Methylmalonic

Interestingly, the allylation of a stabilized carbon nucleophile has been found to be reversible. Complete isomerization of dimethyl methylmalonate, involving bis-allylic C—C bond cleavage, from a secondary carbon 38 to a primary carbon 39 was observed by treatment with a Pd catalyst for 24 h. The C—C bond cleavage of a monoaliylic system proceeds slowly[40]. 

Methylmalonic acid (MMA) in semm is an estabUshed marker of cobalamine deficiency. MMA and other short-chain dicarboxyhc acids react with... 

No appreciable decomposition of the ethoxalyl ester into ethyl methylmalonate takes place when the distillation is carried out at 10 mm. To prevent overheating, the use of an oil bath and a heated column is recommended. 

Three hundred and forty-five grams (1.7 moles) of ethyl ethoxalylpropionate, b.p., ii4-ii6°/io mm. (p. 54), is placed in a round-bottomed flask, of suitable size carrying a reflux condenser, and a thermometer is suspended from the top of the condenser into the liquid. The ethyl ethoxalylpropionate is then heated until a Aigorous evolution of carbon monoxide begins (130-150 ). The temperature of the liquid is gradually raised as the gas evolution diminishes, and finally the liquid is refluxed until no more gas comes off. The ethyl methylmalonate is then distilled. It boils at ig4-iq6 /745 mm., and the yield is 288 g. (97 per cent of the theoretical amount). 

Benzyloxy-2-fluoro-2-methylpropionaIdehyde was prepared in optically active form from (5)-monoethyl 2-fluoro-2-methylmalonate, which had itself been prepared by enzymatic hydrolysis A number of enol silyl ethers or enolates were added to the aldehyde in processes that occur with fair to good diastereoselectivity [6] (equation 6) (Table 2)... 

The structures of 85 and 93 are proved by comparing them with the authentic samples prepared by the following routes. Thus, gramine (86) is converted to diethyl 2-(indol-3-yl)methylmalonate (87, 83%) utilizing our reaction with... 

Reaction of 2-aminopyridine with dimethyl 2-methylmalonate in the presence of some drops of cone. HCl at 150°C for 1 h (96EUP733633), and with diethyl 2-(l-decyl)malonate at 120°C for 5 min (94JCR(S)206) gave 2-hydroxy-3-methyl- and 2-hydroxy-3-(l-decyl)-4//-pyrido[l, 2-n]pyrimidin-4-ones in 2.2% and 7.5% yields, respectively. Reaction of 3-benzyl-2-aminopyridine and diethylmalonate at 190-200 °C for 4 h yielded 9-benzyl-2-hydroxy-4//-pyrido[l, 2-n]pyrimidin-4-one (01MIP9). Cyclocondensation... 

An interesting feature is the sometimes observed pressure dependence of the reaction. The Michael addition of dimethyl methylmalonate 12 to the bicyclic ketone 13 does not occur under atmospheric pressure, but can be achieved at 15 Kbar in 77% yield ... 

Ethyl methyl ketone, 10, 23 17, 74 Ethyl methyl ketoxime, 11, 59 Ethyl methylmalonate, 17, 56 Ethyl i-methylthiol-3-phthaIimidopro-pane-3,3-dicatboxylate, 14, 58 Ethyl nitrite, 10, 22, 25... 

C]7H24N20, 2378-95-2) see Methotrexate diethyl Ai-(5-methylamino-2-thenoyl)-L-glutamate (C15H22N2O5S 112889-02-8) see Raltitrexed diethyl (l-methylbutyl)malonate (C12H22O4 117-47-5) see Secobarbital diethyl methylmalonate... 

The catabolism of leucine, valine, and isoleucine presents many analogies to fatty acid catabolism. Metabolic disorders of branched-chain amino acid catabolism include hypervalinemia, maple syrup urine disease, intermittent branched-chain ketonuria, isovaleric acidemia, and methylmalonic aciduria. 

