Speaker: Dr. Paul R. Blakemore, Department of Chemistry, Oregon State University

Title of Talk: Synthetic Studies Directed at the Polyketide Natural Products Mensacarcin and Chalaniline A

Abstract: Work focused on the total synthesis of two starkly different bioactive polyketide natural product molecules will be presented. The first target, mensacarcin, is a highly oxygenated anthracenyl-type epoxyquinol from soil-dwelling Streptomyces bacteria that broadly inhibits metabolism and cell motility while exhibiting selective cytotoxicity to melanoma cell lines. Our ongoing efforts to develop a stereo- and regio-controlled synthetic entry to mensacarcin that avoids circuitous operations will be described. Key stages of the approach include: a benzyne-furan cycloaddition to forge an oxabridged anthracenyl template, a singlet oxygen mediated photooxidation to install a regio-differentiated direct precursor to the epoxyquinol core, and an asymmetric ring opening (ARO) reaction to achieve an enantioselective regiodivergent resolution of a racemic strained oxabicycle intermediate. Problems encountered in setting the correct stereochemical configurations at C1 and C10 of the target will be discussed alongside the evaluation of a range of potential tactics to solve the conundrum presented by mensacarcin.

The second target of interest, chalaniline A, is a cytotoxic condensed aromatic compound from an ascomycete fungus that contains an unusual aminofulvene fused chromone moiety. Two complementary approaches to this curious system will be described; one, a conventional route based on a step-efficient double annulation process and the other, a wholly different strategy in which a ferrocene template is used as a cyclopentadiene ring surrogate.