Total synthesis of plakinic acid A. New methodology for the syntheses of cyclic peroxides

Enormous bioactive peroxide-containing natural products were isolated from various sources. We became interested in the plakinic acids, a class of 5-membered cyclic peroxides which possesses anticancer, antibiotic, and antifungal activity. The majority of this thesis describes asymmetric syntheses of plakinic acids by two different approaches: the first employs intermolecular oxetane opening and peroxycarbenium ion addition, and the second involves intramolecular oxetane opening.; Dussault and Trullinger recently developed an asymmetric synthesis of the 3,3,5,5-tetrasubstituted dioxolane acetic acid core of plakinic acids, employing intermolecular oxetane opening by hydrogen peroxide and peroxycarbenium ion addition. We modified this approach to avoid its drawbacks and achieved the first asymmetric syntheses of stereoisomers of plakinic acid A, the first isolated member of this family. Based on NMR comparison we proposed an actual structure of the natural product. Future plan of proving the structure and total synthesis of natural plakinic acid A also was outlined.; Unsatisfied with the limitation of current approach, we next investigated new reactions to synthesis 1,2-dioxolanes: intramolecular oxetane opening by hydroperoxides. This reaction provides a stereospecific route to the 1,2-dioxolanes, offering a new approach to asymmetric syntheses of plakinic acids. The application of similar methodology to synthesis 6-membered cyclic peroxides will also be discussed.; The last two chapters are two side projects I have been working. First is a new methodology to reduce hindered peroxides by Mg/MeOH. Second is the first synthesis of a conjugated arachidonic acid.