Synthesis of alkynyl amino acids and peptides and their palladium-catalyzed coupling to ferrocene

被引:40
作者
Brosch, O [1 ]
Weyhermüller, T [1 ]
Metzler-Nolte, N [1 ]
机构
[1] Max Planck Inst Strahlenchem, D-45470 Mulheim, Germany
关键词
D O I
10.1021/ic990256+
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
A method for attaching organometallics to the C-terminus of amino acids via a Pd-catalyzed two-step procedure is presented. Boc-protected enantiomerically pure amino acids 1 (a Phe, b Leu, c Met, d Ser) are reacted with 1,1-diethylpropargylamine to yield alkynyl amino acids 2. After reaction with (p-iodoanilido)ferrocene carboxylic acid 3 in the presence of 5 mol % PdCl2(PPh3)(2)/CuI ferrocene amino acids 4 are obtained in ca. 80% yield. The reaction does not require anhydrous conditions and tolerates functional groups such as amides, alcohols (Ser, 4d) or thioethers (Met, 4c). A complete characterization by multinuclear NMR (including N-15) is carried out. Cyclic voltammetry shows a reversible wave at about +190 mV (vs Fc/Fc(+)) independent of the nature of the attached amino acid. In the solid state, 2a forms a left-handed helix along the crystallographic c axis which is stabilized by hydrogen bonds as revealed by a single-crystal X-ray structure determination. A comparison of IR data in solution and the solid slate suggests that hydrogen bonding is also important for the solid-state structures of ferrocene amino acids 4 but does not play a role in solution. The use of this methodology for peptide chemistry is demonstrated by labeling the dipeptide Boc-Met-Phe-OH at the C-terminus and the tripeptide Boc-Phe-Glu-Leu-OMe with ferrocene. The alkyne anchoring group in the tripeptide is introduced at the Cy(Glu) atom at an early stage of the peptide synthesis and is not affected by subsequent deprotection and coupling reactions.
引用
收藏
页码:5308 / 5313
页数:6
相关论文
共 39 条
[1]   Transition-metal receptor systems for the selective recognition and sensing of anionic guest species [J].
Beer, PD .
ACCOUNTS OF CHEMICAL RESEARCH, 1998, 31 (02) :71-80
[2]  
BODANSZKY F, 1984, PRACTICE PEPTIDE SYN
[3]   Covalent attachment of an electroactive sulfydryl reagent in the active site of cytochrome P450cam as revealed by the crystal structure of the modified protein [J].
Di Gleria, K ;
Nickerson, DP ;
Hill, HAO ;
Wong, LL ;
Fülöp, V .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (01) :46-52
[4]  
Dibowski H, 1998, ANGEW CHEM INT EDIT, V37, P476, DOI 10.1002/(SICI)1521-3773(19980302)37:4<476::AID-ANIE476>3.0.CO
[5]  
2-2
[6]   DERIVATIZING REAGENTS BASED ON FERROCENE FOR HPLC-ECD DETERMINATION OF PEPTIDES AND PROTEINS [J].
ECKERT, H ;
KOLLER, M .
JOURNAL OF LIQUID CHROMATOGRAPHY, 1990, 13 (17) :3399-3414
[7]  
Eckert H., 1986, ANGEW CHEM, V98, P168
[8]   CONFORMATION-DIRECTING EFFECTS OF A SINGLE INTRAMOLECULAR AMIDE-AMIDE HYDROGEN-BOND - VARIABLE-TEMPERATURE NMR AND IR STUDIES ON A HOMOLOGOUS DIAMIDE SERIES [J].
GELLMAN, SH ;
DADO, GP ;
LIANG, GB ;
ADAMS, BR .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (04) :1164-1173
[9]   RADICAL REACTIONS IN AQUEOUS-SOLUTION - USE OF THE ACI-ANION OF NITROMETHANE AS A SPIN TRAP [J].
GILBERT, BC ;
NORMAN, ROC .
CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1982, 60 (12) :1379-1391
[10]   ETA(5)-PENTAMETHYLCYCLOPENTADIENYLRUTHENIUM(II) COMPLEXES CONTAINING ETA(6)-CO-ORDINATED DIPEPTIDES WITH AROMATIC SIDE-CHAINS [J].
GLEICHMANN, AJ ;
WOLFF, JM ;
SHELDRICK, WS .
JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS, 1995, (10) :1549-1554