Peptide coupling in the presence of highly hindered tertiary amines

被引:85
作者
Carpino, LA
Ionescu, D
El-Faham, A
机构
[1] Department of Chemistry, Box 34510, University of Massachusetts, Amherst
[2] Department of Organic Chemistry, Faculty of Chemistry, University of Bucharest
[3] Department of Chemistry, Faculty of Science, Alexandria University, Alexandria
关键词
D O I
10.1021/jo950912x
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Previously, 2,4,6-trimethylpyridine (collidine), due to steric shielding around the N-atom, was found to be an efficient base for effecting peptide segment coupling via azabenzotriazole-based onium-style coupling reagents. A number of even more highly hindered bases, including 2,3,5,6-tetramethylpyridine , 2, 6-di-tert-butyl-4-(dimethylamino)pyridine, triisopropylamine, and N-tert-butylmorpholine, have been compared with collidine in such reactions. Some of the newer bases showed advantages in terms of convenience in handling and maintenance of configuration during segment coupling processes, although dramatic differences based on steric effects were not observed. On the basis of results with a number of test peptides and many base-coupling reagent combinations, it was noted that most efficient results are obtained if 1 equiv of HOAt is present as an additive during the coupling process. For rapid activation of onium-style coupling reagents during stepwise solid-phase coupling reactions, the stronger base 2,6-di-tert-butyl-4-(dimethylamino)pyridine was more effective than collidine.
引用
收藏
页码:2460 / 2465
页数:6
相关论文
共 48 条
[11]   STRUCTURES OF STERICALLY OVERCROWDED AND CHARGE-PERTURBED MOLECULES .5. GAS-PHASE STRUCTURES OF FLATTENED AMINES .4. TRIISOPROPYLAMINE - A STERICALLY OVERCROWDED MOLECULE WITH A FLATTENED NC3 PYRAMID AND A P-TYPE NITROGEN ELECTRON PAIR [J].
BOCK, H ;
GOEBEL, I ;
HAVLAS, Z ;
LIEDLE, S ;
OBERHAMMER, H .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1991, 30 (02) :187-190
[12]   EQUILIBRIUM ACIDITIES IN DIMETHYL-SULFOXIDE SOLUTION [J].
BORDWELL, FG .
ACCOUNTS OF CHEMICAL RESEARCH, 1988, 21 (12) :456-463
[13]   EQUILIBRIA INVOLVING ORGANIC-ANIONS IN DIMETHYLSULFOXIDE AND N-METHYLPYRROLIDIN-2-ONE - ACIDITIES, ION-PAIRING, AND HYDROGEN-BONDING [J].
BORDWELL, FG ;
BRANCA, JC ;
HUGHES, DL ;
OLMSTEAD, WN .
JOURNAL OF ORGANIC CHEMISTRY, 1980, 45 (16) :3305-3313
[14]   PREPARATION AND REACTIONS OF 2,6-DI-T-BUTYLPYRIDINE AND RELATED HINDERED BASES . A CASE OF STERIC HINDRANCE TOWARD PROTON [J].
BROWN, HC ;
KANNER, B .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1966, 88 (05) :986-&
[15]   DESICCANT EFFICIENCY IN SOLVENT DRYING .3. DIPOLAR APROTIC-SOLVENTS [J].
BURFIELD, DR ;
SMITHERS, RH .
JOURNAL OF ORGANIC CHEMISTRY, 1978, 43 (20) :3966-3968
[16]   EFFECT OF TERTIARY BASES ON O-BENZOTRIAZOLYLURONIUM SALT-INDUCED PEPTIDE SEGMENT COUPLING [J].
CARPINO, LA ;
EL-FAHAM, A .
JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (04) :695-698
[17]   TETRAMETHYLFLUOROFORMAMIDINIUM HEXAFLUOROPHOSPHATE - A RAPID-ACTING PEPTIDE COUPLING REAGENT FOR SOLUTION AND SOLID-PHASE PEPTIDE-SYNTHESIS [J].
CARPINO, LA ;
EL-FAHAM, A .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (19) :5401-5402
[18]   EFFICIENCY IN PEPTIDE COUPLING - 1-HYDROXY-7-AZABENZOTRIAZOLE VS 3,4-DIHYDRO-3-HYDROXY-4-OXO-1,2,3-BENZOTRIAZINE [J].
CARPINO, LA ;
EL-FAHAM, A ;
ALBERICIO, F .
JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (11) :3561-3564
[19]   ADVANTAGEOUS APPLICATIONS OF AZABENZOTRIAZOLE (TRIAZOLOPYRIDINE)-BASED COUPLING REAGENTS TO SOLID-PHASE PEPTIDE-SYNTHESIS [J].
CARPINO, LA ;
EL-FAHAM, A ;
MINOR, CA ;
ALBERICIO, F .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1994, (02) :201-203
[20]   1-HYDROXY-7-AZABENZOTRIAZOLE - AN EFFICIENT PEPTIDE COUPLING ADDITIVE [J].
CARPINO, LA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (10) :4397-4398