HBTU

Chemical properties

white to light yellow powder

The Uses of HBTU

HBTU is a coupling reagent used in peptide synthesis. HBTU has been shown to effectively suppress racemization.

The Uses of HBTU

peptide coupling reagent that reduces racemization

The Uses of HBTU

Peptide coupling reagent which suppresses racemization.

Biological Activity

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]

Preparation

To a suspension of the amine (3.0 g, 11.4 mmol), the acid (2.88 g, 9.54 mmol), and TEA (4.81 mL, 34.5 mmol) in DMSO (30 mL) was added HBTU (4.34 g, 34.5 mmol). The reaction mixture was stirred at RT for 18 h, after which time it was diluted with EtOAc (100 mL), washed with H2O (100 mL), brine (3 x 100 mL), dried (Na2SO4), and concentrated to a brown solid. The resulting material was triturated in MTBE then EtOAc to provide the product. [3.97 g, 7.8 mmol]

Purification Methods

Wash the salt with H2O (3x), CH2Cl2 (3x), dry and recrystallise it from MeCN. Dry it in a vacuum and store it cold in the dark [Dourtoglou et al. Tetrahedron Lett 1269 1978, NMR: Dourtoglou and Gross Synthesis 572 1984]. Benzoxazolinone (2 -hydroxybenzoxazole) [59 -49 -4] M 135.1, m 137 -139o, 142 -143o(corrected), b 121-213o/17mm, 335-337o/760mm. Benzoxazolinone is purified by recrystallisation from aqueous Me2CO followed by distillation at atmospheric pressure, then in a vacuum. The methyl mercury salt recrystallises from aqueous EtOH and has m 156-158o. [Bywater et al. J Am Chem Soc 67 905 1945, Beilstein 27 III/IV 2677.]

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.