Thioester bonds formation with

The mechanism of the C02 transfer reaction with acetyl CoA to give mal-onyl CoA is thought to involve C02 as the reactive species. One proposal is that loss of C02 is favored by hydrogen-bond formation between the A -carboxy-biotin carbonyl group and a nearby acidic site in the enzyme. Simultaneous deprotonation of acetyl CoA by a basic site in the enzyme gives a thioester eno-late ion that can react with C02 as it is formed (Figure 29.6). 

Formation of the internal thioester bond can be also accomplished by mixed anhydride assisted coupling of the N-protected peptide with a mercaptoacetylated C-terminal peptide fragment. 6 Sulfanylacids used for the preparation of peptide thioesters can be obtained from the common amino acids by the method of Pfister et al. 41 further described by Yan-keelov et al. 2 ... 

Thioesters have been used for carbon-carbon bond formation in transition metal-catalysed Grignard reactions. In the accompanying scheme two sequential cross-coupling reactions with 5-phenvl carbonochloridothioate and Grignard reagents led to a general and efficient ketone synthesis [377,378]. 

In a remarkable series of experiments, Baldwin and colleagues have studied peptide bond formation in the A. chrysogenum ACV synthetase [1,57,67-69], In the presence of glutamate, Cys, and Val, L-cysteinyl-D-valine is recovered exclusively. As has been stated above, glutamate does form an adenylate, but fails to be incorporated into peptides. The glutamate adenylate is thus not accessable for condensation to proceed at the first condensation domain. Presumably its presence, due to an induced conformational change [41], enhances peptide bond formation at the second condensation domain between the thioesters of Cys and Val, followed by epimerization of the dipeptidyl intermediate and hydrolytic release [reactions (12) and (13), with Cys for A2],... 

So far, the methods that have been shown to enable chemoselective peptide bond formation have relied upon the particular reactivity between thioesters and aminothiols. Almost simultaneously, Raines [36] and Bertozzi [37] reported a new method for the formation of a peptide bond with high chemoselectivity the so-called Staudinger ligation. This reaction had... 

In the first control point, citrate synthase catalyzes the condensation of acetyl-CoA with oxaloacetate to produce citrate (AG° = -32.2 kJ mol ). Although the reaction is reversible, the equilibrium lies very much in favor of citrate formation because of the hydrolysis of a bond in the intermediate compound, citroyl-CoA (Fig. 12-4). Citroyl-CoA is bound to citrate synthase, and the hydrolysis of the thioester bond, to produce citrate and coenzyme A, is an exergonic process. Citrate synthase is inhibited by its substrates (acetyl-CoA and oxaloacetate), and its activity is affected by... 

Acetal formation by the solvent occurs during the aminomethylation of isobutyr-aldehydc (see 8, 9 in Sec. A.l), and a transestcrification accompanies the reaction of dithiobutyric esters with methylolamine ethers (Fig. 59). Thus, Mannich bases 172, in which the thioester bond has been converted into O-ester bond, are obtained in good yields.- ... 

Optically active 1,2-diol units are often observed in nature as carbohydrates, macrolides or polyethers, etc. Several excellent asymmetric dihydroxylation reactions of olefins using osmium tetroxide with chiral ligands have been developed to give the optically active 1,2-diol units with high enantioselectivities. However, there still remain some problems, for example, preparation of the optically active anti-1,2-diols and so on. The asymmetric aldol reaction of an enol silyl ether derived from a-benzyloxy thioester with aldehydes was developed in order to introduce two hydroxyl groups simultaneously with stereoselective carbon-carbon bond formation by using the chiral tin(II) Lewis acid. For example, various optically active anti-a,p-dihydroxy thioester derivatives are obtained in good yields with excellent diastereo-... 

Recognition of the value of active esters for peptide bond formation emerged from work with vinyl esters ly cyanomethyl esters 5-phenyl thioesters 9,P1 piperidino esters 10, 3-pyridyl esters 4-nitrophenyl esters 12 2,4,6-trichlorophenyl esters,and phthalimido esters 17.t l Many activating moieties have surfaced over the years but only a limited number have survived the test of time and are in use today. These include 4-nitrophenyl 12,M 2,4,5-trichlorophenyl pentachlorophenyl pentafluorophenyl succininoido... 

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