Thioesters synthesis

How could this problem be solved Only traces of thioesters are formed from free carboxylic acid and thiols in aqueous solution, i.e., the equilibrium reaction 7.15 is shifted to the left. According to de Duve (1991), there are two possibilities for spontaneous thioester synthesis under conditions present on the primeval Earth ... 

According to equation 7.15, at higher temperatures and low pH values (around pH 2). As already stated, Weber (1984) was able to carry out a thioester synthesis starting from glycerinealdehyde and A-acetylcysteine. 

J. R. Cashman, C. E. Berkman, G. Underiner, C. A. Kolly, A. D. Hunter, Cocaine Benzoyl Thioester Synthesis, Kinetics of Base Hydrolysis, and Application to the Assay of Cocaine Esterases , Chem. Res. Toxicol. 1998, 11, 895-901. 

Coleman, T.M. and Huang, F. (2002) RNA-catalyzed thioester synthesis, Chem. Biol. 9, 1227-1236. 

Lamberet, G., Auberger, B., Bergere, J.L. 1997. Aptitude of cheese bacteria for volatile 5-methyl thioester synthesis. II. Comparison of coryneform bacteria, Micrococcaceae and some lactic acid bacteria starters. Appl. Microbiol. Biotechnol. 48, 393-397. 

Well-defined nickel-sulfur complexes that enable a stepwise combination of CO, alkyl, and thiol groups to give thioesters can be anticipated to yield deeper insight into the molecular mechanism of the acetyl-CoA synthesis (142, 149). The complex [Ni(C3Me2—S4)] afforded an example for such a thioester synthesis. In principle, it is even catalytic and Scheme 36 summarizes the individual steps (10). 

Weber AL. Prebiotic amino acid thioester synthesis thiol-dependent amino acid synthesis from formose substrates (formaldehyde and glycolaldehyde) and ammonia. Orig. Life Evol. Biosph. 1998 28 259-270. 

Development of Fmoc SPPS compatible thioester synthesis is important since several posttranslation modifications such as phosphorylation and glycosylation are most efficient with Fmoc SPPS. 

C-terminal peptide a-thioester, mUdly activated peptide ester acting as a valuable key intermediate for the synthesis/semi-synthesis of polypeptides and proteins by both chemical ligation and the Aimoto thioester approach. The synthesis of the peptide a-thioester (—r thioester) can be performed by standard SPPS using Boc- or Fmoc-based chemistry or, for larger target polypeptides, by application of intein-based bacterial expression systems. Peptide a-thioester synthesis can also be carried out based on an N-S acyl shift reaction mediated by a thiol ligation auxiliary [F. B. Perler, E. Adams, Curr. Opin. Biotechnol. 2000, 377 D. Swinnen, D. Hilvert, Org. Lett. 2000, 2, 2439 R. Quaderer, D. Hilvert, Org. Lett. 2001, 3, 3181 T. W. Muir, Annu. Rev. Biochem. 2003, 72, 249 T. Kawakami et al.. Tetrahedron Lett. 2005, 46, 8805 J. A. Camarero, A. R. Mitchell, Prot. Pept. Lett. 2005, 12, 723]. 

Peptide Thioester Synthesis via Intramolecular Af to S Acyl Shift. 115... 

Peptide Thioester Synthesis via Intramolecular iV to 5 Acyl Shift... 

Scheme 6 Strategy for peptide thioester synthesis by intramolecular NS acyl shift on sulfonamide linker...

The Fmoc SPPS procedure can be used in peptide thioester synthesis based on intramolecular N-S acyl shift reactions. One of advantages of using Fmoc SPPS is that post-translationally modified peptides, i.e., phosphorylated, glycosylated peptides can be produced. Post-translational modifications play major roles in the regulation of numerous biological processes. 

Kang J, Macmillan D (2010) Peptide and protein thioester synthesis via JV- S acyl transfer. Org Biomol Chem 8 1993-2002... 

Ackrill T, Anderson DW, Macmillan D (2010) Towards biomolecular assembly employing extended native chemical ligation in combination with thioester synthesis using an N— S acyl shift. Biopolymers 94 495-503... 

Premdjee B, Adams AL, Macmillan D (2011) Native A-glycopeptide thioester synthesis through N— S acyl transfer. Bioorg Med Chem Lett 21 4973 975... 

The final process for coenzyme A thioester synthesis is by the thiolytic cleavage of /8-keto acyl coen me A derivatives. The thiolase reaction is the principal metabolic process for degrading the hydrocarbon chain of fatty acids. 

The reaction has been extended to amide and thioester synthesis [119] ... 

General Synthesis and Reactions of Esters Synthesis of Diesters Synthesis of Hydroxy-esters Synthesis of Keto-esters Synthesis of Unsaturated Esters Synthesis of Aromatic Esters Synthesis of Thioesters Synthesis of Vinylogous Esters... 

Synthesis.—The so-called push-pull acetylenes [e.g. (157)], already mentioned in connection with thioester synthesis, can also be utilized as acyl transfer reagents in a general method for the formation of amide bonds between carboxylic acids and amines (Scheme 49). The overall, one-pot sequence gives excellent yields and appears to be very simple to perform. The isolable intermediates are usually clean and crystalline, and when it is used in dipeptide syntheses little racemization occurs. As mentioned earlier, the carboxylic acid component may contain unprotected alcohol, amino-, and mercapto-groups. 

In the following section, two strategies for peptide thioester synthesis will be described (1) the safety-catch linker (SCL) strategy and (2) the backbone amide linker (BAL) strategy using tri-thioortho ester building blocks. 

Nakamura K, Mori H, Kawakami T, Hojo H, Nakahara Y, Aimoto S (2007) Peptide thioester synthesis via an auxiliary-mediated N-S Acyl shift reaction in solution. Int J Pept Res Ther 13 191-202... 

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