Bioactivation oxidation reactions

Chlorogenic acids are shown to have some desirable biological activities. Most of their property relates to their function as antioxidants, evidenced by their activity to scavenge free radicals, to inhibit the formation of free radicals, and to block the oxidation reaction. However, other activities based on mechanisms other than scavenging capacity cannot be ignored. Also, further tests for the in vivo bioactivity of chlorogenic acids are to be needed. However, it is expected that chlorogenic acids may be beneficial to human health. 

This is the case with NAD(P)H-dependent dehydrogenases, where enzymes find applications in several synthetic processes (comprising the reduction of aldehydes, ketones, carboxylic acids, double, and triple carbon-carbon bonds), aimed at the preparation of chiral enantiopure bioactive compounds and of building blocks for fine chemicals and pharmaceutical products. Moreover, dehydrogenase-catalyzed oxidation reactions are gaining increasing interest as an environmentally friendly alternative to chemical oxidation processes, especially in those cases where a defined selectivity (either stereo-, regio-, or chemoselectivity) is required as well [1]. 

Neither retinol nor the provitamin A carotenoids are directly bioactive. Retinol must be activated in a series of oxidative reactions, while the provitamin A carotenoids must first be cleaved to produce retinol. Of numerous metabolites of vitamin A, two are well... 

Deprotection of X, and subsequent oxidation, reduction, and acetylation reactions can, with care, be carried out without decomposition of the inorganic backbone. Reactions of this type are of particular interest for the synthesis of bioactive or biocompatible polyphosphazenes. 

The antioxidant and pro-oxidant nature of lycopene chemistry has been hypothesized by some to be the principle bioactivity that drives its cellular consequences. It is important to describe these reactions and the variety of circumstances that cause lycopene to act as a pro-oxidant or an antioxidant because the cell culture environment might be quite different from what is generally encountered by prostate cells within the intact healthy prostate or tumor areas. 

Coumarins are known to have pronounced bioactivity. A rather new procedure for the synthesis of pyrrolo[3,2-c]coumarins uses a domino process in which an amine oxide rearrangement [61] is involved (Scheme 7.37) [62]. Reaction of the cou-... 

Abiotic spoilage is produced by different physical and chemical changes such as hydrolytic action of enzymes, oxidation of fats, breakdown of proteins, and a browning reaction between proteins and sugars. However, in this chapter we focus on microbial deterioration and their effects on bioactive compounds. 

Oxidations of 9-Hydroxyellipticine. 9-Hydroxyellipticine is the major metabolite of ellipticine formed by mammalian cytochrome P-450 hydroxylation (147,153). The reaction is a good example of a bioactivation process because 9-hydroxyellipticine is many times more active as an antineoplastic agent than is ellipticine itself (154). Auclair, Meunier, Paoletti, and co-workers have extensively studied further oxidations of 9-hydroxyellipticine and its derivatives (155-158). 

The metabolism of 77-hexane takes place in the liver. The initial reaction is oxidation by cytochrome P-450 isozymes to hexanols, predominantly 2-hexanol. Further reactions convert 2-hexanol to 2-hexanone, 2,5-hexanediol, 5-hydroxy-2-hexanone, 4,5-dihydroxy-2-hexanone and the neurotoxicant 2,5-hexanedione. Hydroxylation at the 1- and 3- positions can be considered detoxification pathways hydroxylation at the 2- position is a bioactivation pathway. A diagram of the proposed pathway for mammalian metabolism of -hexane is presented in Figure 2-3. 

For many of the drugs associated with hepatotoxicity, there are examples of structurally related drugs which are latent to bioactivation and toxicity because of the absence of the toxicophore or the existence of alternate metabolic pathways. For example, the hepatotoxicity associated with the use of the anti-Parkinson s agent tolcapone does not occur with the structurally related drug entacapone, despite administration at doses similar to tolcapone (200-1000 mg QD). This disparity may be explained in part by the observation that entacapone does not succumb to the bioactivation reactions of tolcapone in humans (Scheme 15.3) [35]. It is also noteworthy that tolcapone but not entacapone is a potent uncoupler of oxidative... 

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