Retro-acylation reaction

The retro-acylation reactions of B-ketoaldehydes (388, X=H), B-diketones (388, X=alkyl) and the retro-Claisen reaction of B-ketoesters (388, X=0R) occur through the formation of an intermediate 389 which gives an ester 390 and the enolate ion 391. Protonation of 391 then gives the corresponding aldehyde (392, X=H), ketone (392, X=alkyl) or ester (392, X=0R). 

Step 4 of Figure 29.3 Chain Cleavage Acetyl CoA is split off from the chain in the final step of /3-oxidation, leaving an acyl CoA that is two carbon atoms shorter than the original. The reaction is catalyzed by /3-ketoacyl-CoA thiolase and is mechanistically the reverse of a Claisen condensation reaction (Section 23.7). In the forward direction, a Claisen condensation joins two esters together to form a /3-keto ester product. In the reverse direction, a retro-Claisen reaction splits a /3-keto ester (or /3-keto thioester) apart to form two esters (or two thioesters). 

The retro-Claisen reaction occurs by initial nucleophilic addition of a cysteine -SH group on the enzyme to the keto group of the /3-ketoacyl CoA to yield an alkoxide ion intermediate. Cleavage of the C2-C3 bond then follows, with expulsion of an acetyl CoA enolate ion. Protonation of the enolate ion gives acetyl CoA, and the enzyme-bound acyl group undergoes nucleophilic acyl substitution by reaction with a molecule of coenzyme A. The chain-shortened acyl CoA that results then enters another round of tire /3-oxidation pathway for further degradation. 

Steps 1, 3 Phosphate transfers, steps 2, 5, 8 isomerizatlons step 4 retro-aldoi reaction step 5 oxidation and nucleophilic acyl substitution steps 7, 10 phosphate transfers step 9 F.2 dehydration... 

Certain CoA thioester using enzymes catalyze reactions at the fS-carbon or other carbons of the acyl group more distant from the thioester functionality. The fatty acid fi-oxidation cycle provides some examples (Fig. 3). Fatty acids 7 enter the cycle by initial conversion to the CoA ester 8, which is then oxidized to the a,P-unsaturated thioester 9 by a flavin-dependent enzyme. Addition of water to the double bond to form the fi-hydroxy thioester 10 is catalyzed by the enzyme crotonase, which is the centerpiece of the crotonase superfamily of enzymes that catalyze related reactions (37), which is followed by oxidation of the alcohol to form the fi-keto thioester 11. A retro-Claisen reaction catalyzed by thiolase forms acetyl-CoA 12 along with a new acyl-CoA 13 having a carbon chain two carbons shorter than in the initial or previous cycle. 

Steps 1, 3 phosphate transfers steps 2, 5, 8 i.somerizations step 4 retro-aldol reaction step 5 oxidation and nucleophilic acyl substitution steps 7, 10 phosphate transfers step 9 E2 dehydration Nucleophilic acyl substitution of acetyl dihydrolipoamide by coenzyme A Cl and C6 of glucose become -CH groups C3 and C4 become CO -Citrate and isocitrate E2 elimination of water, followed by conjugate addition (CH3)2CHCH2COCOr E2 reaction... 

Two new sesquiterpenoid metabolites, dihydroilludin M (186) and illudaceta-lic acid (187), have been isolated from Clitocybe illudens. Treatment of illudin S (188) with 40" sulphuric acid at 0°C gives the dimeric product (189) which is believed to arise by a retro-Prins reaction to generate formaldehyde and the acyl fulvene (190) followed by electrophilic recombination of the liberated formaldehyde and two molecules of the fulvene. ... 

Annulated pyridines have also been synthesized via a (4+2) cycloaddition strategy involving oxazole 6, which is made via a multicomponent coupling reaction in a single step <01OL877>. Acylation of 6 with a a,P-unsaturated acyl chloride is the first step in a domino reaction where an intramolecular Diels-Alder reaction is followed by a retro-Michael reaction (7-+8). 

Recently, an interesting strategy for in situ activation of primary aUyhc alcohols 68 as acetates in Pd-catalyzed allylations was described by Tunge and Grenning (Scheme 12.35) [69]. The acyl group required for activation is obtained by the retro-Claisen reaction of the pronucleophile with the highly basic primary allyl... 

Q Nucleophilic addition of coenzyme A to the keto group occurs, followed by a retro-Claisen condensation reaction. The products are acetyl CoA and a chain-shortened fatty acyl CoA. 

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