Side-chain oxidized derivatives

Side-Chain Oxidized Derivatives of Ascorbic Acid... 

Side-chain oxidized derivatives of ascorbic acid are also implicated in the catabolism of ascorbic acid in plants. Loewus et al. (62) have established the intermediacy of ascorbic acid in the biosynthesis of tartaric acid in the grape. Labeling studies have established a metabolic pathway that must involve C5 and C6 oxidation of ascorbic acid. 

Of the possible side-chain oxidized derivatives of ascorbic acid, all but 5-keto-ascorbic acid and 5-keto-6-formylascorbic acid have been reported. Bakke and Theander (66) formed 6-aldehydoascorbic acid, 37, as an unisolated intermediate in the reductive hydrolysis of 38 to ascorbic acid. Heyns and Linkies (67) synthesized 5-keto-saccharo-ascorbic acid, 40, via the oxidation and subsequent hydrolysis of man-narodilactone, 39. 5-Ketosaccharoascorbic acid appears to exist in solution as its enol tautomer. 

The selection of one preferred route for dark secondary reactions from photogenerated cation radicals can also be seen in the products derived from 1-methylnaphthalene. Although ring cleavage is observed on irradiated Ti02 suspensions, side-chain oxidation of the corresponding radical cation takes place in homogeneous solution (Eq. 6) [61]. 

The predominance of nuclear methoxylation over competing alkyl side-chain oxidation processes for these systems was largely attributed to an intramolecular attack by the appended side-chain alkoxy radical on the anodically generated aromatic radical cation in the usual EEQCp mechanism [99]. A more recent mechanistic study of anodic oxidation of chiral alkoxynaphthalene derivative (LXXXIX) sheds some additional light on this process [Eq. (46)] [100]. The isolation of a 2 1 mixture of enantiomeric methoxylated products indicated that intramolecular attack by the appended alkoxy radical on the aromatic radical cation (path B) was disfavored at —7S°C (a nearly 1 1 mixture of enantiomers was obtained at 25 C), since the intermediate cyclic ketal resulting from such a process would be a meso form that would lead to a racemic mixture of methoxylated products. Note that the chirality of the appended hydroxyether side-chain disappears upon cycliza-tion to the acetal. 

Electrochemical oxidation of thiophene derivatives in methanol at a Pt anode leads to different types of reactions depending upon the electrolytes used. With sodium meth-oxide, 2,5-dimethyl- and tetramethylthiophene [207] afforded 2,5-dimethoxy adducts as a mixture of cisitrcms isomers together with side-chain oxidation products. However, in the presence of sodium acetate, the latter become the main products. In methanol/sulfuric acid solutions, at a carbon anode, thiophene and derivatives [208] oxidations resulted in a ringopening reaction with loss of the sulfur atom, yielding y-dicarbonyl compounds and their... 

A survey of work since 1975 on the derivatization of ascorbic acid is reviewed from the perspective of the organic chemistry of ascorbic acid. Recent advances in the control of regioselectivity of alkylative derivatization of ascorbic acid have been made possible by the utilization of di- and trianions of ascorbic acid. Their use has allowed the facile synthesis of inorganic esters of ascorbic acid. New synthesis of acetal and ketal, side-chain oxidized, and deoxy derivatives are reviewed. The total synthesis of a new side-chain oxidized ascorbic acid derivative, 5-ketoascorbic acid, is reported. 

The bile acids are 24-carbon steroid derivatives. The two primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the hepatocytes from cholesterol by hy-droxylation, reduction, and side chain oxidation. They are conjugated by amide linkage to glycine or taurine before they are secreted into the bile (see cholesterol metabolism. Chapter 19). The mechanism of secretion of bile acids across the canalicular membrane is poorly understood. Bile acids are present as anions at the pH of the bile, and above a certain concentration (critical micellar concentration) they form polyanionic molecular aggregates, or micelles (Chapter 11). The critical micellar concentration for each bile acid and the size of the aggregates are affected by the concentration of Na+ and other electrolytes and of cholesterol and lecithin. Thus, bile consists of mixed micelles of conjugated bile acids, cholesterol, and lecithin. While the excretion of osmotically active bile acids is a primary determinant of water and solute transport across the canalicular membrane, in the canaliculi they contribute relatively little to osmotic activity because their anions aggregate to form micelles. 

Apart from some nitration studies (Section IV,B), the only reaction of these derivatives to be described has been the side-chain oxidation of... 

Benzo[c] cinnoline aldehydes are as yet unknown. The 2- and 3-acetyl derivatives have been prepared, but the majority of known compounds relevant to this section are mono- and dicarboxylic acid derivatives. These include the 2-, - - 3-, ° and 4. - o2.J55,i57 monoacids and esters, the lactone of 10-hydroxybenzo[c]cinnoline-l-carboxylic acid, some halogeno- and methyl-substituted 2- and 4. carboxylic acids, and the 2,9-, 3,8-, - - and 4,7- dicarboxylic acids and derivatives. These compounds have been obtained by ring synthesis, or, in the case of 2-methylbenzo[c]dnnoline-9-carboxylic acid, by side-chain oxidation, " rather than by the introduction of substituents into benzo[c] cinnoline. Benzo[c]cinnoline-l-carbonitrile has been prepared, albeit in low... 

Oxidation of the primary and secondary alcohol groups on C-5 and C-6 could, theoretically, lead to a number of side-chain oxidised derivatives of L-ascorbic acid. Such compounds may not necessarily be prepared from ascorbic acid itself but C-2/C-3 protection would certainly be necessary if that were to be attempted. Some examples of this type of compound have been i.solated (Figure 4.15). 

Benzene derivatives as such do not absorb much light in the solar UV region however, in the presence of oxygen some of them form complexes (Chien, 1965 Khalil and Kasha, 1978 Onodera et al., 1980 Pasternak and Morduchowitz, 1983) that are susceptible to photolysis. It appears that the absorption spectra of the complexes tail into the solar UV region (Chien, 1965) and that the quantum yield for reaction is rather high. Products of the reactions include long-chain conjugated dialdehydes from benzene itself (Wei et al., 1967) and alcohols and aldehydes from side-chain oxidation of alkyl-substituted benzenes (Pasternak and Morduchowitz,... 

The main metabolites of ibuprofen, the glucuronides of ibuprofen and of the side-chain hydroxylated derivative 2-[4-(2-hydroxy-2-methylpropyl)phenyl]propionic acid) and a side-chain oxidized compound 2-[4-(2-carboxy-2-methylpropyl)phenyl]-propionic acid) could be detected after SPE using a 250-MHz instrument (Figure 8-2) [10]. 

Thiazine and dithiazine derivatives are expected to be metabolized primarily via side-chain oxidation and ring S- and A/-oxidation. 

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