Malonic acid pathway

Uses. Malonic acid is used instead of the less expensive malonates for the introduction of a CH—COOH group under mild conditions by Knoevenagel condensation and subsequent decarboxylation. The synthesis of 3,4,5-trimethoxycinnaniic acid, the key intermediate for the coronary vasohdator Cinepa2et maleate [50679-07-7] (5) involves such a pathway (13). 

Plant metabolism can be separated into primary pathways that are found in all cells and deal with manipulating a uniform group of basic compounds, and secondary pathways that occur in specialized cells and produce a wide variety of unique compounds. The primary pathways deal with the metabolism of carbohydrates, lipids, proteins, and nucleic acids and act through the many-step reactions of glycolysis, the tricarboxylic acid cycle, the pentose phosphate shunt, and lipid, protein, and nucleic acid biosynthesis. In contrast, the secondary metabolites (e.g., terpenes, alkaloids, phenylpropanoids, lignin, flavonoids, coumarins, and related compounds) are produced by the shikimic, malonic, and mevalonic acid pathways, and the methylerythritol phosphate pathway (Fig. 3.1). This chapter concentrates on the synthesis and metabolism of phenolic compounds and on how the activities of these pathways and the compounds produced affect product quality. 

Precursors of phenylpropanoids are synthesized from two basic pathways the shikimic acid pathway and the malonic pathway (see Fig. 3.1). The shikimic acid pathway produces most plant phenolics, whereas the malonic pathway, which is an important source of phenolics in fungi and bacteria, is less significant in higher plants. The shikimate pathway converts simple carbohydrate precursors into the amino acids phenylalanine and tyrosine. The synthesis of an intermediate in this pathway, shikimic acid, is blocked by the broad-spectrum herbicide glyphosate (i.e., Roundup). Because animals do not possess this synthetic pathway, they have no way to synthesize the three aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), which are therefore essential nutrients in animal diets. 

Che and Kustin studied complexation 438 results for oxalic and malonic acids are in Table 27. From previous relaxation data 07 and their own results, they concluded that the rate constants are more consistent with a normal dissociative pathway if VOL formation from [VO(OH)]+ is assumed. 

The uncatalysed Belousov-Zhabotinsky (B-Z) reaction between malonic acid and acid bromate proceeds by two parallel mechanisms. In one reaction channel the first molecular products are glyoxalic acid and carbon dioxide, whereas in the other channel mesoxalic acid is the first molecular intermediate. The initial reaction for both pathways, for which mechanisms have been suggested, showed first-order dependence on malonic acid and bromate ion.166 The dependence of the maximal rate of the oxidation of hemin with acid bromate has the form v = [hemin]0-8 [Br03 ] [H+]12. Bromate radical, Br02, rather than elemental bromine, is said to play the crucial role. A mechanism has been suggested taking into account the bromate chemistry in B-Z reactions and appropriate steps for hemin. Based on the proposed mechanism, model calculations have been carried out. The results of computation agree with the main experimental features of the reaction.167... 

Fig. 5. Biosynthetic pathways for (I) 6-methylsalicylic acid and (II) the triacetic acid lactone. The structures of the intermediates have not been identified. The stereochemical course of the prochiral carbons (C-2 and C-4 in the triketide intermediate, C-3 and C-5 in 6-MSA) was investigated using R)- and (S)- [l- C,2- H]malonic acid extender substrate analogs in a coupled assay with 6-MSAS and succinyl-CoA transferase. The distinguishable hydrogens originating from the chiral malonyl CoA are labeled with H and H. Triacetic acid lactone synthesis is catalyzed by 6-MSAS in the absence NADPH...

The intermediate of the ElcB mechanism is a carbanion, and thus any factors that stabilise such an ion should favour this mechanism. We have already noted above that on the face of it, elimination reactions are the reverse of addition reactions. However, we also noted that the actual mechanistic pathways involved in elimination reactions were more similar to substitution reactions than addition reactions. This is because normally elimination reactions proceed via a carbonium ion or in a single step that has certain similarities to an SN2 substitution reaction. However, there are also addition reactions that proceed via a carbanion intermediate, for example the Michael-type reaction, in which a carbanion adds to an a,(3-unsaturated carbonyl compound. Indicate the Michael-type addition between the anion formed from the diester of propandioic acid (or malonic acid) and 2-butenal. 

Photochemical decomposition of malonic acid by irradiation in solution has been reported. Some of the radical species produced by this treatment are identical to those formed by the Ce decomposition of malonic acid in the Belousov-Zhabotinsky reaction. The (2 + 2)-cycloadducts (172) can be readily prepared by irradiation of mixtures of the corresponding enone and alkene, and these adducts can conveniently be converted into the hydroperoxide (173) by irradiation at 366 nm in the presence of air and acridine in toluene.The decarboxylation occurs by a free radical pathway and treatment of the hydroperoxide with dimethyl sulfide brings about formation of the ring-expanded ketones or lactones (174),... 

