The Total Synthesis of 4-Methoxy-6-methylheptadienoic Acid Natural Products

The total synthesis and first structural confirmation of the natural product (±)-cuevaene A I, isolated from Streptomyces sp. HKI 0180, and studies towards the total synthesis of natural products JBIR-23 V and 24 VI, isolated from Streptomyces sp. AK-AB27, are described herein. Chapter 1 gives background to these and related natural products. The previous synthesis of I and the resultant structural ambiguity are also discussed. In Chapter 2, the available methods of forming tetrahydrobenzofuran-1-ols are reviewed before the synthesis of the key aldehyde intermediate II from phenol IV via ketone III is discussed. The triene sidechain was then installed in a stepwise manner through a series of olefination reactions to achieve the total synthesis of I. The structural confirmation of I was then achieved through the comparison of NMR spectroscopic data with the raw isolation data.

The key intermediate for the total synthesis of JBIR-23 V and 24 VI was identified as epoxyquinol VII and Chapter 3 discusses the investigations into its synthesis.

Chapter 4 discusses two complementary methodologies developed to provide access to 4-methoxypentadienoates X, as seen in the sidechain of natural products I, V and VI, from the analogous γ,δ-epoxydienoates VIII through an initial epoxide opening and subsequent elimination of the resulting alcohols IX. The selectivity and substrate scope of the two processes is then investigated.