- Improved procedure for the synthesis of thiazolium-type peptide coupling reagents: BMTB as a new efficient reagent
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An efficient scalable synthesis of 2-halothiazolium-type peptide coupling reagents has been developed. The key step is the formation of the 2-bromothiazole scaffold through cyclization of α-thiocyanato ketones with hydrogen bromide. Using this method, the new coupling reagent 2-bromo-N-methylthiazolium bromide (BMTB) was synthesized. BMTB was tested in a difficult model coupling reaction of two sterically hindered N-methylated amino acids and showed higher activity than the well-established peptide coupling reagent HATU.
- Wischnat, Ralf,Rudolph, Joachim,Hanke, Roman,Kaese, Roger,May, Achim,Theis, Heidi,Zuther, Undine
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p. 4393 - 4394
(2007/10/03)
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- Condensation reagents and a process for their preparation
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The present invention relates to new bromo- and chlorothiazolium salts of the formula (I) in which R1, R2, R3, R4, n and X? have the meaning indicated in the disclosure, a process for their preparation, their use as condensation reagents, particularly as peptide coupling reagents, and intermediates for the preparation of these compounds.
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- A novel thiazolium type peptide coupling reagent for hindered amino acids
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A highly efficient coupling reagent, 2-bromo-3-ethyl-4-methyl thiazolium tetrafluoroborate (BEMT), was designed, synthesized and successfully applied to the synthesis of oligopeptides containing N-alkyl or α-C-dialkyl amino acids. Its efficiency was evaluated by HPLC and 1H NMR methods, and demonstrated by synthesis of a number of N-methyl-rich peptide segments with good yields and negligible racemization. The mechanism of coupling was studied by HPLC, 1H NMR and IR monitoring; it is proposed that labile (acyloxy)thiazolium salts and N-protected amino acid bromides were the major active intermediates with concomitant formation of N-ethyl-4-methyl thiazolidones and a small amount of oxazolones and N-protected amino acid anhydrides.
- Li, Peng,Jie, Cheng Xu
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p. 8301 - 8304
(2007/10/03)
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