Peptide synthesis beyond DMF: THF and ACN as excellent and friendlier alternatives

被引：77

作者：

Jad, Yahya E. ^{[1
]}

Acosta, Gerardo A. ^{[2
,3
]}

Khattab, Sherine N. ^{[4
]}

de la Torre, Beatriz G. ^{[1
,5
]}

Govender, Thavendran ^{[1
]}

Kruger, Hendrik G. ^{[1
]}

El-Faham, Ayman ^{[4
,6
]}

Albericio, Fernando ^{[1
,2
,3
,5
,6
,7
,8
]}

机构：

[1] Univ Kwazulu Natal, Sch Hlth Sci, Catalysis & Peptide Res Unit, ZA-4001 Durban, South Africa

[2] Inst Res Biomed Barcelona, Barcelona 08028, Spain

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

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

[5] Yachay City Knowledge, Yachay Tech, Sch Chem, Urcuqui 100119, Ecuador

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

[7] Univ Kwazulu Natal, Sch Chem & Phys, ZA-4001 Durban, South Africa

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

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2015年 / 13卷 / 08期

基金：

新加坡国家研究基金会;

关键词：

AMIDE BOND FORMATION; COUPLING REAGENTS; MEDICINAL CHEMISTRY; RACEMIZATION; OXYMA; DICHLOROMETHANE; COMBINATORIAL; REPLACEMENT; IMMONIUM; SOLVENT;

D O I：

10.1039/c4ob02046d

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

To date, DMF has been considered as the only solvent suitable for peptide synthesis. Here we demonstrate the capacity of THF and ACN, which are friendlier solvents than DMF, to yield the product in higher purity than DMF. Using various peptide models, both THF and ACN reduced racemization in solution-phase and solid-phase synthesis when compared with DMF. Moreover, the use of ACN and THF in the solid-phase peptide synthesis of hindered peptides, such as Aib-enkephalin pentapeptide and Aib-ACP decapeptide, in combination with a complete polyethylene glycol resin (ChemMatrix), gave a better coupling efficiency than DMF.

引用

页码：2393 / 2398

页数：6

共 39 条

[1] Solid-phase peptide synthesis using acetonitrile as a solvent in combination with PEG-based resins [J].

Acosta, Gerardo A. ;

del Fresno, Montserrat ;

Paradis-Bas, Marta ;

Rigau-DeLlobet, Maria ;

Cote, Simon ;

Royo, Miriam ;

Albericio, Fernando .

JOURNAL OF PEPTIDE SCIENCE, 2009, 15 (10) :629-633

[2]

Albericio F, 1997, METHOD ENZYMOL, V289, P104

[3] Green chemistry tools to influence a medicinal chemistry and research chemistry based organisation [J].

Alfonsi, Kim ;

Colberg, Juan ;

Dunn, Peter J. ;

Fevig, Thomas ;

Jennings, Sandra ;

Johnson, Timothy A. ;

Kleine, H. Peter ;

Knight, Craig ;

Nagy, Mark A. ;

Perry, David A. ;

Stefaniak, Mark .

GREEN CHEMISTRY, 2008, 10 (01) :31-36

[4] From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future [J].

Bruckdorfer, T ;

Marder, O ;

Albericio, F .

CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 2004, 5 (01) :29-43

[5] Analysis of the reactions used for the preparation of drug candidate molecules [J].

Carey, John S. ;

Laffan, David ;

Thomson, Colin ;

Williams, Mike T. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2006, 4 (12) :2337-2347

[6] Complex polyfluoride additives in Fmoc-amino acid fluoride coupling processes. Enhanced reactivity and avoidance of stereomutation [J].

Carpino, LA ;

Ionescu, D ;

El-Faham, A ;

Beyermann, M ;

Henklein, P ;

Hanay, C ;

Wenschuh, H ;

Bienert, M .

ORGANIC LETTERS, 2003, 5 (07) :975-977

[7] 1-HYDROXY-7-AZABENZOTRIAZOLE - AN EFFICIENT PEPTIDE COUPLING ADDITIVE [J].

CARPINO, LA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (10) :4397-4398

[8] Fast conventional Fmoc solid-phase peptide synthesis: a comparative study of different activators [J].

Chantell, Christina Ann ;

Onaiyekan, Michael Abayomi ;

Menakuru, Mahendra .

JOURNAL OF PEPTIDE SCIENCE, 2012, 18 (02) :88-91

[9] K-Oxyma: a Strong Acylation-Promoting, 2-CTC Resin-Friendly Coupling Additive [J].

Cherkupally, Prabhakar ;

Acosta, Gerardo A. ;

Nieto-Rodriguez, Lidia ;

Spengler, Jan ;

Rodriguez, Hortensia ;

Khattab, Sherine N. ;

El-Faham, Ayman ;

Shamis, Marina ;

Luxembourg, Yoav ;

Prohens, Rafel ;

Subiros-Funosas, Ramon ;

Albericio, Fernando .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2013, 2013 (28) :6372-6378

[10] High-Efficiency Solid Phase Peptide Synthesis (HE-SPPS) [J].

Collins, Jonathan M. ;

Porter, Keith A. ;

Singh, Sandeep K. ;

Vanier, Grace S. .

ORGANIC LETTERS, 2014, 16 (03) :940-943

← 1 2 3 4 →