L'hexafluorophosphate de O-benzotriazolyl-N,N-tetramethyluronium: Un reactif de couplage peptidique nouveau et efficace

Dourtoglou, Vassilis; Ziegler, Jean-Claude; Gross, Bernard

doi:10.1016/0040-4039(78)80103-8

Cited by 187 publications

(98 citation statements)

References 8 publications

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“…[7] Thus, starting with Boc-Ile-OH (4), dicyclohexylcarbodiimide coupling [8] with allylamine gave amide 5 in 95 % yield. Deprotection under acidic conditions followed by direct HBTU coupling [9] with Boc-Phe-OH gave the dipeptide 6 in 73 % yield. Further deprotection and peptide coupling subsequently gave the tripeptide 7 in 71 % yield.…”

Section: Resultsmentioning

confidence: 99%

Ring‐Closing Metathesis in the Synthesis of Biologically Active Peptidomimetics of Apicidin A

et al. 2007

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Syntheses of novel 16-membered macrocyclic peptidomimetics are reported, which employ iterative peptide coupling followed by high yielding ring-closing metathesis (RCM) as the key cyclization step. The target macrocyclic compounds include examples containing a (2S)-amino-8-oxodecanoic acid (Aoda) residue as analogues of apicidin A, a known potent histone deacetylase (HDAC) inhibitor. These showed modest levels of biological activity as HDAC inhibitors.

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Section: Resultsmentioning

confidence: 99%

Ring‐Closing Metathesis in the Synthesis of Biologically Active Peptidomimetics of Apicidin A

et al. 2007

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“…Synthetic scheme for preparing TOMBU (17) and COMBU (18). Carpino et al [28] reported that HBTU (4) and HATU (5) exist in the N-form (guanidinium salt) instead of the O-form (uronium salt) and that the two forms can easily be distinguished by means of 13 C-NMR spectroscopy. The carbocationic carbon of the N-form appears at 151-152 ppm while that of the O-form appears at 161-162 ppm [29,30].…”

Section: Preparation Of Tombu and Combumentioning

confidence: 99%

“…In addition, they had a lower risk of explosion than that of benzotriazole derivatives [20][21][22][23][24]. More recently, in 2010, a new family of uronium salts [HTMU (13), HMMU (14), and HDmPyMU (15)] based on isonitroso Meldrum's acid (HONM, 12) was reported as stand-alone coupling reagents [25] (Figure 2). HONM (12) shows structural similarities to OxymaPure (10), except that it has a special orientation of the carbonyl moiety and can therefore play an assisted basic catalytic role during the coupling reaction.…”

Section: Introductionmentioning

confidence: 99%

“…However, the need for stronger activating reagents led to the replacement of carbodiimides with stand-alone coupling reagents (such as aminium/uronium and phosphonium ones). Aminium salts, such as HBTU (4), [12,13] HATU (5), [14,15] and HCTU (6), [16] are probably the most widely used and the most powerful examples. [17] Aminium salts 4-6 bear a tetramethyl moiety on their carbocation skeletons, and additives 1-3 are utilized as leaving groups for 4-6, respectively.…”

Section: Introductionmentioning

confidence: 99%

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TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B

et al. 2014

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Abstract:Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis, we reveal that they show better performance than OPEN ACCESSMolecules 2014, 19 18954 HBTU in terms of preserving chiral integrity and coupling yields, but slightly worse performance than COMU.

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“…Preventing the loss of configuration is one of the major challenges in peptide synthesis. [4][5][6][7][8] The activation of carboxylic acids using phosphonium 9-13) and uranium salts [14][15][16][17] is a fast, reliable process. These salts are prepared from a phosphonium or uronium cation bonded generally to a XO-group, normally a hydroxylamine derivative.…”

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confidence: 99%

Sulfonate Esters of 1-Hydroxypyridin-2(1H)-one and Ethyl 2-Cyano-2-(hydroxyimino)acetate (Oxyma) as Effective Peptide Coupling Reagents to Replace 1-Hydroxybenzotriazole and 1-Hydroxy-7-azabenzotriazole

Khattab

2010

Chem. Pharm. Bull.

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The activation of carboxylic acids for the formation of amides or esters is an important process usually carried out using the so-called peptide coupling reagents. 1-3) This is followed by the reaction with the amine moiety of another amino acid to produce the desired peptide. The effective formation of a peptide bond not only depends on the reaction rate and yield but also on the suppression of the undesired racemization and other side reactions and thus minimizes the loss of the optical integrity at the chiral center of the carboxylic component. Preventing the loss of configuration is one of the major challenges in peptide synthesis. [4][5][6][7][8] The activation of carboxylic acids using phosphonium 9-13) and uranium salts [14][15][16][17] is a fast, reliable process. These salts are prepared from a phosphonium or uronium cation bonded generally to a XO-group, normally a hydroxylamine derivative. These salts combine the functions of activating agents with suppressing additives and were successfully introduced in peptide synthesis. 18) A common method of minimizing the loss of configuration during stepwise coupling in solution phase is to add an additive such as 1-hydroxy-benzotriazole (HOBt) to the coupling mixture. 19) Recently, 1-hydroxy-7-azabenzotriazole (HOAt) and its derived phophonium or uronium/guanidinuim salts have been described as favorable coupling additives or reagents for both solution 20) and solidphase synthesis. 21) HOAt has been reported to be more efficient than HOBt because of an anchimeric assistance effect caused by the pyridine ring. 22,23) These compounds enhance coupling yields and reduce the loss of chiral integrity during stepwise coupling.Esters of sulfonic acids and HOBt have been used for peptide coupling. [24][25][26][27][28] The reactivity of these sulfonate esters was shown to be directly related to the presence of electronwithdrawing substituents in both the HOBt and the sulfonic acid moieties. [29][30][31][32][33][34] This methodology has few applications, as the coupling process depends on the basicity and reactivity of the amino component. The use of such sulfonate esters for in situ coupling was often accompanied by the formation of a sulfonamide byproduct. 24,30) Such byproduct formation can be avoided by preactivation of the reactive carboxylic acid component.On the other hand, the use of a preactivation step is counterproductive, since the loss of configuration at the C-terminal carboxylic acid residue directly increases with preactivation time. 35) The replacement of HOBt by HOAt was expected to reduce the extent of configurational loss, but, on the contrary, the advantages of HOAt were lost during long preactivation times. 33,34) Oxyma (ethyl 2-cyano-2-(hydroxyimino)acetate) 4 has been tested as an additive for use in the carbodiimide approach for the formation of peptide bonds. It showed better performance than the classical HOBt and HOAt, which have recently been reported to exhibit explosive properties. Oxyma displayed a remarkable capacity to inhibit racemizati...

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L'hexafluorophosphate de O-benzotriazolyl-N,N-tetramethyluronium: Un reactif de couplage peptidique nouveau et efficace

Cited by 187 publications

References 8 publications

Ring‐Closing Metathesis in the Synthesis of Biologically Active Peptidomimetics of Apicidin A

Ring‐Closing Metathesis in the Synthesis of Biologically Active Peptidomimetics of Apicidin A

TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B

Sulfonate Esters of 1-Hydroxypyridin-2(1H)-one and Ethyl 2-Cyano-2-(hydroxyimino)acetate (Oxyma) as Effective Peptide Coupling Reagents to Replace 1-Hydroxybenzotriazole and 1-Hydroxy-7-azabenzotriazole

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