Since 1986, a considerable number of oxazole-containing marine metabolites have been isolated from nudibranch egg masses 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. Partly due to the structural complexity and the novel heterocyclic systems of many of these compounds, however, relatively little synthetic work has been done. Especially, no approaches toward the recently isolated hennoxazoles or thiangazole has been reported. Both of these compounds show very impressive antiviral activities. Thiangazole shows a one hundred percent inhibition of HIV-1 (HTLV-IIIB) infection at 4.7 pM with no cell toxicity at 4.7 mM concentration. Additionally it discriminates between HIV- and HIV-2 Strains. Hennoxazole A was reported to be active against herpes simplex virus type 1 (lC500.6mug/ml). The proposed research program will achieve the following goals: Development of a general synthetic methodology for the preparation of functionalized polyoxazoles/thiazolines. Total syntheses of thiangazole and hennoxazole A. Concomitantly, the relative configuration at the C(8) and C(22) stereocenters as well as the absolute configuration of hennoxazoles will be determined At a later stage of this project, we plan to study the metal binding properties of thiangazole and hennoxazole A and its analogues, and to correlate these properties to the biological activities of these compounds.
|Wipf, Peter; Maciejewski, John P (2008) Titanocene(III)-catalyzed formation of indolines and azaindolines. Org Lett 10:4383-6|