Methyl ester cleavage reaction

Ketone body synthesis occurs only in the mitochondrial matrix. The reactions responsible for the formation of ketone bodies are shown in Figure 24.28. The first reaction—the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA—is catalyzed by thiolase, which is also known as acetoacetyl-CoA thiolase or acetyl-CoA acetyltransferase. This is the same enzyme that carries out the thiolase reaction in /3-oxidation, but here it runs in reverse. The second reaction adds another molecule of acetyl-CoA to give (i-hydroxy-(i-methyl-glutaryl-CoA, commonly abbreviated HMG-CoA. These two mitochondrial matrix reactions are analogous to the first two steps in cholesterol biosynthesis, a cytosolic process, as we shall see in Chapter 25. HMG-CoA is converted to acetoacetate and acetyl-CoA by the action of HMG-CoA lyase in a mixed aldol-Claisen ester cleavage reaction. This reaction is mechanistically similar to the reverse of the citrate synthase reaction in the TCA cycle. A membrane-bound enzyme, /3-hydroxybutyrate dehydrogenase, then can reduce acetoacetate to /3-hydroxybutyrate. 

These products undergo cleavage of the C—N bond on reaction with various nucleophiles. Thus they are converted in high yield to methyl esters on reaction with NaOCH, in CH,OH. They are rtJJuced to aldehydes by NaBH4 in about 80% yield. They react with R Li or R MgCl to form tertiary alcohols, RC(OH)R, in 55-75% yield. Reaction with 2, results in secondary amides, RCONHR, in -85%> yield, useful for conversion of primary amides to a variety of products... 

It took another 35 years until the first (and still the only known) enantioselective total synthesis of (/ )-ochratoxin a (326), and therefore of ochratoxins A and B, was published by Gill et al. in 2002 (264, 265). Scheme 6.1 shows six steps of the nine-step synthesis, which was achieved with 10% overall yield. The first three steps of the procedure are not shown and comprise the preparation of 327 from (/ )-2-methyloxirane according to ref. (266). Ketene dimethyl acetal and acetylenic ester 327 react in an intermolecular cycloaddition to give 328. This diene undergoes a Diels-Alder reaction with methyl propiolate to yield 329. Lactonization ( 330), demethylation ( 331), chlorination ( 332), and methyl ester cleavage finally furnished enantiomerically pure ochratoxin a (326) (267). 

Zhou et al. [177] use a random copolymer of tetrahydropyranyl methacrylate (THPMA) and methyl methacrylate (MMA) polymer doped with BSB-S2 as the PAG for microfabrication. At the laser focal spot, the THPMA groups were converted to carboxylic acid groups due to photogenerated acid-induced ester cleavage reactions, and were therefore rendered soluble in aqueous base developer. Figure 45 shows the 3D microstructure produced by this method. By two-photon fluorescence imaging, it was found that the buried channels are open and a continuous connection was made between the two cavities. 

Methyl esters (RCO2CH3) undergo a cleavage reaction to yield carboxylate ions plus iodomethane on heating with Lil in dimethylformamide ... 

From intermediate 43, the path to monensin would seemingly be straightforward. A significant task which would remain would be the construction of the l,6-dioxaspiro[4.5]decane substructure of monensin. You will note that the oxygen atoms affixed to carbons 5 and 12 in 43 reside in proximity to the ketone carbonyl at C-9. In such a favorable setting, it is conceivable that the action of acid on 43 could induce cleavage of both triethylsilyl ethers to give a keto triol which could then participate in a spontaneous, thermodynamically controlled spiroketalization reaction. Saponification of the C-l methyl ester would then complete the synthesis of monensin. 

In the IR spectrum of the acidified polymer, the weak carboxylate band near 1560 cnT1was replaced with a new, weak carbonyl band at 1701 cm"1, attributable to methacrylic acid residues. Apparently a side-reaction, probably involving some crosslinking of the copolymer and/or formation of a new ester, was occurring in addition to cleavage of the methyl ester. 

A variation on the usual synthesis of pyrazines, reaction of 1,2-diones with diamines, was the use of the diazabutadiene 81 in place of the dione <06JOC5897>. In another paper, the same diaza compound 81 reacted with sarcosine methyl ester, in a complex set of reactions, to produce quite good yields of 5-oxy-pyrazine-2-carboxamides 82. The A-methyl was lost and direct aromatisation occurred, presumably, due to cleavage oftheN-N bond <06SL2403>. 

The analytical control of this step is of special importance the alcaline saponification is performed at a relatively low pH in order to prevent cleavage of the silicon-carbon bond. The closer the electron-with-drawing carboxyl group is located to the Si-C-bond, the larger is the danger of scission. Therefore, for the B-silyl carboxylic acid derivatives the pH during saponification should not surpass 10.5 however, at this pH saponification of the methyl ester requires about 1 day, even at 60°C. For the -silyl derivatives, the pH of the reaction mixture is not critical. We therefore now exclusively utilize the latter. 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

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