Acid mediated formation of an N-acyliminium ion from tubulysins: A new methodology for the synthesis of natural tubulysins and their analogs

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 22, 2011, Pages 6778-6781

  Vlahov, Iontcho R ^a   Wang, Yu ^a   Vetzel, Marilynn ^a   Hahn, Spencer ^a   Kleindl, Paul J ^a   Reddy, Joseph A ^a   Leamon, Christopher P ^a  

^a Endocyte Inc   (United States)

Author keywords

C C bond formation; N,N Diacyl aminals; N Acyl N,O acetals; N Acyl N,S thioacetals; N Acyliminium ion; Tubulysin

Indexed keywords

ACETAL DERIVATIVE; ACETIC ACID; ALCOHOL; CARBON; CYTOTOXIC AGENT; ION; N ACYLIMINIUM ION; NITRILE; THIOL DERIVATIVE; TRIFLUOROACETIC ACID; TUBULYSIN; TUBULYSIN A; TUBULYSIN B; TUBULYSIN C; TUBULYSIN G; TUBULYSIN I; UNCLASSIFIED DRUG;

ARTICLE; BATCH FERMENTATION; CELL STRAIN KB; CHEMICAL BOND;

ACETIC ACID; BIOLOGICAL AGENTS; CHEMISTRY TECHNIQUES, SYNTHETIC; IMINES; IONS; MYXOCOCCALES; OLIGOPEPTIDES; PIPECOLIC ACIDS; TUBULIN MODULATORS;

EID: 80054722829     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.09.041     Document Type: Article

References (25)

1. F. Sasse, H. Steinmetz, G. Höfle, and H. Reichenbach J. Antibiot. 53 2000 879
2. H. Steinmetz, N. Glasser, E. Herdtweck, F. Sasse, H. Reichenbach, and G. Höfle Angew. Chem., Int. Ed. 43 2004 4888 Angew. Chem., Int. Ed. 2004, 116, 4996
3. M. Khalil, F. Sasse, H. Lünsdorf, Y. Elnakady, and H. Reichenbach Chem. Bio. Chem. 7 2006 678
4. G. Kaur, M. Hollingshead, S. Holbeck, Schauer-Vikašinović, R. Camalier, A. Dömling, and S. Agarwal Biochem. J. 396 2006 235
5. For a review on tubulysins see: A. Dömling, and W. Richter Mol. Diversity 9 2005 141 and references therein
6. G. Höfle, N. Glaser, T. Leibold, U. Karama, F. Sasse, and H. Steinmetz Pure Appl. Chem. 75 2003 167
7. G. Friestad, J.C. Marié, and A. Deveau Org. Lett. 6 2004 3249
8. P. Wipf, T. Takada, and M. Rishel Org. Lett. 6 2004 4057
9. P. Wipf, and Z. Wang Org. Lett. 9 2007 1605
10. H.M. Peltier, J.P. McMahon, A.W. Patterson, and J.A. Ellman J. Am. Chem. Soc. 128 2006 16018
11. A. Patterson, H. Peltier, F. Sasse, and J. Ellman Chem. Eur. J. 13 2007 9534
12. Z. Wang, P. McPherson, B. Raccor, R. Balachandran, G. Zhu, B. Day, A. Vogt, and P. Wipf Chem. Biol. Drug Des. 70 2007 75
13. M. Sani, G. Fossati, F. Huguenot, and M. Zanda Angew. Chem., Int. Ed. 46 2007 3526 Agnew. Chem., Int. Ed. 2007, 119, 3596
14. A. Patterson, H. Peltier, and J. Ellman J. Org. Chem. 73 2008 4362
15. A. Dömling, B. Beck, U. Eichelberger, S. Sakamuri, S. Menon, Q.Z. Chen, Y. Lu, and L. Wessjohann Angew. Chem., Int. Ed. 45 2006 7235 reported the total synthesis of natural tubulysins U and V but actually a correction stated that epimeric compounds were synthesized: Angew. Chem., Int. Ed. 2007, 46, 2337
16. O. Pando, S. Dörner, R. Preusentanz, A. Denkert, A. Porzel, W. Richter, and L. Wessjohann Org. Lett. 11 2009 5567
17. T. Shibue, T. Hirai, I. Okamoto, N. Morita, H. Masu, I. Azumaya, and O. Tamura Chem. Eur. J. 16 2010 11678
18. For excellent reviews on chemistry of N-acyliminium ions and their application see the contributions of one of the pioneers in the field W. Nico Speckamp: W.N. Speckamp, and M. Moolenaar Tetrahedron 56 2000 3817
19. W.N. Speckamp, and H. Hiemstra Ibid 41 1985 4367
20. H. De Koning, M. Moolenaar, H. Hiemstra, and W.N. Speckamp Atta-ur-Rahman Studies in Natural Products Chemistry Vol. 13 1993 Elsevier Amsterdam 473 518
21. H. Hiemstra, and W.N. Speckamp B. Trost, I. Fleming, Comprehensive Organic Synthesis Vol. 2 1991 Pergamon Oxford 1047 1082
22. H. Hiemstra, and W.N. Speckamp A. Brossi, The Alkaloids Vol. 32 1988 Academic Oxford 271 339 See also
23. M. Petrini, and E. Torregiani Synthesis 2 2007 159
24. E. Vilsmaier, and R. Bayer Synthesis 1 1976 46
25. 4 (20 μL) in isovaleronitrile (150 μL). After stirring at room temperature for 22 h, the reaction was quenched with 2.0 mM sodium phosphate buffer (pH 7.0, 15 mL) and purified by HPLC to give 16 mg of 5 (64% yield w/w) as a white solid.