A reaction may be periodic if its network provides for restoration of a reactant or intermediate that has been depleted, while conversion of main reactants to products continues. Periodic behavior often results from competition of two or more contending mechanisms. Predator-prey fluctuations in ecology (Lotka-Volterra mechanisms) provide an easily visualized example. The Belousov-Zhabotinsky reaction—catalyzed oxidation of malonic acid by bromate—involves a similar competition between two pathways. 

Oxoglutarate can also serve as a starter piece for elongation by the oxoacid pathway. Extension by three carbon atoms yields 2-oxosuberate (Eq. 21-1). This dicarboxylate is converted by reactions shown in Eq. 24-39 into biotin and in archaebacteria into the coenzyme 7-mercaptoheptanoylthreonine phosphate (HTP), Eq. 21-1. Lipoic acid is also synthesized from a fatty acid, the eight-carbon octanoate. A fatty acid synthase system that utilizes a mitochondrial ACP may have as its primary fimction the synthesis of ocfanoate for lipoic acid formation. The mechanism of insertion of the two sulfur atoms to form lipoate (Chapter 15) is imcerfain. If requires an iron-sulfur protein jg probably similar to the corresponding process in the synthesis of biotin (Eq. 24-39)9 93a formation of HTP (Eq. 21-1). One component of the archaebacterial cofactor methano-furan (Chapter 15) is a tetracarboxylic acid that is formed from 2-oxoglufarafe by successive condensations with two malonic acid imits as in fatty acid synthesis. ... 

As is true for benzoquinones and anthraquinones, naphthoquinones are derived both by acetate-malonate and by shikimic acid pathways. 

About 150 xanthones have been discovered. Many are po-lyketide derived, although others are formed from combined shikimic acid pathways combined with acetate-malonate units. Three units of malonate react with a hydroxybenzoic acid (Cfi-Ci). Benzophenones may be converted by oxidative ring closure into xanthones (Fig. 10.14) (Weiss and Ed-... 

Degradation of the pyrimidines follows route A of Fig. 211 in most organisms. The final products are carbamic acid, which spontaneously hydrolyses to CO2 and NHg, / -alanine (D 16) and jS-aminoisobutyric acid. In some bacteria, however, a second pathway, route B, exists which yields urea and malonic/methyl-malonic acids as the degradation products. 

Methyl malonic acid (MMA) reduction. Because the bioehemieal pathway that reduees MMA levels in the blood uses only vitamin B12, lowering MMA levels is a test speeific for vitamin B12 activity. Although it is not known for certain, it is likely that this biochemical pathway is an integral part of the function of vitamin B12 in nerve tissue. Thus, if food lowers MMA levels, it can be assumed to provide full vitamin B12 activity. Similarly, the bioavailability of vitamin B12 in lyophilized purple liver was assessed by MMA exeretion to find total vitamin B12 and vitamin B12 analogue eontents in the liver. 

Benzenoid compounds in plants are synthesized by two main pathways the shikimic acid pathway and the acetate-malonate pathway. In higher plants, a large number of aromatic compounds are derived from phenylalanine, tyrosine, and tryptophan, end-products of the shikimic acid pathway. 

Malonic acid serves as a ketene precursor in solid phase N-acetylation of peptides catalyzed by diisopropylethylamine by reaction with the catalyst HBTU (O-benzotriazole-iV, N, N, JV -tetramethyluronium hexafluoro-phosphate) in dg-DMF forming a malonate/tetramethylurea complex that gives ketene and tetramethylurea, as shown by anisidine acetylation (Scheme 4.7). Computational methods favored the pathway shown for ketene generation. This method was used in the acetylation of a variety of resin bound peptides. 

Boron-Oxygen Compounds. Work on the kinetics of complexation between phenyl-boronic acid and oxalic acid or malonic acid shows the existence of parallel pathways involving conjugate acid-base species of the ligand. Studies have also been published on the kinetics of complex formation between boric acid and benzoyl-acetone or a substituted benzophenone. ... 

The decomposition pathways of DBNPA described by Exner et al. (1973) are shown in Figure 21. Hydrolysis ends with oxalic acid which oxidizes slowly to CO2. The reaction of DBNPA with nucleophiles leads to malonic acid, which is just as oxalic acid a naturally occurring dicarboxylic acid it may further degrade to acetic acid and CO2. 

As may well be apparent periodicity in chemical systems requires coupled, competing processes. Without coupling via bromide ion the Belousov-Zhabotinskii reaction would just provide parallel pathways for the consumption of bromate ion and malonic acid. The coupling compels feedback which creates the possibility of switching from one path to the other. Since the time scale of the processes is comparable switching and oscillation are observable. In a similar way thermochemical and electrochemical oscillators may be designed. Furthermore spatial, rather than temporal, periodicity may be observed. We consider a few examples. 

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