Total Synthesis Of(±)-Salprzelactone And Studies On The Synthesis Of Pyrrolidine Via Oxidation/Aza-cope-mannich Cascade Reaction

This thesis includes two chapters: a) total synthesis of(±)-salprzelactone, b) studies on the synthesis of pyrrolidine via oxidation/aza-Cope-Mannich cascade reaction. First chapter: Total synthesis of(±)-salprzelactoneSalprzelactone, which is a seco-norabietane diterpenoid with an unprecedented carbon skeleton and showed appreciable antibacterial activity, was discovered by Wu and co-workers from the roots of Salvia przewalskii in an antibiotic screening program for new drug leads in 2013.We focused on the total synthesis of(±)-salprzelactone through two synthetic routes. An intermolecular Heck reaction, Diels-Alder reaction and radical reaction, were initially evaluated to construct the central benzene ring in the salprzelactone. However, this strategy was proved to be unsuccessful. Afterwards, the key strategy was changed by using a naphthalene amide as a key intermediate, followed by ortho formylation, intermolecular aldol reaction and lactonization, sequentially, the first total synthesis of(±)-salprzelactone was eventually completed by us. Second chapter: Studies on the synthesis of pyrrolidine via oxidation/aza-Cope-Mannich cascade reactionBecause of high levels of predictable stereo-control and compatibility with most functional groups, the aza-Cope/Mannich reaction has been found significant applications in target-directed natural product syntheses. There were three main methods for generation of iminium ions, including condensation of amines and carbonyl precursors, translation of oxazolidines and cyanomethyl groups. We assumed that iminium ions could be generated in situ by oxidation of substrate containing the 1-(benzylamino)-but-3-en-2-ol functional group arrays. Nonetheless, all our attempts on four substrates with different protecting group had failed. Among them, compound 2-105 converted in high selectivity into epoxide 2-112 in the presence of I2. The further identification of its configuration as well as their subsequent utilization will be studied in the future.