Enantioselective Synthetic Studies Of Antitumor Natural Product Pseudolaric Acid B

This thesis is mainly focused on enantioselective synthetic studies of antitumor natural product Pseudolaric acid B.Pseudolaric acid B(PLB),a novel deterpenoid isolated from Cortex pseudolaricis by Chinese scientists in 1980's consisting of a rarely seen transfused[5-7]-bicyclic core substituted with an acetoxy group and a lactone at the ring junction,exhibited significant cytotoxic activities against numerous tumor cell lines and strong antifungal activity.A concise illustration of the isolation,structure identification,and biological activity of pseudolaric acid B is described,and relevant synthetic research of pseudolaric acid B has been systematically summarized.A key tricyclic precursor for the total synthesis of pseudolaric acid B has been enantioselectively synthesized in 10 steps for the longest linear sequence from the commercially available material 1,3-Dichloro-2-methylenepropane,which featured the Sharpless asymmetric epoxidation,cyanide ring-opening reaction of epoxide with Ti(O-iPr)4/TBAF/TMSCN and intramolecular[5+2]cycloaddition reaction as the key transformations.The attempt of SmI2-mediated reductive opening of the oxygen bridge is under the way.