Carboxy-hydroxy-elimination

Decarboxylation of (3-Hydroxy Carboxylic Acids and of (3-Lactones Carboxy-hydroxy-elimination... 

Metabolism is the major route of elimination of THC from the body as little is excreted unchanged. In humans, over 20 metabolites have been identified in urine and feces 26 Metabolism in humans involves allylic oxidation, epoxidation, aliphatic oxidation, decarboxylation, and conjugation. The two monohydroxy metabolites (Figure 4.7) 11-hydroxy (OH)-THC and 8-beta-hydroxy THC are active, with the former exhibiting similar activity and disposition to THC, while the latter is less potent. Plasma concentrations of 11-OH-THC are typically <10% of the THC concentration after marijuana smoking. Two additional hydroxy compounds have been identified, namely, 8-alpha-hydroxy-THC and 8,11-dihydroxy-THC, and are believed to be devoid of THC-like activity. Oxidation of 11-OH-THC produces the inactive metabolite, ll-nor-9-carboxy-THC, or THC-COOH. This metabolite may be conjugated with glucuronic acid and is excreted in substantial amounts in the urine. 

Disposition in the Body. Readily and almost completely absorbed after oral administration. More than 60% of a dose is excreted in the urine in 24 hours, including about 9% of the dose as the 2-hydroxy metabolite, 2-[4-(2-hydroxy-2-methylpropyl)phenyl]-propionic acid, about 17% as the conjugated hydroxy metabolite, about 16% as the 2-carboxy metabolite, 2-[4-(carboxypro-pyOphenyljpropionic acid, and about 19% as the conjugated carboxy metabolite (both metabolites are inactive) less than 10% of a dose is excreted unchanged. The remainder of the dose is probably eliminated in the faeces after excretion in the bile excretion is virtually complete within 24 hours. 

The preparation of arylazo derivatives from hydroxypyrazines has been described in Section VI.6E and from l,4,6-trimethyl-3-methylene-2-oxo-l,2,3,4-tetrahydro-pyrazine to give l,4,6-trimethyl-2-oxo-3-phenykzomethylene-l,23,4-tetrahydro-pyrazine in Section VI.9B. In addition to these reactions Princivalle (1122) reports that 2reacted with benzenediazonium chloride and p-toluenediazonium chloride by elimination of the carboxy group para to the hydroxy group and coupling to form 2-hydroxy-3,6-dimethyl-5-phenyl-azo(and p-tolueneazo)pyrazines, respectively (1122), identical to those prepared from 3-hydroxy-2,5 -dimethylpyrazine. 

Among the different methods for the formation of C-C double bonds, the reductive elimination of (3-functionalized (mainly P-hydroxy or (3-carboxy) sulfones, is one of the most widely used ones in organic synthesis. The reductive elimination of (3-hydroxy sulfones and derivatives is the so-called Julia,94 or Julia-Lythgoe olefination reaction (Eq. 2). It usually involves a condensation between the anion of an alkyl sulfone and a carbonyl compound to afford a (3-hydroxy sulfone (Eq. 47). The metal alkoxide intermediate is typically transformed in situ into a carboxylic or sulfonic ester derivative, which is then reduced... 

Tables 18.1,18.2, and 18.3 hst concentration measurements madeatdiEferenttimes during regular classes, final exams, and the summer when few students were present, respectively. A -Tetrahydrocannabinol (THC) is the major psychoactive compound in marijuana. THC is rapidly oxidized to 11-hydroxy THC and then to ll-nor-9-carboxy-A -THC, which is the main metabolite excreted. The main metabolic route of cocaine involves the hydrolysis of ester linkages to produce benzoylecgonine (BE). 6-Acetylmorphine is the main specific metabolite of heroin (3,6-diacetylmorphine). Codeine is O3 -methylmorphine. Morphine-3 p-glucuronide is a metabolite formed in vivo by the attachment of a sngar to the O3 oxygen, which facilitates elimination of morphine from the body. All three of these morphine-based derivatives are narcotics. 3,4-Methylenedioxymethamphetamine (MDMA) and 3,4-metltylenedioxy-amphetamine (MDA) are amphetamine derivatives that are commonly referred to as ecstasy.

The capsular polysaccharide of Klebsiella type 47 contains side-chains attached to the main chain by way of D-glucuronic acid residues.The side-chains were removed to give a linear polysaccharide by the following sequence of reactions (i) substitution of hydroxy- and carboxy-groups with methyl vinyl ether, (ii) /S-elimination by treatment with base, and (iii) removal of modified uronic acid residues and protecting groups by mild hydrolysis with acid. 

Direct polycondensation in the bulk through the reaction of hydroxy and carboxy functionalities of the lactic acid monomer with the elimination of water molecule has all the drawbacks associated with the character of an equilibrium step-growth polymerization. In addition, employing this polymerization method, the stereoregularity of the polymer cannot be controlled. This polymerization technique involves the use of a catalyst and reduced pressure. " ... 

In this chapter, we first introduce the system of naming carboxylic acids and then list some of their physical and spectroscopic characteristics. We then examine their acidity and basicity, two properties that are strongly influenced by the interaction between the electron-withdrawing carbonyl group and the hydroxy function. Methods for the preparation of the carboxy group are considered next, followed by a survey of its reactivity. Reactions of carboxylic acids will feature a new two-step substitution pathway, addition-elimination, for the replacement of the hydroxy group by other nucleophiles, such as halide, alkoxide, and amide. The chemistry of the carboxylic acid derivatives, which result from these transformations, is the subject of Chapter 20. 

The a,p-double bond in amino acid derivatives and peptides represents, in addition to the amino and carboxy groups, the introduction of a third highly reactive function into the molecule. It is therefore pertinent in a discussion of the a,P-dehydroamino acids to devote some attention to their primary addition products, such as derivatives of a-mercapto- and a-hydroxy-a-amino acids. Further topics relevant in this context are their relationship to P-hydroxy- and P-mercapto-a-amino acid derivatives (elimination-addition sequence), as well as syntheses and reactions of pyruvoylamino acids, which result from the hydrolysis of dehydropeptides and can possibly serve as precursors of the latter by condensation with amino acid amides. On the other hand, p,y- and y S-dehydroamino acids will be excluded from the scope of this discussion. The isolated double bonds of these compounds undergo the normal olefin reactions and display no unusual characteristics. 

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