And oxidative decarboxylation

Figure 9-4. Metabolism of the branched-chain amino acids. The first two reactions, transamination and oxidative decarboxylation, are catalyzed by the same enzyme in all cases. Details are provided only for isoleucine. Further metabolism of isoleucine and valine follows a common pathway to propionyl CoA. Subsequent steps in the leucine degradative pathway diverge to yield acetoacetate. An intermediate in the pathway is 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), which is a precursor for cytosolic cholesterol biosynthesis.

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

It may be difficult to imagine the alkylation of a 3,5-dialkoxyphenylcarbanion in which no ortho chelators are available to assist deprotonation at the desired position, not to mention the disjoint relationship of this donor carbon to the oxy substituents present. A solution to this problem is provided by redox manipulations and incorporation of a removable acceptor group to affirm the donor site. Thus, the Birch reduction product of 3,5-dimethoxybenzoic acid readily undergoes alkylation, and oxidative decarboxylation generates the aromatic compound [273]. 

Reactions between 3(2//)-isoquinolinones and substituted maleic anhydrides, after hydrolysis of the adducts and oxidative decarboxylation, result in derivatives bridged with an unsaturated carbon chain (34)... 

Alpha oxidation and omega oxidation. Animal tissues degrade such straight-chain fatty acids as palmitic acid, stearic acid, and oleic acid almost entirely by (3 oxidation, but plant cells often oxidize fatty acids one carbon at a time. The initial attack may involve hydroxylation on the a-carbon atom (Eq. 17-3) to form either the d- or the L-2-hydroxy add.17 18-32 323 The L-hydroxy acids are oxidized rapidly, perhaps by dehydrogenation to the oxo acids (Eq. 17-3, step b) and oxidative decarboxylation, possibly utilizing H202 (see Eq. 15-36). The D-hydroxy acids tend to accumulate... 

Degradation of amino acids most often begins with conversion, either by transamination3563 or by NAD+-dependent dehydrogenation,357 to the corresponding 2-oxoacid and oxidative decarboxylation of the latter (Fig. 15-16). Alanine, valine, leucine, and isoleucine are all treated this way in the animal body. Alanine gives pyruvate and acetyl-CoA directly, but the others yield CoA derivatives that undergo... 

Proof for the existence of benzene isomers in irradiated benzene has been obtained in several ways. These will not be discussed in detail, but they may be classified broadly as physical and chemical. Nuclear magnetic resonance has been used by Wilzbach and Kaplan to identify benzvalene.39 Prismane has also been identified by NMR and by vapor-phase chromatography. The Dewar form has been synthesized in several steps which start with ris-1,2-dihydrophthalic anhydride. Photochemically this compound yields bicyclo(2,2,0)hexa-5-ene-2,3-dicarboxylic aqid anhydride. This was followed by catalytic reduction and oxidative decarboxylation to give the Dewar form of benzene.39 The method of synthesis alone provides some basis for structure assignment but several other bits of supporting evidence were also adduced. Dewar benzene has a half-life of about 48 hr at room temperature in pyridine solution and its stability decreases rapidly as the temperature is raised. 

Ni(CO)4 in CH3OH to give a mixture of la and lb which was converted into the cyclopentenone 2. Final steps involved hydrolysis and oxidative decarboxylation. 

The 1,2-oxides of benzoic acids are also of interest as possible intermediates in the ortho hydroxylation and oxidative decarboxylation of aromatic acids. Ultraviolet studies indicate that benzene oxide 218 predominantly exists as its... 

Phenylpyruvate can be reduced to phenyl lactate and oxidatively decarboxylated to phenylacetate. both of which are also excreted in the urine. 

Subsequent metabolism of oxaloacetate (OAA) varies according to species. Three main types of C4 pathway are recognized, of which the most extensively studied is that shown by plants such as Zea mays (corn) (Fig. 2). In these plants (here called type-1 C4 plants) OAA is reduced to malate via NADP-malate dehydrogenase in mesophyll chloroplasts. Malate is then transported to bundle sheath chloroplasts and oxidatively decarboxylated by NADP-malic enzyme to produce pyruvate, CO2 and NADPH. Pyruvate is recycled to the mesophyll cells while the CO2 and NADPH are used in the RPP cycle in the bundle sheath chloroplast. The original C3 carbon acceptor (PEP) is regenerated from pyruvate in the mesophyll chloroplast by the activity of pyruvate, Pj dikinase [8] (Eq. 5). 

