Transesterification thioesters

Step 4 of Figure 29.12 Oxidative Decarboxylation The transformation of cr-ketoglutarate to succinyl CoA in step 4 is a multistep process just like the transformation of pyruvate to acetyl CoA that we saw in Figure 29.11. In both cases, an -keto acid loses C02 and is oxidized to a thioester in a series of steps catalyzed by a multienzynie dehydrogenase complex. As in the conversion of pyruvate to acetyl CoA, the reaction involves an initial nucleophilic addition reaction to a-ketoglutarate by thiamin diphosphate vlide, followed by decarboxylation, reaction with lipoamide, elimination of TPP vlide, and finally a transesterification of the dihydrolipoamide thioester with coenzyme A. 

Conversion of Free or Silylated Carboxylic Acids into Esters, Thioesters, Lactones, or Ketenes. Transesterification of Esters with Alcohols... 

Ester-thioester copolymers were enzymatically synthesized (Scheme 7). ° The lipase CA-catalyzed copolymerization of e-caprolactone with 11-mercaptoundecanoic acid or 3-mercaptopropionic acid under reduced pressure produced the polymer with molecular weight higher than 2 x 10". The thioester unit of the resulting polymer was lower than the feed ratio. The transesterification between poly(8-caprolactone) and 11-mercaptoundecanoic acid or 3-mercaptopropionic acid also took place by lipase CA catalyst. Recently, aliphatic polythioesters were synthesized by lipase CA-catalyzed polycondensation of diesters with 1,6-hexanedithiol. ... 

Transesterification from thioesters to esters188 or amides189,190 (lactams) are conducted by Cu1- or CuII-based Lewis acids (Scheme 45). Addition of alcohols to isocyanates is accelerated by CuCl.191... 

K. M. Knights, R. Gasser, W. Klemisch, In vitro Metabolism of Acitretin by Human Liver Microsomes Evidence for an Acitretinoyl-Coenzyme A Thioester Conjugate in the Transesterification to Etretinate , Biochem. Pharmacol. 2000, 60, 507-516. 

Transesterification of the resulting alkylated B-keto thioesters to the (orresponding oxo esters is readily achieved using alcohols under various iiM-tal catalysis. ... 

CALB-catalyzed copolymerization of CL with 11-mercaptoundecanoic acid (1IMU) leads to the formation of poly(ester-c6>-thioester)s having a Mn of 13.7 kDa (PDI 1.6) after precipitation [30] (Fig. 11). The amount of incorporated IIMU (8.7mol%) was slightly less than the feed ratio (10mol%). Similar results were obtained when using 3-mercaptopropionic acid (3MP) as a comonomer (Mn 14.3 kDa, PDI 1.4). CALB-catalyzed transesterification of pCL with either 1 IMU or 3MP resulted in similar H-NMR and C-NMR spectra as the direct copolymerization of the two monomers, showing that continuous transesterification plays an important role in the microstructure of the polymer [30]. 

Fig. 11 Copolymerization of CL with aliphatic co-mercapto carboxylic acids (top) and transesterification of pCL with aliphatic co-mercapto carboxylic acids (bottom) to give random copolymers with thioester linkages [30]...

The splicing mechanism, which is illustrated for this intein, is shown in the accompanying equations.1 1 Step a is an N —> S or N —> O acyl shift. This is followed by transesterification (step b) which involves either thioesters (as illustrated) or oxygen esters. Formation of a succinmide intermediate (step c) releases the intein and the spliced protein. The latter must undergo an S—> N or O—> N acyl shift (step d), and the succinimide in the extein must be hydrolyzed to complete the process. 

In the synthesis of a-amino acids [290] through addition of the carbanion of MMTS to nitriles the overall process involves three other steps frequently encountered in sulfur-mediated chemistry a Pummerer-type rearrangement, with a less common migration of a methylthio group, and a Raney nickel desulfurization following transesterification of the thioester function. 

The DKR hydrolysis of thioesters described previously has also been extended to transesterifications in toluene, using triethylamine and Candida antartica lipase.28 This general approach can therefore be applied to the resolution of a wide range of both water-soluble and water-insoluble thioesters by selecting an appropriate solvent, base, and enzyme system. 

In addition to thioesterifications employing the C-terminal condensation with alkyl-thiols, the Danishefsky group demonstrated an alternative type of thioesterification (Scheme 11.6) [74], A suitably side chain-protected peptide acid is condensed with an amino acid 2-dithioethyl phenyl ester. The 2-dithioethyl phenyl ester is prone to rearrangement to a thioester through O S transesterification under reducing (NCL) conditions. 

Copper Lewis acids have found many applications in the last decade in a variety of organic transformations and more notably in enantioselective reactions. In particular, Cu(OTf)2 and Cu(SbFg)2 in conjunction with chiral bisoxazolines are the chiral Lewis acids of choice for cycloadditions, aldol reactions, ene reactions, and other selective transformations. Moderately Lewis acidic copper salts are also reagents for transesterifications, dehydrations, and hydrolysis. The thiophilic nature of copper makes them ideal for selective deprotection of thio acetals and thioesters and offer practical advantages over mercury salts. 

The transesterification of 2-pyridylthioesters can be conducted in high yield with the aid of copper(I) or copper(II) Lewis acids [36]. The reaction is remarkable in that bulky alcohols react readily. The t-butyl ester 56 was prepared in high yield from 55 at room temperature with the aid of CuBr2, and the sterically encumbered ester 57 was likewise prepared in a similar 91 % yield (Sch. 15). The macrocycle 59 was obtained in an impressive yield from the thioester 58 [37]. Successful cyclization was highly... 

A promising new chemoselective ligation procedure has also been developed that utilizes a-azidoacyl peptides that are acylated by peptide thioesters under the Staudinger reduction conditions using 2-phosphanylbenzenethiol for transesterification of the thioester, trapping of the azido component as the phosphazene followed by intramolecular O N acyl shift (Scheme 78).t 5336,84i]... 

Transesterification has been carried out with phase-transfer catalysts, without an added solvent. Nonionic superbases (see p. 365) of the type P(RNCH2CH2)3N catalyze the transesterification of carboxylic acid esters at 25°C. ° Silyl esters (R C02SiR3) have been converted to alkyl esters (R C02R) via reaction with alkyl halides and tetrabutylammonium fluoride. Thioesters are converted to phenolic esters by treatment with triphosgene-pyridine and then phenol. 

Coenzyme A must now be added to the acetoacetate. The thioester bond is a high energy bond, so ATP equivalents must be used. In this case the energy comes from a transesterification of the CoAS from succinyl CoA to acetoacetate by Coenzyme A transferase (2). The succinyl CoA comes from the TCA cycle where a GTP is not made. 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

The synthesis starts with the thioester 64 to get the cis boron enolate 75 we need for the syn product Once the adduct 76 has been made, the sulfur has done its work and can be removed. Transesterification with MeOH and HgCl2 and straightforward steps lead to iodide 78. Once this iodide has reacted with the enolate of pentanone, there will be no trace of the carbonyl that originally allowed the aldol chemistry to be performed. 

Figure 9-15. Dynamic resolution in the hydrolysis/transesterification of thioesters.

Once a thioester with the appropriate number of carbon atoms is obtained, it undergoes a transesterification reaction with glycerol in order to form fats, oils, and phospholipids (Sections 26.3 and 26.4). 

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