HBTU (2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, Hexafluorophosphate Benzotriazole Tetramethyl Uronium) is a couplingreagent used in solid phase peptide synthesis. It was introduced in 1978 and shows resistance against racemization.[2][3] It is used because of its mild activating properties.[4]
The product obtained by reaction of HOBt with tetramethyl chloro uronium salt (TMUCl) was assigned to a uronium type structure, presumably by analogy with the corresponding phosphonium salts, which bear a positive carbon atom instead of the phosphonium residue. Later, it was shown by X-ray analysis that salts crystallize as aminium rather than the corresponding uronium salts.[5][6]
Mechanism
This scheme depicts the general mechanistic steps of HBTU creating an activated ester out of the carboxylate anion of the acid substrate. The deprotination of the carboxylic acid and the aminolysis of the activated ester are not shown.
HBTU activates carboxylic acids by forming a stabilized HOBt (Hydroxybenzotriazole) leaving group. The activated intermediate species attacked by the amine during aminolysis is the HOBt ester.
To create the HOBt ester, the carboxyl group of the acid attacks the imide carbonyl carbon of HBTU. Subsequently, the displaced anionic benzotriazole N-oxide attacks of the acid carbonyl, giving the tetramethyl urea byproduct and the activated ester. Aminolysis displaces the benzotriazole N-oxide to form the desired amide.[7]
^Dourtoglou, Vassilis. (April 1978). "L'hexafluorophosphate de O-benzotriazolyl-N,N-tetramethyluronium: Un reactif de couplage peptidique nouveau et efficace". Tetrahedron Letters. 19 (15): 1269–1272. doi:10.1016/0040-4039(78)80103-8.
^Knorr, R.; Trzeciak, A.; Bannwarth, W.; Gillessen, D. (1989). "New coupling reagents in peptide chemistry". Tetrahedron Letters. 30 (15): 1927–1930. doi:10.1016/S0040-4039(00)99616-3.
^Solange, A. (1992). "HBTU: a mild activating agent of muramic acid". Bioorganic & Medicinal Chemistry Letters. 2 (6): 571–574. doi:10.1016/S0960-894X(01)81199-9.
^Carpino, L.; Imazumi, H.; El-Faham, A.; Ferrer, F.; Zhang, C.; Lee, Y.; Foxman, B.; Henklein, P.; Hanay, C.; Mügge, C.; Wenschuh, H.; Klose, J.; Beyermann, M.; Bienert, M. (2002). "The uronium/guanidinium peptide coupling reagents: Finally the true uronium salts". Angewandte Chemie International Edition. 41 (3): 441–445. doi:10.1002/1521-3773(20020201)41:3<441::AID-ANIE441>3.0.CO;2-N. PMID 12491372.
^Abdelmoty, I.; Albericio, F.; Carpino, L.; Foxman, B.; Kates, S. (1994). "Structural studies of reagents for peptide bond formation: Crystal and molecular structures of HBTU and HATU". Letters in Peptide Science. 1 (2): 57–67. doi:10.1007/BF00126274. S2CID 38746650.
^Bradley, Mark; Valeur, Eric (2009-01-26). "Amide bond formation: beyond the myth of coupling reagents". Chemical Society Reviews. 38 (2): 606–631. doi:10.1039/B701677H. ISSN 1460-4744. PMID 19169468.
