The Dicarboxylic Acid System

Metabolic Sources and Mutual Rdaiions of the Amino Dicarboxylic Acids 

Free AS and GL and glutamine are regular constituents of the nonprotein nitrogen fraction of tissues and blood they account for to H of the a-amino-N of this fraction. Large amounts of GL and AS are continuously liberated by the enzymatic hydrolysis of tissue and food proteins, which frequently contain as much as 25% dicarbo lic amino acids, or more. Many other amino acids are transformed into components of the dicarboxylic acid system by special metabolic reactions. 

In Fig. 2 a scheme is ven for the genetic interrelationB of amino acids, converging toward components of the dicarboxylic acid system. The scheme includes all amino acids with the exception of valine, leucine and isoleucine, capable of slow transamination, and of glycine and tryptophan, which are catabolized by independent pathways. 

Underlined —amino acide forming part of the protune in braekete—derivativeB and amino acids not contained in the prateme dotted arrows — probable, but not proved transformationBj in parentheses along the arrows are indicated the parta of amino aeid molecules involved in the reqieetive transformations. 

Role of AccejOor and Donator Functions of the DidxrboxyUe Adds tn Metabolic Coordination 

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Tbiamine, aneurin or vitamin Bj is directly concerned with intermediate carbohydrate metabolism, and the extensive work of R. Peters has shown that in the form of its diphosphoric ester (co-carboxylase), it works in conjunction with the dicarboxylic acid system of Szent-Gy5rgyi in brii ing about the characteristic oxidation of pyruvate in brain tissue. 

A thin-layer gas chromatographic system was devised by Pittman and Shekosky(39) for chicken tissue and feces. A TLC system of benzene methanol acetic acid (9 1 1) was used for prior separation the spots were then removed and esterified in 14% BF in methanol. A 4 ft. 3% OV-17 column at 240° was used. Retention times of about 7 minutes for nalidixic acid, 10 minutes for hydroxynalidixic acid and 17 minutes for the dicarboxylic acid were reported. 

A pulse polarographic system for detection of the dicarboxylic acid in the presence of nalidixic and hydroxynalidixic acids was devised by Koss and Warner.(45) The reduction potential in the system used was -.54V vs. SCE. 

The gel-prevention action in the water-poor part of the system is Illustrated by a comparison between the dicarboxylic acid and a monocarboxylic acid of approximately the same carboxylic/methylene group ratio. 

These results showed an important feature of the dicarboxylic acid in question. Contrary to the corresponding monocarboxyllc acid, it prevents the formation of a liquid crystalline phase in water-poor systems. The implications of this fact for the formulations of liquid cleaners is obvious. 

The results are straight forward and the interpretation immediately evident. The liquid crystalline phase formed in these extremely water rich systems was destabilized by the dicarboxylic acid and transformed to an isotropic solution. The conclusion that the hydrotropic action of the dicarboxylic acid is intimately related to its capacity to destabilize a liquid crystalline phase also under the water-rich conditions during actual laundering conditions appears well justified. 

Metal-catalyzed allylic substitution reactions have been a mainstay of synthetic chemistry because of their ability to proceed irreversibly and with high selectivity [42]. It is also feasible, however, to produce analogous systems that are completely reversible and nonselective, or ideally situated for use in DCC. These are essentially metal-catalyzed transesterification reactions, with the added feature of potentially providing stereochemical scrambling (and selection) as well as constitutional variation. An early example of this was provided in 2000 by Kaiser and Sanders [43]. In the absence of a template, reaction of diallyl diacetate 22 with a dicarboxylic acid in the presence of catalytic Pd(0) produced a negligible amount of the cycfized compound 23 (Fig. 1.9). However, when templated with 1,3-bis(4-pyridyl) benzene, yield of the cyclic structure increased to roughly 10%, independent of the dicarboxylic acid used. 

There are two principal synthetic routes to dicarboxylate complexes. One of these uses an aqueous solution of the alkali metal dicarboxylate and the corresponding metal halide,93 while the other depends upon the dicarboxylic acid reduction of higher oxidation state metals. This reductive property of oxalic acid results in its ready dissolution of iron oxides and hence a cleaning utility in nuclear power plants.94 Mention must also be made of the successful ligand exchange synthesis of molybdenum dicarboxylates, Mo(dicarboxylate)2 H2 O, from the corresponding acetate complex. Unfortunately the polymeric, amorphous and insoluble nature of these complexes has restricted the study of these systems, which may well provide examples of multiple M—M bonding in dicarboxylate coordination chemistry.95... 

Alkaline pyrophosphatase dependent on Mg2+ was found in every sample examined from a broad spectrum of the plant kingdom (SI). Plants which fix C02 by the dicarboxylic acid pathway have characteristic high levels of alkaline pyrophosphatase in their chloroplasts presumably this performs the rather specific function of driving the synthesis of phosphoenolpyruvate, the immediate precursor of C02 fixation (32). Biosynthesis of the maize chloroplast enzyme is controlled by light acting through the phytochrome system (S3). Pyrophosphatase from spinach chloroplasts has been partially purified (34, 35). 

