Efforts towards the total synthesis of brevenal and development of olefinic amide and olefinic lactam cyclizations using a reduced titanium alkylidene

Brevenal and its dimethyl acetal were isolated from laboratory cultures of the dinoflagellate Karenia brevis by Barden and co-workers in 2005. Brevenal has the potential to serve as therapeutic agents for the treatment of brevetoxins poisoning because of their low toxicity and ability to block the effect of brevetoxins in vivo. This dissertation describes our efforts towards the total synthesis of brevenal. A Cglycoside/metathesis approach is used in our synthesis. Of note is the generation of ?-C-glycosides in one pot by using a DMDO oxidation and zinc mediated C-C bond formation sequence. Lewis acid TBSOTf is very important in these reactions. Nucleophiles prefer to add from the axial position regardless of the epoxides. Cyclic enamides are valuable in their own and interesting precursors to a variety of natural products containing nitrogen. Although the olefinic-amide cyclizations would be synthetically useful, there are few reports of related cyclization that employ amides. Described here is the use of a reduced Titanium alkylidene reagent to effect one-step olefinic-amide and olefinic-lactam cyclizations.