January 17, 2023
hbtu, benzotriazol, tetramethyluronium, hexafluorophosphate, hexafluorophosphate, benzotriazole, tetramethyl, uronium, coupling, reagent, used, solid, phase, peptide, synthesis, introduced, 1978, shows, resistance, against, racemization, used, because, mild, a. HBTU 2 1H benzotriazol 1 yl 1 1 3 3 tetramethyluronium hexafluorophosphate Hexafluorophosphate Benzotriazole Tetramethyl Uronium is a coupling reagent used in solid phase peptide synthesis It was introduced in 1978 and shows resistance against racemization 2 3 It is used because of its mild activating properties 4 HBTU NamesIUPAC name 3 Bis dimethylamino methyliumyl 3H benzotriazol 1 oxide hexafluorophosphateOther names HBTUIdentifiersCAS Number 94790 37 1 Y3D model JSmol Interactive imageChemSpider 2014894 YECHA InfoCard 100 133 815EC Number 619 076 7PubChem CID 2733084UNII X5I03TZQ8D YCompTox Dashboard EPA DTXSID00915302InChI InChI 1S C11H16N5O F6P c1 14 2 11 15 3 4 17 16 10 8 6 5 7 9 10 12 13 16 1 7 2 3 4 5 6 h5 8H 1 4H3 q 1 1Key UQYZFNUUOSSNKT UHFFFAOYSA NSMILES CN C C N C C ON1C2 CC CC C2N N1 F P F F F F FPropertiesChemical formula C 11H 16F 6N 5O PMolar mass 379 247 g mol 1Appearance White crystalsMelting point 200 C 392 F 473 K Hazards 1 Occupational safety and health OHS OSH Main hazards IrritantGHS labelling PictogramsSignal word WarningHazard statements H315 H319 H335Precautionary statements P210 P240 P241 P261 P264 P271 P280 P302 P352 P304 P340 P305 P351 P338 P312 P332 P313 P337 P313 P362 P370 P378 P403 P233 P405 P501Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references The product obtained by reaction of HOBt with tetramethyl chloro uronium salt TMUCl was assigned to a uronium type structure presumably by analogy with the corresponding phosphonium salts which bear a positive carbon atom instead of the phosphonium residue Later it was shown by X ray analysis that salts crystallize as aminium rather than the corresponding uronium salts 5 6 Mechanism Edit This scheme depicts the general mechanistic steps of HBTU creating an activated ester out of the carboxylate anion of the acid substrate The deprotination of the carboxylic acid and the aminolysis of the activated ester are not shown HBTU activates carboxylic acids by forming a stabilized HOBt Hydroxybenzotriazole leaving group The activated intermediate species attacked by the amine during aminolysis is the HOBt ester To create the HOBt ester the carboxyl group of the acid attacks the imide carbonyl carbon of HBTU Subsequently the displaced anionic benzotriazole N oxide attacks of the acid carbonyl giving the tetramethyl urea byproduct and the activated ester Aminolysis displaces the benzotriazole N oxide to form the desired amide 7 See also EditEDC HATU BOP reagent PyBOP PyAOP reagentReferences Edit 2 1h Benzotriazole 1 yl 1 1 3 3 tetramethyluronium hexafluorophosphate pubchem ncbi nlm nih gov Dourtoglou Vassilis April 1978 L hexafluorophosphate de O benzotriazolyl N N tetramethyluronium Un reactif de couplage peptidique nouveau et efficace Tetrahedron Letters 19 15 1269 1272 doi 10 1016 0040 4039 78 80103 8 Knorr R Trzeciak A Bannwarth W Gillessen D 1989 New coupling reagents in peptide chemistry Tetrahedron Letters 30 15 1927 1930 doi 10 1016 S0040 4039 00 99616 3 Solange A 1992 HBTU a mild activating agent of muramic acid Bioorganic amp Medicinal Chemistry Letters 2 6 571 574 doi 10 1016 S0960 894X 01 81199 9 Carpino L Imazumi H El Faham A Ferrer F Zhang C Lee Y Foxman B Henklein P Hanay C Mugge C Wenschuh H Klose J Beyermann M Bienert M 2002 The uronium guanidinium peptide coupling reagents Finally the true uronium salts Angewandte Chemie International Edition 41 3 441 445 doi 10 1002 1521 3773 20020201 41 3 lt 441 AID ANIE441 gt 3 0 CO 2 N PMID 12491372 Abdelmoty I Albericio F Carpino L Foxman B Kates S 1994 Structural studies of reagents for peptide bond formation Crystal and molecular structures of HBTU and HATU Letters in Peptide Science 1 2 57 67 doi 10 1007 BF00126274 S2CID 38746650 Bradley Mark Valeur Eric 2009 01 26 Amide bond formation beyond the myth of coupling reagents Chemical Society Reviews 38 2 606 631 doi 10 1039 B701677H ISSN 1460 4744 PMID 19169468 Retrieved from https en wikipedia org w index php title HBTU amp oldid 1082331816, wikipedia, wiki, book, books, library,
