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A biomimetic synthesis of Haouamine A and analogues

Objective

Haouamines A and B were isolated in 2003 by Zubia and co-workers from the Ascidian Aplidium haouarianum, collected off the coast of southern Spain. Haouamine A was found to exhibit selective cytotoxicity against a human colon cancer cell line (HT-29, IC50 = 0.1 µgml-1, 200nM). From a structural standpoint, these novel polycyclic alkaloid metabolites exhibit several fascinating features: both alkaloids feature an indeno tetrahydropyrimidine moiety that contains a diaryl quaternary center and anti-Bredt double bond. The tetrahydropyridine ring is fused to a highly strained 11-membered cyclophane ring system. In addition, NMR studies have shown that they exist in solution as a dynamic 2:1 interconverting mixture of stereoisomers generated either by nitrogen inversion or by atropisomerism of the biaryl unit. Of even greater import, the uniquely strained nature of the 3-aza-[7]-paracyclophane unit has been clearly revealed by X-Ray crystallography and the non-planar south-eastern aromatic ring is in fact so deformed that it exists in a boatlike conformation. The combination of interesting biological activity and novel chemical structure makes the haouamines attractive targets for synthesis.

Field of science

  • /natural sciences/earth and related environmental sciences/geology/mineralogy/crystallography
  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/clinical medicine/oncology/cancer/colorectal cancer

Call for proposal

FP7-PEOPLE-2007-2-1-IEF
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Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

University College London
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 169 390,93
Administrative Contact
Greta Borg-Carbott (Ms.)