| One of the more demanding synthetic requirements in the construction of polyketide-derived secondary metabolites is the stereocontrolled installation of a 1,3-diol unit. To facilitate this need, a highly selective reduction of acyclic beta-alkoxy ketones to the corresponding syn-1,3-ethylidene acetals was developed. This reduction proceeds in good to high yield (69--94%) with excellent selectivity favoring the all syn-protected 1,3-diol (>200 : 1, syn : anti).; This dissertation also details the complete total synthesis of the antifungal and anticancer agent RK-397. This synthesis utilized an asymmetric catalysis method with relay of stereochemistry and a two-directional chain strategy to efficiently assemble the full polyol domain, as well as, a novel olefin cross-metathesis to append the pentaene unit to the polyol chain.; Due to the unclear stereochemical assignment and biological activity of arenolide, a total synthesis of this natural product was recently initiated. A flexible and concise synthetic route has been devised to allow for rapid production of the necessary stereoisomers. The synthesis hinges on an intramolecular vinylogous macroaldol reaction, recently disclosed by the Sammakia lab, to produce the requisite 14-membered lactone. |