The total synthesis of complicated polycyclic closed-shell cage compounds represents one of the top achievements of modern synthesis. Progress in this area is mainly due to the ingenious use of the Diels-Alder cycloaddition, as is illustrated in the synthesis of basketene 357 (Scheme 2.123). " In this case the Diels-Alder reaction between diene 358 (the valent isomer form of cyclooctate-traene) and maleic anhydride leads in one step to the construction of the tricyclic structure 359 in quantitative yield. Subsequent [2 -I- 2] cycloaddition (see below) leads to product 360, which has the required structure but additional substituents. Saponification and oxidative decarboxylation of 360 gives basketene 357. 

The degradative pathways of valine and isoleucine resemble that of leucine. After transamination and oxidative decarboxylation to yield a CoA derivative, the subsequent reactions are like those of fatty acid oxidation. Isoleucine yields acetyl CoA and propionyl CoA, whereas valine yields CO2 and propionyl CoA. The degradation of leucine, valine, and isoleucine validate a point made earlier (Chapter 14) the number of reactions in metabolism is large, but the number of kinds of reactions is relatively small. The degradation of leucine, valine, and isoleucine provides a striking illustration of the underlying simplicity and elegance of metabolism. 

The degradative pathways of valine and isoleucine resemble that of leucine. After transamination and oxidative decarboxylation to yield a CoA derivative, the subsequent reactions are like those of fatty acid oxidation. Isoleucine yields acetyl CoA and propionyl CoA, whereas valine yields... 

Isoleucine and valine. The first four reactions in the degradation of isoleucine and valine are identical. Initially, both amino acids undergo transamination reactions to form a-keto-/T methyl valerate and a-ketoiso valerate, respectively. This is followed by the formation of CoA derivatives, and oxidative decarboxylation, oxidation, and dehydration reactions. The product of the isoleucine pathway is then hydrated, dehydrogenated, and cleaved to form acetyl-CoA and propionyl-CoA. In the valine degradative pathway the a-keto acid intermediate is converted into propionyl-CoA after a double bond is hydrated and CoA is removed by hydrolysis. After the formation of an aldehyde by the oxidation of the hydroxyl group, propionyl-CoA is produced as a new thioester is formed during an oxidative decarboxylation. 

Little data is available, but methyl groups a and y to ring nitrogens appear to be activated. 2-Methyl and 6-methyl substituents in pyrido[3,2-d]pyrimidines undergo bromination36,79 123 and oxidative decarboxylation,23 and form styryl compounds.23 The 6-methyl group in pyrido[2,3-d]pyrimidines could not be brominated.78... 

Isoleucine is a good example of branched-chain amino acids for a semi-in-depth examination. Unique aspects of the metabolism of valine and leucine are highlighted. After transamination and oxidative decarboxylation to form the branched-chain fatty-acyl CoA, a double bond is formed between a and b carbons utilizing FAD then water is added to form a b hydroxy derivative (Fig. 18.4). Then a NAD+-dependent dehydrogenase produces a keto derivative of the branched-chain fatty-acyl CoA. The similarity to straight-chain fatty-acid oxidation should be noted. This keto fragment is cleaved with participation of coenzyme A to form acetyl CoA, which ei-... 

Other radical sources involve hydrogen abstraction from alkyl formates [Eq. (25)] and oxidation decarboxylation of semiesters of oxalic acid [Eq. (26)]... 

L-hydroxy acids are oxidized rapidly, perhaps by dehydrogenation to the 0x0 acids (Eq. 17-3, step b) and oxidative decarboxylation, possibly utilizing H2O2 (see Eq. 15-36). The D-hydroxy acids tend to accumulate... 

FIGURE 22.2 The a oxidation and oxidative decarboxylation of a branched-chain fatty acid allow generation of intermediates that can enter normal oxidative pathways. 

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