What Is Decarboxylation

Thionyl chloride effectively causes —OH groups (for example, those of alcohols and carboxylic acids) to be replaced by Cl. Don t forget to show the by-products of the reaction (SO2 and HCl). 

Decarboxylation is the loss of CO2 from a carboxyl group. Almost any carboxylic acid, heated to a very high temperature, undergoes decarboxylation  

Most carboxylic acids, however, are quite resistant to moderate heat and melt or even boil without decarboxylation. Exceptions are carboxylic acids that have a carbonyl group p to the carboxyl group. This type of carboxylic acid undergoes decarboxylation quite readily 

Decarboxylation on moderate heating is a unique property of 3-oxocarboxylic acids (j8-ketoacids) and is not observed with other classes of ketoacids. 

STEP 1 Rearrangement of bonds. Redistribution of six electrons in a cyclic six-membered transition state gives carbon dioxide and an enol  

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Jencks and coworkers9 noted that a likely route for catalysis of carboxylation reactions (replacement of a proton by a carboxyl group) is the generation of low entropy carbon dioxide by a reaction of ATP and bicarbonate adjacent to Nl of biotin. This way of promoting carboxylation produces a situation which is precisely what is created at the stage of the initial formation of products in decarboxylation reactions. Since there is no directional momentum, the proximity of low entropy carbon dioxide and a nucleophile similarly will slow the reaction in the direction of decarboxylation. The same authors suggest that for decarboxylation reactions, nucleophilic addition to carbon dioxide in an enzyme s active site would prevent re-addition and promote the forward reaction if the addition product is itself sufficiently unstable. 

Pyridoxal phosphate is a coenzyme in amino acid decarboxylations. What is a likely mechanism of the decarboxylation, and what are the products ... 

Driven by decarboxylation. What is the role of decarboxylation in fatty acid synthesis Name another key reaction in a metabolic pathway that employs this mechanistic motif... 

An enzyme catalyzing the decarboxylation of lysine accepts only the isoelectric form as a substrate. What is the actual concentration of isoelectric lysine in a 10 M solution of lysine in a buffer at pH 7.60 ... 

Despite their enormous structural diversity, polyketide metabolites are related by their common derivation from highly functionalised carbon chains whose assemblies are controlled by multifunctional enzyme complexes, the polyketide synthases (PKSs) which, like the closely related fatty acid synthases, catalyse repetitious sequences of decarboxylative condensation reactions between simple acyl thioesters and malonate, as shown in Fig. 3 [7]. Each condensation is followed by a cycle of modifying reactions ketoreduction, dehydration and enoyl reduction. In contrast to fatty acid biosynthesis where the full cycle of essentially reductive modifications normally follow each condensation reduction, the PKSs can use this sequence in a highly selective and controlled manner to assemble polyketide intermediates with an enormous number of permutations of functionality along the chain. As shown in Fig. 3, the reduction sequence can be largely or entirely omitted to produce the classical polyketide intermediate which bears a carbonyl on every alternate carbon and which normally cyclises to aromatic polyketide metabolites. On the other hand, the reductive sequence can be used fully or partially after each condensation to produce highly functionalised intermediates such as the Reduced polyketide in Fig. 3. Basic questions to be answered are (i) what is the actual polyketide intermediate... 

Give an explanation for the relatively easy decarboxylation of pyridine-2-acetic acid what is the organic product ... 

The catalytic strategy is familiar from our discussion of PLP-dependent reactions reaction via a Schiff base, probable medium control of the decarboxylation, and desolvation of the carboxyl group on binding to the enzyme. What is most surprising is that pyruvate, with its very small electron sink, works as efficiently as PLP, which allows for more extensive electron delocalization. The specialness of PLP in enzymic catalysis must lie in other factors. 

The mechanism suggested by Kerscher and Oesterhelt is indicated in Scheme 46 for the enzyme from H. halobium (213). The initial step is identical to that of the 2-oxoacid dehydrogenase complexes and involves binding of pyruvate to thiamin diphosphate and subsequent decarboxylation yielding hydroxyethylthia-min diphosphate. This intermediate undergoes one-electron transfer to the [4Fe-4S] cluster to form the stable free radical. The cluster is then reoxidized by ferredoxin or oxygen to give the enzyme-intermediate complex. Reaction with CoA initiates the second electron transfer to the iron-sulfur cluster, acyl transfer, followed by reoxidation of the enzyme by ferredoxin or O2 to complete the cycle. Two basic questions are yet unanswered (1) What is the mechanism of the enzymic reaction between CoASH and hydroxyethyl-TPP in the absence... 