A total synthesis of ( )-royleanone from 5,7,8-trimethoxy-l-tetralone (123) has been described.129 The tetralone was converted into the tricyclic ketone (124), which was in turn converted into 11,12,14-trimethoxypodocarpatriene (125). Demethyla-tion and oxidation afforded the quinone (126 R = H) which was alkylated to give royleanone (126 R = Pr ). Synthetic studies in the resin acid series have led130 to the preparation of the dicarboxylic acid (127) with a cis a/b ring junction. The preparation of some tetracyclic ketones as intermediates for gibberellin synthesis has been described.131 132 The key reaction involves photolysis of a diazoketone (128) to afford the tetracyclic system (129). In a synthesis of phyllocladene from abietic acid... 

Efficient preparation of dicarboxylic acid 1275 <2001J(P1)1039> was the starting point of the novel, convenient synthesis of a known, central nervous system active 8-chloro-4//,6//-pyrrolo[l,2- r][4,IJbenzoxazepine 1276 (Equation 281). In the two-step synthesis the dicarboxylic acid 1275 was reduced to the diol, then this was treated with silica gel. Silica is acidic enough to promote elimination of water under mild conditions. In this way, compound 1276 could be prepared conveniently while the known methods (use of P2O5 or other strong acid) initiate serious side reactions of the pyrrole moiety. 

No 3-carboxy-substituted TBCs, derived from L-tryptophan by the Pic-tet-Spengler route, have yet been isolated from mammalian tissues. The same is also true for the dicarboxylic acid 23a derived from the condensation of L-tryptophan with pyruvic acid (36). The 1-carboxy-substituted TBCs 37 and 38, on the other hand, occur in mammalian systems (70,71) and are metabolically decarboxylated (65,S5). Whether a direct enzymatic decarboxylation of racemic material, occurring with the (S) and (R) enantiomers at a different rate, could account for the formation of unequal amounts of the enantiomers of TBC has not been investigated so far. The pyruvic acid route to optically active TBC (Fig. 12) leading from TBC 38a to TBC 29a via DBC 34 is at tifie moment the preferred pathway (85,86,89), although the enzymes involved in the asymmetric reduction leading to TBC 29a and the hydroxylated metabolites TBCs 30a and 33a have been neither isolated nor characterized. 

Diglycidyl ether of Bisphenol A (DGEBA) is a stiff monomer and in the reaction with aromatic or even aliphatic diamines it exhibits a very low tendency to cyclization, so that the ring-free theory can be applied with success. This conclusion was derived from the fact that the critical conversion at the gel point was independent of dilution for DGEBA-diamine systems and that the critical conversions correspond to the ring-free modelThe same conclusion applies to DGEBA-dicarboxylic acids systems... 

Electrolysis of the dicarboxylic acid (LVII) in an MeOH-MeONa-(Pt) system and subsequent workup afford the keto acid (LVIII), a precursor of chrysanthemic acid (LVffl), in 86% yield via intramolecular acyloxylation and acid-promoted hydrolysis [139] ... 

As seen in Scheme 1.4, LTB4 is further metabolized by terminal oxidation, first to the primary alcohol 2O-OH-LTB4, then to the dicarboxylic acid 2O-CO2H-LTB4, The terminal aldehyde is presumably an intermediate in the formation of the latter, but it has not yet been found in biological systems. 

The formula for the dicarboxylic acid (Figure 2.9) has a hydrophilic/lipophilic balance similar to that of octanoic acid, but the influence of the two acids on amphiphilic association structures is entirely different, as shown in Figure 2.10 [93], The octanoic acid causes the formation of a liquid crystal when added to a solution of water in hexylamine. The size of the lamellar liquid crystalline region is large (Figure 2.10a). Addition of the dicarboxylic acid, in contrast, gives no liquid crystal, and it may be concluded that its action in concentrated systems is similar... 

The polyamides (nylons) were given a special naming system. Nylons made from diamines and dicarboxyfic acids are designated by two numbers, the first representing the number of carbons in the diamine chain (a) and the second the number of carbons in the dicarboxylic acid (h). (See Figure 3.)... 

The nature of the acyl residues follows from the proton n.m.r. spectrum. INDOR measurements were used, wherein the methyl signals at 5 1.83,1.90, and 2.18 were chosen as monitoring lines. The methyl signal at d 1.83 is coupled with the olefinic proton at S 6.82, while the two others couple with that at 5 5.67, indicating exclusively allylic couplings. The former spin-system corresponds to the dicarboxylic acid. The chemical shifts fit mesaconic acid (5 6.69 and 5.76, respectively). The second spin-system is congruent with senecioic acid (5 1.87,... 

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