ABSHAProject reference: 220410
Funded under :
A biomimetic synthesis of Haouamine A and analogues
Total cost:EUR 169 390,93
EU contribution:EUR 169 390,93
Coordinated in:United Kingdom
Topic(s):PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development"
Call for proposal:FP7-PEOPLE-2007-2-1-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
"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--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."
WC1E 6BT LONDON