Unlike the end products of purine catabolism, those of pyrimidine catabolism are highly water-soluble COj, NH3, P-alanine, and P-aminoisobutyrate (Figure 34-9). Excretion of P-aminoisobutyrate increases in leukemia and severe x-ray radiation exposure due to increased destruction of DNA. However, many persons of Chinese or Japanese ancestry routinely excrete P-aminoisobutyrate. Humans probably transaminate P-aminoisobutyrate to methylmalonate semialdehyde, which then forms succinyl-CoA (Figure 19-2). 

Methylmalonic aciduria (Bi2-reslstant) Mucolipidosis II (I-cell disease) Nlemann-Plck disease Sandhoff disease... 

Another interesting example is SHMT. This enzyme catalyzes decarboxylation of a-amino-a-methylmalonate with the aid of pyridoxal-5 -phosphate (PLP). This is an unique enzyme in that it promotes various types of reactions of a-amino acids. It promotes aldol/retro-aldol type reactions and transamination reaction in addition to decarboxylation reaction. Although the types of apparent reactions are different, the common point of these reactions is the formation of a complex with PLP. In addition, the initial step of each reaction is the decomposition of the Schiff base formed between the substrate and pyridoxal coenzyme (Fig. 7-3). 

To obtain a better understanding of the reaction mechanism, some compounds that are considered to he intermediates were subjected to the reaction. Various reaction courses can be considered as illustrated in Fig. 21. Path A a-Methyltropic acid is oxidized to a-phenyl-a-methylmalonic acid. Then, the malonate is converted to optically active a-phenylpropionate hy arylmalonate decarboxylase. In order to confirm this assumption, incubation of the malonic acid with Rhodococcus sp. was carried out. The result obtained was the total recovery of the substrate, indicating that no decarboxylase is present in this bacterium. Path B a-Methyltropic acid is converted to racemic a-phenylpropionic acid, which is deracemized to optically active propionic acid. To examine the possibility of this route, racemic a-phenylpropionic acid was subjected to the reaction to observe... 

An inducible primary amine dehydrogenase in a strain of Mycobacterium convolutum had diverse degradative capability with a broad specificity, and was involved in the degradation of 1- and 2-aminopropane and 1,3-diaminopropane. The products were assimilated by the methylmalonate pathway, or by formation of C2 + Cj fragments (Cerniglia and Perry 1975). 

Both the synthesis of propionate and its metabolism may take place under anaerobic conditions. In Desulfobulbuspropionicum, degradation could plausibly take place by reversal of the steps used for its synthesis from acetate (Stams et al. 1984)—carboxylation of propionate to methylmalonate followed by coenzyme Bi2-mediated rearrangement to succinate, which then enters the tricarboxylic acid cycle. The converse decarboxylation of succinate to propionate has been observed in Propionigenium modestum (Schink and Pfennig 1982),... 

Moller j, Rasmussen K, Christensen L (1999) External quality assessment of methylmalonic acid and total homocystein. Clin Chem 45 1536-1542. 

Sol-gel-derived membranes encapsulating a bis(crown ether) derivative [bis(12-crown-4-ylmethyl) 2-dodecyl-2-methylmalonate] [28] were also fabricated with an initial DEDMS/TEOS ratio of 3 for Na -ISFETs. The Na -ISFETs showed a Nernstian response to Na+ activity changes in the activity range of 1 x 10 " to 1 M and a short response time of 2 s. Employment of a polythiophene interlayer improved the potential instability and the lower detection limit in both of the K - and Na -ISFETs based on the sol-gel-derived membranes with the initial DEDMS/TEOS ratio of 3 (Fig. 8). 

ISFETs based on the sol-gel-derived membranes of (7) and (11), being almost comparable to that for similar ISFETs based on sol-gel-derived membranes simply encapsulating bis[(12-crown-4-)ylmethyl]2-dodecyl-2-methylmalonate [27]. 

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