A Versatile Synthesis of 3-Substituted
4-Cyano-1,2,3,4-tetrahydro-1-oxo-β-carbolines

Kilian Huber; Oliver Kast; Franz Bracher

doi:10.1055/s-0030-1258282

PAPER

A Versatile Synthesis of 3-Substituted 4-Cyano-1,2,3,4-tetrahydro-1-oxo-β-carbolines

Kilian Huber, Oliver Kast, Franz Bracher*
Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians University Munich, Butenandtstrasse 5-13, 81377 Munich, Germany
Fax: +49(89)218077171; e-Mail: franz.bracher@cup.uni-muenchen.de;

Abstract

All articles of this category

Abstract

In a project aimed at the synthesis of analogues of the cytotoxic β-carboline alkaloid bauerine C with more advantageous solubility properties, a 3-amino analogue was prepared by treating ethyl 3-(cyanomethyl)indole-2-carboxylate with ammonia. Upon addition of aldehydes or ketones to the reaction mixture, 3-substituted 4-cyano-1,2,3,4-tetrahydro-1-oxo-β-carbolines were obtained in a one-pot condensation. When cyclic ketones are used, the procedure allows a convenient synthesis of tetracyclic spiro compounds.

Key words

β-carbolines - cyclizations - multicomponent reactions - indoles - lactams

Full Text

References

1 Newman DJ. Cragg GM. J. Nat. Prod. 2007, 70: 461

2 Larsen LK. Moore RE. Patterson GM. J. Nat. Prod. 1994, 57: 419

3 Pohl B. Luchterhandt T. Bracher F. Synth. Commun. 2007, 37: 1273

4 Huber K. Bracher F. Z. Naturforsch., B: Chem. Sci. 2007, 62: 1313

5 Huber K. Schemies J. Uciechowska U. Wagner JM. Rumpf T. Lewrick F. Süss R. Sippl W. Jung M. Bracher F. J. Med. Chem. 2010, 53: 1383

6a Wang S. Dong Y. Wang X. Hu X. Liu JO. Hu Y. Org. Biomol. Chem. 2005, 3: 911

6b Cincinelli R. Cassinelli G. Dallavalle S. Lanzi C. Merlini L. Botta M. Tuccinardi T. Martinelli A. Penco S. Zunino F. J. Med. Chem. 2008, 51: 7777

6c Wu J.-P. Wang J. Abeywardane A. Andersen D. Emmanuel M. Gautschi E. Goldberg DR. Kashem MA. Lukas S. Mao W. Martin L. Morwick T. Moss N. Pargellis C. Patel UR. Patnaude L. Peet GW. Skow D. Snow RJ. Ward Y. Werneburg B. White A. Bioorg. Med. Chem. Lett. 2007, 17: 4664

7a Bracher F. Hildebrand D. Pharmazie 1993, 48: 695

7b Bracher F. Hildebrand D. Häberlein H. Nat. Prod. Res. 2004, 18: 391

7c For a very recent application of this methodology, see: La Ferla B. Orsato A. Zona C. Cervi G. Papeo G. Felder ER. Nicotra F. Synthesis 2010, 601

8a Liu C. Widenhoefer RA. J. Am. Chem. Soc. 2004, 126: 10250

8b Liu C. Han X. Wang X. Widenhoefer RA. J. Am. Chem. Soc. 2004, 126: 3700

9 Barker AJ, Kettle JG, and Faull AW. inventors; WO 9,907,351. Preparation of substituted indoles for treatment of a disease or condition mediated by monocyte chemoattractant protein-1 (MCP-1):

10 Kozikowski AP. Ishida H. Heterocycles 1980, 14: 55

11 Snyder HR. Smith CW. Stewart JM. J. Am. Chem. Soc. 1944, 66: 200

12a Schneller SW. Luo JK. Hosmane RS. De Clercq E. Stoeckler JD. Agarwal KC. Parks RE. Saunders PP. J. Med. Chem. 1984, 27: 1737

12b Schneller SW. Luo JK. Hosmane RS. Duerrfeld RH. J. Heterocycl. Chem. 1984, 21: 1153

13 Monge A. Palop JA. Goñi T. Martinez A. Fernández-Alvarez E. J. Heterocycl. Chem. 1984, 21: 381