Carboxylic acids, from acyl carbon dioxide

The modified cephalosporin ceftobiprole (31-8), yet another compound that contains a double bond at the ring carbon, though in this case with a rather complex extended side chain, has shown activity in the clinic against some strains of multidrug resistant bacteria. The synthesis starts with the weU-precedented acylation of the cephalosporin (31-2), available in several steps from the commercially available 7-acetoxy cephalosporanic acid, with the activated thiadiazole carboxylic acid (31-1). The hydroxyl group in the product (31-3) is then oxidized with manganese dioxide to afford the corresponding aldehyde (31-4). This product is then condensed with the fcw-pyrrolidyl phosphonium salt (31-5), itself protected with the... 

Both indole-3-carboxylic and indol-2-yl-acetic acids are easily decarboxylated in boiling water. In each case carbon dioxide is lost from a small concentration of P-protonated 3//-indolium cation, the loss being analogous to the decarboxylation of a P-keto-acid. Indole-l-carboxylic acid also decarboxylates very easily, but is sufficiently stable to allow isolation and use in acylation reactions. Indole-2-carboxylic acids can only be decarboxylated by heating in mineral acid or in the presence of copper salts. °... 

Mixed anhydride method, a procedure of peptide coupling using reactive species resulting from the carboxylic moiety of a N-acylated amino acid and alkyl chlorocar-bonates (alkyl chloroformates), especially isobutyl chlorocarbonate (isobutyl chloro-formate), that readily reacts with an amino component. The nucleophilic amino component attacks the carboxy group of the amino acid component, with formation of the desired peptide derivative and release of the unstable isobutyl carbonic acid which immediately decomposes into carbon dioxide and isobutanol [J. Meienhofer, in The Peptides Analysis, Synthesis, Biology,... 

Acylating agents that have been employed are carbon dioxide, alkyl chloroformates, alkyl formates, add chlorides, esters, benzonitrile and dimethylformamide the expected acylation products from reaction with the above reagents were formed in each case. However, the N,N-dimethyl-amide derivatives of higher carboxylic acids did not yield acylated product as in the case of dimethylformamide . When R = H (equation 63), it was necessary to employ two equivalents of the lithiodithiane due to product enolate formation. 

The triethylamine salt of a carboxylic acid, prepared by the reaction of triethylamine and a carboxylic acid 1372, undergoes reaction with one-sixth of an equivalent of triphosgene to give an equimolar mixture of the carboxylate and the predicted intermediate acyl chloroformate 1373 [1042]. Nucleophilic displacement of the chloroformate function by the carboxylate affords the desired anhydride 1374, with concomitant formation of triethylammonium chloride as a precipitate and carbon dioxide gas. The reaction reaches completion in minutes. The solvents of choice have been THF or ethyl acetate, and no evidence for the formation of diacyl carbonates as potential by-products of the reaction has been found. The reaction has been used to prepare the anhydrides from both electron-rich and electron-deficient carboxylic acids (see below) [1042]. 

Fatty acid biosynthesis utilizes acetyl CoA. Radioactive acetate is the common experimental substitute, but in the developing seed sucrose from the mother plant is the initial source of substrate. Biosynthesis is a multi-step process (Fig. 3.14) which firstly involves the formation of malonyl CoA by carboxylation of acetyl CoA with carbon dioxide. This malonyl CoA is then accepted by acyl carrier protein (ACP) which is part of a multienzyme complex called the ACP fatty acid synthetase complex. The malonyl CoA is then condensed with... 

The direct reaction of indoles with carbon dioxide at atmospheric pressure to give the 3-carboxylated derivatives has been reported. The reaction occurs in dimethyl for-mamide in the presence of a large excess in lithium t-butoxide whose function is to deprotonate the indole. Although the N-H proton is more acidic, the C(3) anion yields the thermodynamically more stable carboxylated product. Acyl transfer from amides, such as A-(4-nitrophenyl)acetamide to benzene may occur in triflic acid. The mechanism is likely to involve diprotonation of the amide, as shown in (39), and dissociation of the C-N bond to give an acyl cation. The methodology allows the formation of aromatic ketones by inter- or intra-molecular reaction. The acylation of arenes may also be... 

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