Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis

An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed

Vers la synthèse du tricycle ABC du Taxol

During this thesis, we tried to apply the olefin metathesis reaction to the synthesis of the ABC tricycle of taxol, a natural molecule isolated in the 60' from the pacifican yew. We have studied to different retrosyntheses: - the first relies on relay ring closing metathesis to form the eight-membered B ring. - the second relies on an ene-yne-ene tandem metathesis to form the A and B cycles in one single step.Au cours de cette thèse, nous avons cherché à appliquer la réaction de métathèse des oléfines pour synthétiser le tricycle ABC du taxol, une molécule naturelle issue de l'if de l'ouest dans les années 1960. Nous avons pour cela étudié deux rétrosynthèses: - la première s'appuie sur la fermeture du cycle B à huit chaînons par une métathèse relais cyclisante. - la seconde repose sur une métathèse tandem ène-yne-ène permettant la formation en une seule étape des cycles A et B

Vers la synthèse du tricycle ABC du Taxol

PALAISEAU-Polytechnique (914772301) / SudocSudocFranceF

Relay ring-closing metathesis strategies towards the synthesis of the ABC tricycle of Taxol

Two synthetic routes towards the ABC tricycle of Taxol are presented. They both involve a relay ring-closing metathesis reaction to make the central B ring in a convergent fashion. In the first approach, the extender arm is positioned on the A ring, and the C ring bears the relay tether in the second route. Metathesis precursors with diverse extender arms were efficiently synthesised; unfortunately, the crucial metathesis reactions failed to deliver the target compounds in all cases

Synthesis of functionalized Morita–Baylis–Hillman adducts by a conjugate addition–elimination sequence

We have developed a new conjugate addition–elimination sequence for the diastereoselective synthesis of protected allylic syn 1,3-diols which are Morita–Baylis–Hillman adducts. The synthesis of the substrates involves a challenging cross-metathesis reaction that leads to hindered trisubstituted olefins