Methyl group transfer

FIGURE 18.29 Vitamin B19 functions as a coenzyme in intramolecular rearrangements, reduction of ribonucleotides, and methyl group transfers. 

The first two of these are mediated by 5 -deoxyadenosylcobalamin, whereas methyl transfers are effected by methylcobalamin. The mechanism of ribonucleotide reductase is discussed in Chapter 27. Methyl group transfers that employ tetrahydrofolate as a coenzyme are described later in this chapter. 

Methyl-tetrahydro folic acid is furthermore, together with vitamin B12 and B6, required to regenerate homocysteine (see Vitamin B12, Fig. 1). Homocysteine results when methionine is used as a substrate for methyl group transfer. During the last few years, homocysteine has been acknowledged as an independent risk factor in atherosclerosis etiology. Folic acid supplementation can help reduce elevated homocysteine plasma levels and is therefore supposed to reduce the risk of atherosclerosis as well [2]. 

Methyl Group Transfer from Methyl-Co to Cluster A... 

The corrinoids involved in methyl group transfer do not possess the organo-ligand 5 -deoxyadenosyl [see structure (II), Section I,B] and the reaction probably proceeds via the intermediate formation of the methyl cobalt complex, but no mechanistic details have yet been established. 

A new, heat-stable, coenzyme concerned with methyl group transfer has been isolated from Methanobacterium. The coenzyme, which is involved in transmethylation reactions prior to methane formation by the organism, contains phosphorus and has a u.v. absorption at 260 nm, suggesting that it may be a nucleotide. 

In contrast with the role of cofactor B12 in methionine synthase (methyl group transfer to a thiol), functional Bi2 model complexes have provided a formidable challenge. Several oxime alkyl-cobalt (structural) B12 models when reacted with arene- and alkanethiolates lead only to... 

Cyclohexadienylidenes, disubstituted at the 4-position are expected to be kinetically more stable than the parent carbene, however, the rearrangement to benzene derivatives is still very exothermic. The gas phase chemistry of 4,4-dimethyl-2,5-cyclohexadienylidene Is was investigated by Jones et al.100,101 The gas phase pyrolysis of the diazo compound 2s produces a mixture of p-xylene and toluene, and by crossover experiments it was demonstrated that the methyl group transfer occurs intermolecularly via free radicals. Thus, the pyrolysis of a mixture of the dimethyl and the diethyl derivative 2s and 2t... 

The functions of folic acid and vitamin B12 are very closely linked, especially in what is known as one carbon metabolism or methyl group transfer. 

The anaemia in B deficiency is caused by an inability to produce sufficient of the methylating agent S-adenosyhnethionine. This is required by proliferating cells for methyl group transfer, needed for synthesis of the deoxythymidine nucleotide for DNA synthesis (see below and Chapter 20). This leads to failure of the development of the nucleus in the precursor cells for erythrocytes. The neuropathy, which affects peripheral nerves as well as those in the brain, is probably due to lack of methionine for methyl transfer to form choline from ethanolamine, which is required for synthesis of phosphoglycerides and sphingomyelin which are required for formation of myelin and cell membranes. Hence, the neuropathy results from a... 

The compounds that are the immediate methyl gronp donors are methyltetra hydrofate (CH3-FH4) and S-adenosyl methionine (SAM) (see Figure 15.2). These are involved in, at least, five key reactions or processes which are summarised in Figure 15.4. Complexity arises in the topic of methyl group transfer in formation and reformation of the methylating compounds 5-adenosylmethione and methyl tetrahydrofolate. There are four important reactions in the formation utilisation and then the reformation of 5-adenosylmethionine as follows ... 

When the distannyl reagent 7 is employed, the fate of the reaction apparently depends on the reaction conditions. Indeed, Eisch observed that the reaction of 7 with boron trichloride at —40 °C in hydrocarbon solvent is not always selective and leads to the formation of both a monoborylated intermediate (10) that slowly converts into 6 (Scheme 5). The outcome of these reactions is apparently further complicated by a fast methyl group transfer from the tin to the boron centers yielding the undesired monoborylated derivative 11. Eisch also found that such reactions are not limited to the case of boron trialide but can be performed with dialkyl boron halide starting materials. For example, the reaction of the distannane... 

CP/MAS NMR study of CH4 activation on [(=SiO)2Ta(H)J shows the formation even at 150 °C of methyUdene and methyUdyne species by an a-H elimination process on several sites that should correspond to the tris-hydride on other sites a methyl group is transferred to the surface, leading to the formation of (=Si-Me) and of [(=SiO)3Ta]. Correlation with EXAFS suggests that the tris-hydride should exist on surface sites (=20%) quite distant from siloxy bridges whereas methyl transfer to the surface should happen on the specific sites (=80%) close to the siloxy bridges. The latter, which are formally 10 electrons species, exhibit a moderate to weak activity in methane C-H activation. To the best of our knowledge, this is the first observation of methyl group transfer on a surface (Scheme 2.18). 

Scheme 7 A proposed mechanism for a living polymerization involving rapid methyl group transfer.

Although tetrahydrofolate can carry a methyl group at N-5, the transfer potential of this methyl group is insufficient for most biosynthetic reactions. S -Adenosyl-methionine (adoMet) is the preferred cofactor for biological methyl group transfers. It is synthesized from ATP and methionine by the action of methionine... 

The exact role of the nickel of F430 in methane formation is not clear at present. Analogy with the cobalamins, and the observation of an EPR-detectable reduced state, might suggest that it is involved in either methyl group transfer, reduction, or both. 

A methyl group, which displays electron-donor properties (+/, +M), facilitates the acid-catalyzed and hinders the alkali-catalyzed exchange, in deuteriated methylselenophenes. The partial rate factors (/) show that a methyl group transfers its electronic effect in selenophene79 almost as effectively as in thiophene.86... 

From the mechanism sketched in Scheme 1 one can conclude that carbomagnesation is unsuitable for a methyl group transfer. Homologous Grignard reagents, as seen in the transformation 19 to 20, however, can be used successfully in some cases. This example directs attention to a further aspect of this chemistry, i.e. the high stereoselectivity of many Zr-catalyzed carbomag-nesations. 

TMP and 2,3,4-TMP in TMP distribution at 60°c (Figure 2) could be due to increased degree of self-alkylation and butene dimerization, followed by rapid hydride and methyl group transfers. Based on the extrapolations from these two figures, the RON of C5+ alkylate at -40°C was calculated to be 102.7. The RON... 

The degenerate methyl group transfer in [5] has also been observed by Stahl et al. (1978) in electron-impact studies of C-labelled heptyl iodides. n-Heptyl and branched iodides all give ions that isomerize to [5] prior to fragmentation. 

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