Mad for Madangamines

Madangamines are a small group of complex pentacyclic alkaloids isolated from marine sponges of the order Haplosclerida, biogenetically derived from partially reduced bis-3-alkylpyridine macrocycles. Madangamine A, isolated from Xestospongia ingens by Andersen and co-workers in 1994 [1] was the first example of this new class of pentacyclic alkaloids and showed significant in vitro cytotoxicity against a number of cancer cell lines. Soon afterwards, four new members of this group, madangamines B–E, were isolated from the same sponge [2] and more recently madangamine F, also showing cytotoxic activity, has been isolated from the marine sponge Pachychalina alcaloidifera [3].

For the first time, the diazatricyclic core common to all madangamines has been enantioselectively assembled by M. Amat, J. Bosch and colleagues from the University of Barcelona, Spain. This represents a significant breakthrough in the total synthesis of these natural products. The key steps involve a stereoselective conjugate addition, ring-closing metathesis, stereoselective generation of the C–9 stereocenter, and closure of the piperidine A ring by aminohydroxylation.

• First Enantioselective Synthesis of the Diazatricyclic Core of Madangamine Alkaloids
  M. Amat, M. Pérez, S. Proto, T. Gatti, J. Bosch,
  Chem. Eur. J. 2010, 16 (32).
  DOI: 10.1002/chem.201000421

References

[1] F. Kong, R. J. Andersen, T. M. Allen, J. Am. Chem. Soc. 1994, 116, 6007—6008. DOI: 10.1021/ja00092a077
[2] F. Kong, E. I. Graziani, R. J. Andersen, J. Nat. Prod. 1998, 61, 267—271. DOI: 10.1021/np970458n
[3] J. H. H. L. De Oliveira, A. M. Nascimento, M. H. Kossuga, B. C. Cavalcanti, C. O. Pessoa, M. O. Moraes, M. L. Macedo, A. G. Ferreira, E. Hajdu, U. S. Pinheiro, R. G. S. Berlinck, J. Nat. Prod. 2007, 70, 538—543. DOI: 10.1021/np060450q