COMU: A Safer and More Effective Replacement for Benzotriazole-Based Uronium Coupling Reagents

被引：255

作者：

El-Faham, Ayman ^{[1
,2
,3
]}

Subiros Funosas, Ramon ^{[1
,4
]}

Prohens, Rafel ^{[5
]}

Albericio, Fernando ^{[1
,4
,6
]}

机构：

[1] Inst Biomed Res, Barcelona 08028, Spain

[2] King Saud Univ, Dept Chem, Coll Sci, Riyadh 11451, Saudi Arabia

[3] Univ Alexandria, Dept Chem, Fac Sci, Alexandria 21321, Egypt

[4] Networking Ctr Bioengn Biomat & Nanomed, CIBER BBN, Barcelona 08028, Spain

[5] Univ Barcelona, Plataforma Polimorfisme & Calorimetria Serv Cient, E-08028 Barcelona, Spain

[6] Univ Barcelona, Dept Organ Chem, E-08028 Barcelona, Spain

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2009年 / 15卷 / 37期

关键词：

coupling reagents; Oxyma; peptides; solid-phase synthesis; uronium salts; PEPTIDE-SYNTHESIS; HEXAFLUOROPHOSPHATE; 1-HYDROXY-7-AZABENZOTRIAZOLE; EFFICIENCY; SALTS;

D O I：

10.1002/chem.200900615

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We describe a new family of uronium-type coupling reagents that differ in their iminium moieties and leaving groups. The presence of the morpholino group in conjunction with an oxime derivative-especially ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma)-had a marked influence on the solubilities, stabilities, and reactivities of the reagents. Finally, the new uronium salt derived from Oxyma (COMU) performed extremely well in the presence of only 1 equiv of base, thereby confirming the effect of the hydrogen bond acceptor in the reaction. COMU also showed a less hazardous safety profile than the benzotriazole-based HDMA and HDMB, which exhibited unpredictable autocatalytic decompositions. Furthermore, the Oxyma moiety contained in COMU suggests a lower risk of explosion than in the case of the benzotriazole derivatives.

引用

页码：9404 / 9416

页数：13

共 52 条

[1]

Abdelmoty Iman, 1994, Letters in Peptide Science, V1, P57, DOI 10.1007/BF00126274

[2]

Albericio F, 1997, METHOD ENZYMOL, V289, P104

[3] 2-mercaptopyridine-1-oxide-based peptide coupling reagents [J].

Albericio, F ;

Bailén, MA ;

Chinchilla, R ;

Dodsworth, DJ ;

Nájera, C .

TETRAHEDRON, 2001, 57 (47) :9607-9613

[4]

Albericio F, 2001, ORG PREP PROCED INT, V33, P205

[5] Use of onium salt-based coupling reagents in peptide synthesis [J].

Albericio, F ;

Bofill, JM ;

El-Faham, A ;

Kates, SA .

JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (26) :9678-9683

[6] Methods and Protocols of modern solid phase peptide synthesis [J].

Amblard, M ;

Fehrentz, JA ;

Martinez, J ;

Subra, G .

MOLECULAR BIOTECHNOLOGY, 2006, 33 (03) :239-254

[7] 2-mercaptopyridone 1-oxide-based uronium salts:: New peptide coupling reagents [J].

Bailén, MA ;

Chinchilla, R ;

Dodsworth, DJ ;

Nájera, C .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (24) :8936-8939

[8]

Barton J., 1997, CHEM REACTION HAZARD, V2nd

[9]

Breipohl G, 1991, Ger. Offen., Patent No. [DE 90-4016596, 904016596]

[10]

Carpino L. A., 2002, ANGEW CHEM, V114, P457, DOI DOI 10.1002/1521-3757(20020201)

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