The probable mechanism of the enzymic decarboxylation of histidine can, at present, only be inferred from studies of the non-enzymic reactions discussed in the previous section, and from what is known of the mechanism of action of other pyridoxal phosphate-dependent enzymes. 

A compound named y-terpinene, an isomer of a-terpinene, is isolated along with the a isomer from the oils of a number of plant products. Upon ozonolysis, followed by an oxidative workup, yterpinene yields two compounds, one of which is 4-methyl-3-oxopentanoic acid. The second compound is an acid which decarboxylates upon heating and gives acetone. Two structures consistent with the data are possible for yterpinene. What are they On the basis of the isoprene rule, one of them can be discarded as highly improbable. What is the structure of y-terpinene ... 

Serotonin, or 5-HT, is biosynthesized (3) from its dietary precursor L-tryptophan (Fig. 14.1). Serotonergic neurons contain tryptophan hydroxylase (L-tryptophan-5-monooxygenase) that converts tryptophan to 5-hydroxytryptophan (5-HTP) in what is the rate-limiting step in 5-HT biosynthesis and aromatic L-amino acid decarboxylase (previously called 5-HTP decarboxylase) that decarboxylates 5-HTP to 5-HT. This latter enzyme also is responsible for the conversion of L-DOPA to dopamine (see Chapter 12). The major route of metabolism for 5-HT is oxidative deamination by monoamine oxidase (MAO-A) to the unstable 5-hydroxyindole-3-acetaldehyde, which is either reduced to 5-hydroxytryptophol ( 15%) or oxidized to 5-hydroxyindole-3-acetic acid ( -85%). In the pineal gland, 5-HT is acetylated by 5-HT N-acetyltransferase to N-acetylserotonin, which undergoes O-methylation by 5-hydroxyindole-O-methyltransferase to melatonin. 

Draw a curved-arrow representation of the bonding changes in the decarboxylation step of the reaction just shown. What is the relationship of the species formed in this step to the product ketone (Hint See Section 18.16.)... 

A very interesting development in this area is an application of crown chemistry to the malonic ester synthesis. A one-pot hydrolysis and decarboxylation procedure, using 18-crown-6 and potassium hydroxide in an organic solvent system, has been developed for esters with activating groups (Scheme 52). This procedure, which relies on the ability of 18-crown-6 both to catalyse ester hydrolysis and to facilitate decarboxylation under mild conditions, offers a simplification of what is often the yield-determining part of conventional malonate syntheses. 

A variation of the malonic ester synthetic uses a P-keto ester such as 116. In Section 22.7.1, the Claisen condensation generated P-keto esters via acyl substitution that employed ester enolate anions. When 116 is converted to the enolate anion with NaOEt in ethanol, reaction with benzyl bromide gives the alkylation product 117. When 117 is saponified, the product is P-keto acid 118, and decarboxylation via heating leads to 4-phenyl-2-butanone, 119. This reaction sequence converts a P-keto ester, available from the ester precursors, to a substituted ketone in what is known as the acetoacetic acid synthesis. Both the malonic ester synthesis and the acetoacetic acid synthesis employ enolate alkylation reactions to build larger molecules from smaller ones, and they are quite useful in synthesis. 

We have described what is commonly known as the acetoacetic ester synthesis and have illustrated the use of ethyl acetoacetate as the starting reagent. This same synthetic strategy is applicable to any j8-ketoester, as, for example, those that are available by the Claisen (Section 19.3A) and Dieckmann (Section 19.3B) condensations. For example, following are structural formulas for two jS-ketoesters available from Dieckmann and Claisen condensations that can be made to tmdergo (1) formation of an enolate anion, (2) alkylation or acylation, (3) hydrolysis followed by (4) acidification, and finally (5) decarboxylation just as we have shown for ethyl acetoacetate. 

Several substituted benzhydrols react with C of / -keto acids in 1,2-dichloroethane at 60 °C in the presence of an FeCl3 catalyst, giving the substitution product in what is thought to be an 5 1 reaction between the benzhydryl carbenium ion and a 0-keto acid. This is followed by a decarboxylation of the / -keto acid giving the final product, a (benzhydrylmethyl)alkyl- or aryl-ketone. The reaction also is successful when benzyl... 

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