HBTU

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HBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexauorophosphate), a coupling reagent commonly used in solid phase peptide synthesis. After being introduced in 1978, this agent shows popularity in chemistry and industry use due to its mild activating properties. Moreover, it also shows resistance against racemization. Low tendency for racemization is a key requirement for peptide synthesis. Especially for solid phase peptide synthesis, quantitative yields with short reaction times are crucial in order to make the synthesis of large peptides feasible. [1]

In vitro: Peptide synthesis relied mostly on efficient and safe coupling reagents. HBTU was proved to transform carboxylic acids into azides efficiently and practically. The process might be applied to a wide range of carboxylic acids including N-protected amino acids. In addition, HBTU was of great value in one-pot synthesis of dipeptidyl urea esters, ureas, and carbamates from acids. The advantages of HBTU included the following points: 1) Non-explosive and therefore more suitable for solution/solid phase peptide synthesis. 2) High solubility and stability in classical solvents. 3) Feasible for colorimetric reaction monitoring. [2]

In vivo: So far, no in vivo data has been reported.

Clinical trial: So far, no clinical trial has been conducted.

References:
[1]Adam S.  HBTU: a mild activating ageiw of muramic acid. Bioorg Med Chem Lett. 1992 Mar; 2(6): 571-4.
[2]Knorr R, Trzeciak A, Bannwarth W and Gillessen D.  New coupling reagents in peptide chemistry. Tetrahedron Lett. 1989; 30(15): 1927-30.

HBTU mediated 1-hydroxybenzotriazole (HOBt) conjugate addition: synthesis and stereochemical analysis of beta-benzotriazole N-oxide substituted gamma-amino acids and hybrid peptides.[Pubmed:25228027]

Org Biomol Chem. 2014 Nov 14;12(42):8462-72.

HBTU is a standard coupling agent commonly used for the activation of free carboxylic acids during the solution and solid phase peptide synthesis. 1-Hydroxybenzotriazole (HOBt) plays a significant role in reducing the racemization during peptide synthesis; hence it is regularly used as a coupling additive. Here, we are reporting the mild and facile conjugate addition of HOBt to E-vinylogous gamma-amino acids mediated by the HBTU. The reaction is moderately diastereoselective and novel beta-benzotriazole N-oxide (beta-BtO) substituted gamma-amino acids were isolated in moderate to good yields. The single crystal analysis of methyl esters of major (anti) and minor (syn) conjugate addition products infers the formation of exclusively N-alkylated benzotriazole N-oxides instead of O-alkylation of HOBt. In addition, we showed the utilization of beta-BtO substituted gamma-amino acids in peptide synthesis and studied their conformations in single crystals.

New and simple synthesis of acid azides, ureas and carbamates from carboxylic acids: application of peptide coupling agents EDC and HBTU.[Pubmed:20135041]

Org Biomol Chem. 2010 Feb 21;8(4):835-40.

Conversion of carboxylic acids into acid azides using peptide coupling agents, EDC and HBTU is described. The procedure is efficient, practical and applicable to a diverse range of carboxylic acids including N-protected amino acids. Using the same reagents, one-pot synthesis of ureas, dipeptidyl urea esters and carbamates from acids has also been achieved.

Anaphylaxis and allergic contact urticaria from occupational airborne exposure to HBTU.[Pubmed:16861336]

Occup Med (Lond). 2006 Sep;56(6):430-3.

We describe a case of anaphylaxis and allergic contact urticaria from occupational airborne exposure to HBTU (o-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate), which is a chemical used widely for solid and solution-phase peptide synthesis. Previously, the use of this chemical has been associated with occupational asthma, allergic contact urticaria and allergic contact dermatitis in individual cases, but not with anaphylaxis. Our diagnoses were based on the clinical symptoms, positive skin prick test (SPT) and positive skin provocation test to HBTU. The positive SPT indicates that the anaphylaxis reaction was IgE-mediated. We recommend that in the handling of HBTU, appropriate safety measures should be compulsory, and if work-related symptoms develop, the possibility of anaphylaxis should be considered in advising on appropriate work tasks.