systems requiring hydroxymethyl-FH4 this does not tell whether active formaldehyde is attached at iV, N, N, or A . In the glycine serine system, HCHO must be activated enzymatically for the reaction to proceed (Osborn and Huennekens, 1957 Osborn et al., 1958b). 

As discussed by several reviewers (notably, Huennekens et al., 1958 Coon and Robinson, 1958), folic coenzymes at the hydroxymethyl- and formyl oxidation states are almost certainly interconverted by way of 1V -FH4 bridge compounds. Kisliuk (1957) proposed an attachment of active formaldehyde to the methylene carbon in the glycine - serine conversion... 

Hydroxypyruvate can be formed from serine by transamination dihy-droxyacetone is readily phosphorylated to triose phosphate. As CO is removed, more hydroxypyruvate could be formed from serine. Some such cycle would provide a nonfolic-mediated disposition of formaldehyde. Formaldehyde, in turn, could be generated by the oxidation of the W-methyl of sarcosine sarcosine in turn is generated by the removal as active formaldehyde of one of the methyls of dimethylglycine (Mackenzie and Frisell, 1968). Dimethylglycine is formed by the well-established sequence sarcosine — glycine + HCHO serine ethanolamine + COj — mono-methylethanolamine —> dimethylethanolamine —> choline —> betaine —> dimethylglycine. 

Pathway 1 is by the condensation of active formaldehyde and glycine to form serine. The latter can be hydrolytically deaminated to P3rruvic acid. Pathway 2 is by transamination to glyoxylic acid and the oxidation of this... 

Enzymically reactive formaldehyde is formed by its combination with FH4 the particular structure of the active formaldehyde, however, is still in some doubt. FH4 probably is not tire true form of this coenzyme in nature. Rabinowitz and EQmes (4 a) have isolated a diglutamyl-FH4 from Clostridium cylindroaporum and Wright (47) has secured evidence of a more complex form of this eoenzyme than FH4. 

Posable structures for active formaldehyde are N -CHtOH-FH4, N -CH/)H-FH4, or N -CH FH4. In fact, as st ested by Blakley (4 ), there may be an equilibrium between all of these forms. It is conceivable that there are several different active formaldehyde coenzymes, special ones being required for the different reactions entered into by the formaldehyde. 

Briefly, the evidence in support of the several postulated structures of active formaldehyde is as follows in favor of the N - structure is the observation that C Mormaldehyde does not combine with N -substituted pteri-dine compounds (48) the N - position, according to Blakley (48), need not... 

Enzymic evidence favorable to the methylene bridge structure is the observation that only the corresponding N - -CH-FH4 serves as a substrate for purified CHsOH-FH4 dehydrogenase 51). In confirmation of this it has been observed that the N - -CH-FH4 formyl compound, but neither the N - nor N -CHO-FH can be reduced with borohydride to yield active formaldehyde 44)-... 

Formaldehyde reacts spontaneously with FH4 to form active formaldehyde 35, 62). Since there is a multiplicity of potential binding sites for the latter in FH4, formation of a mixture of compounds might well be expected. Contrary to this is the finding of Blakley 60) that only 1 mole of formaldehyde is bound per mole of FH4. 

The authenticity of the enzymically formed active formaldehyde was established by its reactivity in serine biosynthesis and its oxidation to... 

Folic acid (Fig. 6) is the precursor of a number of coenzymes vital for the synthesis of many important molecules. These derivatives of folic acid, referred to collectively as active formate and active formaldehyde , are responsible for the donation of one carbon fragments in the enzymatic synthesis of a number of essential molecules. In the formation of methionine from homocysteine, the folic acid coenzyme donates the S-methyl group, and in the conversion of glycine to serine it is necessary for the formation of the hydroxymethyl group. Folic add is converted into its active coenzyme forms by an initial two step reduction to tetra-hydrofolic add (Fig. 6) by means of two enzymes, folic reductase and dihydrofolic reductase. Conversion of tetrahydrofolic acid (THF) to an active coenzyme folinic acid subsequently occurs by ad tion of an Ns formyl group (Fig. 6). The formation of similar compounds such as an Nio formyl derivative, or the bridged Ns,Nio-methylenetetrahydrofolic acid, also leads to active coenzymes. 

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