Research objectives and content
The project will involve the development of new methods for the construction of the medium-ring cyclic ether units found in the brevetoxins and related marine natural products. Catalytic ring-closing metathesis reactions will be used to accomplish ring closure, providing 6- to 8-membered cyclic allyl ethers or enol ethers in high yield. The functionalistion of these cyclic ethers a their elaboration to bicyclic and tricyclic sub-units the brevetoxins will also be explored.
Training content (objective, benefit and expected impact)
The project will provide experience of several state-of-the-art synthetic methods. In particular, the use of metal alkylidene complexes for catalytic ring-ctosing metathesis reactions, and the application of carbenoid insertion reactions to organ synthesis. The project will involve the preparation and use of air-sensitive metal complexes and will provide experience of techniques that are normally restricted to organometallic chemistry.
Links with industry / industrial relevance (22)
Ring-closing metathesis has attracted an unprecedented amount of interest in recent years and seems destined to become the most generally applicable reaction for ring construction in organic synthesis. The work outlined above will demonstrate value of metathesis reactions for the efficient construction of rings. In addition, this work will allow the preparation of unnatural brevetoxin analogues which may possess interesting biological properties and permit the mode of action of the brevetoxins to be elucidated.
Much of the brevetoxin work already performed in Dr. Clark's group has been industrially funded.