N-[Chloro(dimethylamino)methylene]-N-methylmethanaminium chloride (TMUCl Cl), the reagent of choice for the solid-phase synthesis of anilides

Tetrahedron Letters

Volumn 46, Issue 32, 2005, Pages 5383-5386

  Vendrell, Marc ^a   Ventura, Rubén ^a   Ewenson, Ariel ^b   Royo, Miriam ^a   Albericio, Fernando ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

^b Luxembourg Industries   (Israel)

Author keywords

Amide formation; Combinatorial chemistry; Coupling reagents; p Nitroanilide; Peptide synthesis

Indexed keywords

ANILIDE; CARBOXYLIC ACID; CHLORIDE; N [CHLORO(DIMETHYLAMINO)METHYLENE]N METHYLMETHANAMINIUM CHLORIDE; REAGENT; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION KINETICS; SOLID PHASE SYNTHESIS;

EID: 21844474310     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2005.05.140     Document Type: Article

References (31)

1. S.A. Kates F. Albericio Solid-Phase Synthesis. A Practical Guide 2000 Marcel Dekker New York (NY, USA)
2. I. Sucholeiki High-Throughput Synthesis 2001 Marcel Dekker New York (NY, USA)
3. P. Lloyd-Williams, F. Albericio, and E. Giralt Chemical Approaches to the Synthesis of Peptides and Proteins 1997 CRC Boca Raton (FL, USA)
4. G.B. Fields Methods in Enzymology Solid-Phase Peptide Synthesis Vol. 289 1997 Academic Press Orlando (FL, USA)
5. M. Goodman A. Felix L. Moroder C. Toniolo Houben-Weyl. Methods of Organic Chemistry Synthesis of Peptides and Peptidomimetics Vol. E22 2001 George Thieme Stuttgart (Germany)
6. T. Bruckdorfer, O. Marder, and F. Albericio Curr. Pharm. Biotech. 5 2004 29 43
7. F. Albericio Curr. Opin. Chem. Biol. 8 2004 211 221
8. F. Albericio, R. Chinchilla, D. Dodsworth, and C. Nájera Org. Prep. Proc. Int. 33 2001 203 303
9. M. El-Araby, H. Guo, R.S. Pottorf, and M.R. Player J. Comb. Chem. 6 2004 789 795
10. G. Quéléver, S. Burlet, C. Garino, N. Pietrancosta, Y. Laras, and J.-L. Kraus J. Comb. Chem. 6 2004 695 698
11. G. Giacomelli, A. Porcheddu, and M. Salaris Org. Lett. 5 2003 2715 2717
12. G. Luo, X. Li, and G.S. Poindexter Tetrahedron Lett. 43 2002 8909 8912
13. Z.J. Kaminski Biopolymers 55 2000 140 164
14. T. Isobe, and T. Ishikawa J. Org. Chem. 64 1999 6984 6988
15. L.A. Carpino, and A. El-Faham J. Am. Chem. Soc. 117 1995 5401 5402
16. J.F. McNamara, H. Lombardo, S. Pillai, I. Jensen, F. Albericio, and S.A. Kates J. Pept. Sci. 6 2000 512 518
17. A. El-Fayam, and M. Abdul-Ghani Org. Prep. Proced. Int. 35 2003 369 374
18. G.A. Strohmeier, W. Haas, and C.O. Kappe Chem. Eur. J. 10 2004 2919 2926
19. R. Vaidyanathan, V.G. Kalthod, D.P. Ngo, J.M. Manley, and S.P. Lapekas J. Org. Chem. 69 2004 2565 2568
20. N. Voyer, A. Lavoie, M. Pinette, and J. Bernier Tetrahedron Lett. 35 1994 355 358
21. F. Tonello, P. Ascenzi, and C. Montecucco J. Biol. Chem. 278 2003 40075
22. E. Zablotna, H. Dysasz, A. Lesner, A. Jáskiewicz, K. Kázmierczak, H. Miecznikowska, and K. Rolka Biochem. Biophys. Res. 319 2004 185 188
23. E.I. Milgotina, A.S. Shcheglov, G.B. Lapa, G.G. Chestukhina, and Tatiana L. Voyushina J. Pept. Res. 58 2001 12 16
24. Every experiment was carried out with 50 mg of Ac-Glu(OH)-Rink-PS-resin. Resins were swollen in DCM and the carboxylic acids were activated with CDI (25 equiv) in DMF or with TMUCl Cl (10 equiv) and DIEA (10 equiv) in DCM. Activation time varied from 20 to 30 min. Resins were filtered off and washed with DMF (5 × 1′) and DCM (5 × 1′). Afterwards, anilines (5 equiv) were solved in DCM-DMF (1:1) and added to the resin. Resins were under orbitalic shaking at room temperature for 2 or 16 h.
25. 18 (3.9 × 150 mm) 5 μm column with 996 PDA detection. Mass spectra were recorded on Micromass ZQ Mass Spectrometer.
26. M.P. Seiler, A.P. Stoll, A. Closse, W. Frick, A. Jaton, and J.-M. Vigouret J. Med. Chem. 29 1986 912 917
27. M. Cai, M. Stankova, S.J.K. Pond, A.V. Mayorov, J.W. Perry, H.I. Yamamura, D. Trivedi, and V.J. Hruby J. Am. Chem. Soc. 126 2004 7160 7161
28. G.-S. Jiao, L.H. Thoresen, and K. Burgess J. Am. Chem. Soc. 125 2003 14668 14669
29. S. Christoph, and F.-J. Meyer-Almes Biopolymers 72 2003 256 263
30. For nomenclature, see: J. Spengler, J.C. Jiménez, K. Burger, E. Giralt, and F. Albericio J. Pept. Res. 65 2005 550 555
31. In order to further separate the mixture of diastereomers from each peak, we analyzed the sample by chiral NP-HPLC using a Chiralpak AD column and a variety of elution solvents. Although the analysis by chiral NP-HPLC [hexane-ethanol-TFA (90:10:0.2)] of the starting material [±]-PPHT revealed two peaks in the same proportion, none of the assayed conditions were capable of separating the diastereomers expected in the final products.