Reduction hydroxyl

There does exist one prominent exception to the generalization 95> that the dl pinacol heavily predominates in reductions carried out in alkali. When the aromatic ring bears a phenolic hydroxyl, reduction in alkali affords the meso pinacol exclusively. Thus reduction of 93 produces a mixture of dl and meso pinacols, but 94 affords the pure meso pinacol90). Other aromatic car-... 

A particular isozyme can perform several types of reaction, including hydroxylations, reductions, O-dealkylations and epoxidations.65 The most important reactions for CAC are hydroxylations and epoxidations. A CYP isozyme can also catalyse different reactions of different substrates. CYP1A, to give an example, can O-dealkylate ethoxyresorufine or hydroxylate benzo[a] pyrene. 

Chronic exposure to cimetidine may be associated with gynecomastia in males and galactorrhea in females, possibly resulting from the drug s affinity for the androgen receptors combined with CYP inhibition of estradiol hydroxylation. Reductions in sperm count and impotence have been described in men chronically receiving the drug. 

Selective reduction of m-dinitrobenzene (121) followed by, successively, diazotiza-tion, introduction of hydroxyl, reduction of the nitro group and carboxylation, yields the antimycobacterial agent p-aminosalicylic acid (122) (Scheme 25) used with the antibiotic streptomycin. A three-step synthesis starting with toluene yields the inexpensive drug thioacetazone (123). 

Reduction of phenolic ketones. The carbonyl group of hydroxyacetophenones can be reduced with boiling aqueous alkaline sodium borohydride. When the carbonyl group is ortho or para to a phenolic hydroxyl reduction proceeds to the methylene derivative (1 — 2), but stops at the carbinol stage when the phenolic hydroxyl and carbonyl group are me/a-oriented (3 — 4).5... 

Phase I reactions, which often create anchor points in the xenobiotic molecule for subsequent conjugation, comprise oxidations (electron removal, dehydrogenation and hydroxylation), reductions (electron donation, hydrogenation and removal of oxygen), and hydrolytic reactions. Many metabolic reactions take place in the endoplasmic reticulum of the liver cells. Other organs, particularly kidneys and lungs, also participate in drug metabolism. In addition, a variety of other tissues (brain, skin, intestinal mucosa) have the capacity to metabolize xenobiotics. 

The pathways ot xenobiotic metabolism are divided into two major categories. Phase 1 reactions (biotranstormations) include oxidation, hydroxylation, reduction, and hydrolysis. In these enzymatic reactions, a new functional group Is Introduced Into the substrate molecule, an existing functional group is modified, or a functional group or acceptor site tor Phase 2 transfer reactions Is exposed, thus making the xenobiotic more polar and, therefore, more readily excreted. 

The three major monolignols (Fig. 9.2) used to synthesize lignin polymers are formed in the cytoplasm via the shikimate pathway which produces phenylalanine as key intermediate [7-9]. Through further enzyme mediated deamination, hydroxylation, reduction and methylation reactions, the final lignin precursors are formed as depicted in Fig. 9.3. 

Scheme 73 Iminium-catalyzed one-pot P-hydroxylation-reduction procedure for the syntheses of chiral P-diols...

In vitro, the presence of 800 mM iron increased (> 100 %) the production of HO by 5 pM 6-hydroxydopamine while Mn caused a significant reduction (72%) (Mendez-Alvarez etal. 2001). The presence of ascorbate (100 pM) induced a continuous generation of HO while the presence of hydroxyl reductants (100 pM) limited this production to the first minutes of the reaction. In vivo, tyrosine hydroxylase immunohistochemistry revealed that intrastriatal injections of rats with 6-hydroxydop-amine (30 nmol) + (600 nmol), 6-hydroxydopamine -I- ascorbate -i- Fe (5 nmol), and 6-hydroxydop-amine -i- ascorbate -t Mn (5 nmol) caused large striatal lesions, which were markedly reduced (60%) by the substitution of ascorbate by l-cysteine. Injections of Fe or Mn alone showed no significant difference to those of saline. 

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