Since 1986, a large number of oxazole- and thiazole-containing secondary metabolites have been isolated from cyanobacteria, nudibranch egg masses, ascidians, and sponges. The synthetically challenging structural variety of these heterocycles is only surpassed by their impressive range of biological activities, e.g. antifungal, antibiotic, cytotoxic, anthelminthic, tumor-promoting, antiviral, and analgesic properties. Generally, very little is known about the biological mode of action of marine natural products, and these compounds are not accessible in sufficient quantities for a thorough evaluation of their pharmacological potential. Synthetic chemistry occupies a unique role in marine biotechnology. Through the development of new methodology and total synthesis, natural products and analogs become accessible for SAR studies and tentative structure assignments can be verified or corrected. In a continuation of our program for the development of new methodology for heterocycle synthesis, the total synthesis of natural products, and structure-activity studies of biologically active agents, we plan to pursue the following goals: New synthetic methods for the preparation of five-membered heterocycles. Studies on the total synthesis, the secondary structure, and the metal-chelation properties of Lissoclinum-derived macrocyles. Investigations of biological relevance. Completion of the total synthesis of the complex polycyclic bisoxazole diazonamide A, a potent cytotoxic marine natural product. The proposed program represents a multi-dimensional effort to increase the basic knowledge of the function of marine natural products, establish new methods in heterocyclic chemistry, and identify novel pharmacophores.
|Wipf, Peter; Maciejewski, John P (2008) Titanocene(III)-catalyzed formation of indolines and azaindolines. Org Lett 10:4383-6|