Studies Toward the Total Synthesis of Tetrahydrofuran-Containing Natural Products

Natural products have played a significant role as leads and inspiration for many novel therapeutics. Among the most common structural fragments found in biologically active natural products is the tetrahydrofuran, a five membered oxygen-containing heterocycle. As oftentimes very little natural product is available from the producing organism, there has been a longstanding interest in the development of efficient and general synthetic methods to access tetrahydrofurans and tetrahydrofuran-containing natural products. This thesis summarizes recent efforts directed towards the total synthesis of amphirionin-4 and biselide A, two tetrahydrofuran-containing natural products with potentially useful biological activities. Amphirionin-4 is a polyketide isolated from Amphidinium sp. dinoflagellates, and has demonstrated potent proliferation activity in ST-2 stem cells. Biselide A is a marine macrolide isolated from the Okinawan ascidian Didemnidae sp., and has demonstrated potent cytotoxicity towards a variety of human cancer cell lines. Notably, the unifying element in our synthetic approaches to both of these natural products is a reliance on chlorohydrin-based strategies to access the tetrahydrofuran cores in an efficient, diastereoselective and enantioselective manner.