UC Irvine

The first chapter of this thesis focuses on the development of the competing enantioselective conversion method (CEC) for the assignment of the absolute configuration of amines. This method utilizes Bode’s hydroxamic esters as the source of chirality. The optimization and control studies for this method are discussed in detail. Many examples, including complex drugs and natural products, are examined and a preliminary mnemonic was developed.

The second chapter focuses on the efforts toward the synthesis of the western fragment of phainanoid F. Background is given on the previous failed routes in our laboratory and how they led to the new synthetic route. Three different approaches toward the fragment are discussed, one which failed, and the other two that are not yet complete. If efforts are placed in these approaches, it seems likely that one will afford the western fragment in due time.

The third chapter will provide details on the synthesis of kujounins A1 and A2 in our laboratory. Kujounin A2 was synthesized in 7 steps from L-ascorbic acid based on a biomimetic approach. A new biosynthetic pathway is presented that seems likely to produce the kujounins. A key Tsuji-Trost reaction followed by an ozonolysis afforded the core of the natural product in just two steps. The sensitive disulfide moiety was more difficult to install but was accomplished in a few steps. Biological activity studies are pending.

The last chapter discusses the total synthesis of the proposed structure of (–)-himeradine A. An overview of background and previous work accomplished on himeradine A in our lab is provided. The total synthesis was completed in just 17 longest linear steps and only 10 of those steps required column chromatography. This synthesis features a key tartaric acid salt resolution of a piperidine, a B-alkyl Suzuki of two complex fragments, a photoredox conjugate addition, and a transannular Mannich reaction that forms 5 bonds in 1 step. The spectral data was consistent with Shair’s synthetic sample and had some discrepancies with the isolated natural product. Epimers of himeradine A will be synthesized in our laboratory in due time.