Stable attachment of the HMB-linker to continuous cellulose membranes for parallel solid phase spot synthesis

Tetrahedron Letters

Volumn 38, Issue 6, 1997, Pages 1029-1032

  Volkmer Engert, Rudolf ^a   Hoffmann, Berit ^a   Schneider Mergener, Jens ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

PEPTIDE;

ARTICLE; DRUG DESIGN; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; MASS SPECTROMETRY; MEMBRANE; METHODOLOGY; PEPTIDE SYNTHESIS;

EID: 0031562028     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)02508-7     Document Type: Article

References (19)

1. 1. Special abbreviations used: HMB: hydroxymethylbenzoic acid; MCPBA: 3-chloroperoxybenzoic acid; Phth: phthaloyl; Fmoc: 9-fluorenylmethoxycarbonyl-; TBTU: 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; DIEA: diisopropylethylamine; DIC: diisopropylcarbodiimide; TFA: trifluoroacetic acid; DCM: dichloromethane; NMI: N-methy-imidazole; HATU: O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate.
2. 2. Frank, R.; Doring, R. Tetrahedron, 1988, 44, 6031-6040.
3. 3. Frank, R. Tetrahedron, 1992, 48, 9217-9232.
4. 4. Kramer, A.; Volkmer-Engert, R.; Malin, R1; Reineke, U.; Schneider-Mergener, J. Peptide Res., 1993, 6, 314-319.
5. 5. Volkmer-Engert, R.; Ehrhard, B.; Hellwig, J.; Kramer, A.; Höhne, W.; Schneider-Mergener, J. Lett. Peptide Sci., 1994, 1, 243-253.
6. 6. Kramer, A.; Schuster, A.; Reineke, U.; Malin, R.; Volkmer-Engert, R.; Landgraf, C.; Schneider-Mergener, J. Methods (Comp. Meth. Enzymol.), 1994, 6, 388-395.
7. 7. Frank, R. J. Biotechnol., 1995, 41, 259-272.
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11. 2O-). MS (EI,150°C): m/z = 295 [M⊕].
12. 12. Synthetic procedure for 3: Whatman 50 paper (10 × 7 cm) was washed in a stainless steel dish with 20 ml 25% trifluoroacetic acid in dichloromethane for 20 min, 2 × 20 ml dichloromethane, 2 × 20 ml 10% triethylamine in dichloromethane, 2 × 20 ml dichloromethane, 2 × 20 ml tetrahydrofuran and dried over phosphorus pentoxide. In a closed stainless steel dish the dried paper sheet was soaked with a solution of 1 or 2 (6.1 mmol) and zinc chloride (8.8 mmol) in abs. tetrahydrofuran. After 24 h the membrane was washed with tetrahydrofuran, dimethylformamide and methanol. In case of the epoxide 1 the membrane was treated with a solution of 3.5 ml hydrazine hydrate (80%) in 40 ml ethanol for 24 h and washed with methanol, acetic acid, 10% triethylamine in dimethylformamide, dimethylformamide and methanol yielded in the modified cellulose membrane 3. In case of the epoxide 2 the membrane was treated with a solution of 20% piperidine in dimethylformamide for 15 min, washed with diethylformamide and methanol resulting in the modified membrane 3.
13. 13. Knorr, R.; Trzeciak, A.; Bannworth, W.; Gillessen, D. Tetrahedron Lett., 1989, 30, 1927-1930.
14. 14. Fields, G. B.; Noble, R. L. Int. J. Peptide Protein Res. 1990, 35, 161-214.
15. 15. The HMB derivative 4 was prepared by: (i) formation of the allylester derivative (ii) esterification of the hydroxyl function with Fmoc-glycine (DIC/NMI) (iii) cleavage of the allylester.
16. 16. Carpino, L. A. J. Am. Chem. Soc., 1993, 115, 4397-4398.
17. 17. Volkmer-Engert, R. Über die Darstellung heteromerer Peptide aus Aminosäuren und Uronsäure-Derivaten, Thesis, Freie Universität Berlin, 1991.
18. 18. Before treatment with ammonia vapour, the cellulose membrane was extensively washed with water, phosphate buffer (0. 1M, pH 7.5), water, methanol and dried.
19. 19. Malin, R.; Steinbrecher, R.; Jannsen, J.; Semmler, W.; Noll, B.; Johannsen, B.; Frömmel, C.; Höhne, W.; Schneider-Mergener, J. J. Am. Chem. Soc., 1995, 117, 11821-11821.