Total Synthesis Of Natural Products Aplykurodinone-1,Fuliginosin A,Diptoindonesin G And Analogues

This thesis discusses the total synthesis of several natural products and analogues with novel methods.Of all of the classes of natural products,steroids have perhaps had the most enduring role in prompting new ideas in total synthesis.A not insignificant body of organic chemistry has been discovered in the context of pursuits directed to the total synthesis of steroids.Apparently,this interest continues to the present day.The aplykurodines are a family of highly degraded marine steroids that show cytotoxic activities towards a variety of human cancer cell lines.Oligostilbenes are a class of highly oxygenated natural products comprising more than two stilbene units.These exhibit a wide variety of pharmacological activities.Dip G showed anti-proliferation effect in murine leukemia P-388 cells and immunosuppressant activity.A concise,stereoselective,and protecting group free strategy was used in the total synthesis of aplykurodinone-1 from commercial available Hajos-Parrish ketone.The synthetic approach features a sequence of aerobic allylic oxidation and elimination step.The key intermediate for this synthesis was formed by a stereoselective intramolecular radical cyclization.Several highly substituted benzofuran-containing natural products were prepared by a sequential Rh-catalyzed benzannulation and Pd-catalyzed cross-coupling reaction.The scope and limitation of the Rh-catalyzed carbonylative benzannulation was investigated in the context of natural product synthesis for the first time.We also developed a versatile synthetic strategy for the synthesis of natural product diptoindonesin G and its analgues as selective modulators of estrogen receptors.The strategy involves a regioselective dehydrative cyclization of arylacetals,a regioselective bromination of benzofurans,a sequential cross-coupling of bromo-benzofurans with aryl boronic acids,and a BBr₃-mediated tandem cyclization and demethylation.Some of the analogues were also synthesized based on the modification of Dip G's structure.After the test of their bioactivity toward the MCF7 cells,the analogue with much higher bioactivity was dicussed.This result paved the way for further structure activity relationship studies and the development of new chemical probes for estrogen acceptors.