Evaluation of monomethoxytrityl and dimethoxytrityl as orthogonal amino protecting groups in Fmoc solid phase peptide synthesis

Tetrahedron Letters

Volumn 39, Issue 13, 1998, Pages 1733-1734

  Matysiak, Stefan ^a   Böldicke, Thomas ^a   Tegge, Werner ^a   Frank, Ronald ^a  

^a Research Group for Molecular Recognition   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; AMINO ACID DERIVATIVE; PEPTIDE; TRITYL DERIVATIVE;

ARTICLE; CYCLIZATION; PEPTIDE SYNTHESIS; PROTEIN ASSEMBLY; PROTEIN MODIFICATION; SITE DIRECTED MUTAGENESIS; SOLID PHASE EXTRACTION;

EID: 0032568343     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00055-0     Document Type: Article

References (7)

1. 1. Aletras, A.; Barlos, K.; Gatos, D.; Koutsogianni, S.; Mamos, P. Int. J. Peptide Protein Res. 1995, 45, 488.
2. 2. Weiler, J. Development of New Methods for the Preparative Automated Oligonucleotide Synthesis, University of Konstanz, Germany 1995, p 93.
3. 3. 10.0 mmol of amino acid (side chain protected if applicable) was suspended in 20 mL of either abs. dimethylformamide/pyridine (1/1, v/v), Procedure A, or abs, dimethylformamide/dichloroethane (1/1, v/v) with 4.0 mL (24.45 mmol) of DIPEA added, Procedure B. To the stirred solution, 15 mmol of the corresponding tritylchloride derivative (Lancaster, UK) were added and the mixture was heated under reflux for 60-90 min. After cooling, 3 mL of methanol was added and the mixture was evaporated to an oil. This was diluted with 300 mL ethyl acetate and poured into 100 mL of saturated sodium bicarbonate solution. The organic layer was washed twice with 100 mL each of saturated sodium chloride. The combined aqueous layers were extracted twice more with ethyl acetate. The combined organic layers were dried with anhydrous sodium sulfate and evaporated. The product was purified by flash chromatography on 30 g silica gel with toluene/ethyl acetate/methanol (10/10/3 v/v containing 1% DIPEA) as solvent. Coevaporation of the product containing fractions with methanol and dichloromethane resulted in a colourless foam. Alternatively, the crude reaction product was dissolved in 50 ml of toluene and precipitated into 300 mL of petroleum ether under stirring. The suspension was cooled and the product collected as a colourless amorphous powder. The filtrate was evaporated and purified by chromatography as mentioned above to yield another fraction of the product. The products were dried in vacuo and stored at -20°C.
4. 3CN at a flow rate of 1 μL/min.
5. 5. This derivative has been reported recently for the synthesis of a dipeptide linker within a complex prodrug of an anticancer compound: Dubowchik, G.M.; Radia, S. Tetrahedron Lett. 1997, 38, 5257-5260.
6. 7) Peptide chains were assembled by coupling the respective Fmoc-amino acid derivatives with TBTU/N-methylmorpholine in dimethylformamide utilizing an AMS222 multiple synthesizer (ABIMED Analysen-Technik GmbH, Langenfeld, Germany) following the instructions of the manufacturer.
7. 7. Eichler, J.; Bienert, M.; Stierandová, A.; Lebl, M. Peptide Res. 1991, 4, 296-307.