Hydroxy la tion

As an example of the first type of chiral effect, metabolism of the drug bufuralol may be considered. Hydroxy la tion in the V position only occurs with the (+) isomer, whereas for hydroxylation in positions 4 and 6, the (—) isomer is the preferred substrate (Fig. 5.3). Glucuronidation of the side chain hydroxyl group is specific for the (+) isomer. A further complication in human subjects is that the 1-hydroxylation is under genetic control, being dependent on the debrisoquine hydroxylator status (see below). The selectivity for the isomers for the hydroxylations is virtually abolished in poor metabolizers. 

A further extension of m-xylyl dicopper complexation and xylyl hydroxy la-tion is seen in a Schiff-base macrocycle [175], When dicopper(I) complex 38 is reacted with 02, one of the two arene rings is hydroxylated, again producing a phenoxo-bridged dicopper(II) species a peroxo-dicopper(II) intermediate is suggested as the actual oxidant. 

The lactone (464) was reduced with lithium aluminium hydride to the (20/ )-18,20-diol. Regeneration of the A -3-keto-group afforded the keto-diol (465). Catalytic hydrogenation in alkaline medium selectively reduced the double bond at C(4) and gave the desired configuration of 5)5-H. Acetylation at C(18) was followed by oxidation, which provided the diketo-pregnane (466). Hydroxy-la tion of the -double-bond of (466) with osmium tetroxide gave the 3a,9a-... 

The basic permanganate oxidation of conjugated 1,3-dienes is different from those reported for the 1,4-dienes above. Therefore, in the oxidation of cyclopentadiene and 1,3-cyclohexadiene (13) a mixture of five products 14-18 is obtained (equation 4) . In this reaction 14 and 16 are derived from the normal cis hydroxy la tions whereas 17 and 18 were said to be formed from 15 by hydration in what the authors term an epoxidic pathway. Formation of epoxy-diols under similar permanganate oxidations has been found for occidentalol (19), levopimaric acid (20) and a 1-chloro- or 1-bromo-l,3-diene (21) as an intermediate step in the synthesis of (+)-D-c/tfrc-3-inosose and (+)-D-c/r/ro-3-inositol (equation 5). The explanation for the epoxide formation in the oxidation of 1,3-dienes (13, 19-21) is not clear but may be connected to the fact that other additions of permanganate to dienes are possible beyond those commonly observed... 

The effect of N20 on x-ray induced hydroxy la tion and degradation of benzoic acid could be explained by suppression of Reaction 10 and thus of Reaction 14 ... 

Aq. SO -HaOa added dropwise below 35° during 1.5 hrs. to a stirred soln. of 2,6 diamino-3 nitrosopyridine in trifluoroacetic acid, and stirred 6-11 hrs. at room temp. -> 2,6 diamino-3-nitropyridine. Y 96%. — Similarly with simultaneous C - hydroxy la tion 4,6-Diamino - 5 - nitrosopyrimidine 4,6 - diamino - 2-... 

All nucleophilic substitutions show that in pyridine and its derivatives as free bases the 2- and 4-positions are more reactive than the 3-position. Organometallic compounds generally effect 2-substitution (pp. 200, 220) and the Tschitschibabin amination and hydroxy la tion reactions also occur mainly at C(2) (pp. 206, 234). However, these reactions cannot be taken to imply superior electrophilic power in C(2) as compared with C(4), for the issue is confused in each case by mechanistic problems as well as the precise nature of the reagent, that of the initial step is uncertain, and subsequent stabilization of one transition state rather than another by the formation of an addition compound may be occurring. As evidence about the intrinsic electrophilic properties of individual nuclear positions these reactions are valueless. 

Metabolic Hydroxy la tion of Drugs and Other Organic Sub-... 

Three examples are given to demonstrate the feasibility of electroorganic synthesis on BDD anodes. The first example is the oxidation of phenol to benzoquinone [6], an important intermediate in fine organic synthesis. The second example is the oxidation of 3-methylpyridine (3 MP) to nicotinic acid [7], an important pharmaceutical intermediate, and the third example is the hydroxy la tion of salicylic acid [5], a typical example of an electrochemical hydroxylation. 

The combined action of lithium in liquid ammonia and carbon dioxide upon androst-4-en-3-one led to a synthesis of the /3-keto-ester (189), after esterification of the intermediate acid the reaction is one of reductive methoxycarbonyla-tion.82 Alkylation of the keto-ester (189) afforded a separable mixture of the 4/3-methyl steroid (190) as the major product (55%) and the corresponding 4a-methyl epimer. Reduction of the steroid (190) led to 4a-hydroxymethyl-4/3-methyl-5a-androstan-3/3-ol. Finally in this section, it has been noted that vinyl-magnesium bromide effects 1,4-addition to the a(3-unsaturated ketone 17/3-hydroxy-5a-androst-l-en-3-one to yield la-vinyl-5a-androstan-3-on-17/3-ol, which could be further reduced to the la-ethyl-3-ketone.83... 

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