Asymmetric Total Synthesis Of Natural Products Capitulactones A-C And Murrayazoline Alkaloids

This thesis aims at the asymmetric synthesis of the natural products Capitulactones A-C and three Murrayazoline alkaloids.The specific work can be divided into the following two parts: Chapter 1.Asymmetric Total Synthesis of Natural Product Capitulactones A-CCapitulactones A-C are three novel natural products isolated from the Curculigo capitulate by academician Yue Jianmin of Shanghai Institute of Materia Medica.The configuration is confirmed by methods such as nuclear magnetic,high-resolution mass spectrometry,CD spectrum,Structural characterization showed that Capitulactones A-C contained a common conjugated diene heptalactone and dihydrofuran skeleton.Asymmetric synthesis of Capitulactones A-C was carried out on the potential bioactivity of Capitulactones A-C and the construction of a conjugated diene heptalactone and dihydrofuran skeleton with synthetic challenges.The construction method of conjugated diene heptalactone dihydrofuran skeleton was explored.The method of constructing the heptalactone dihydrofuran structure and then introducing the conjugated diene was attempted.And The strategy of constructing conjugated diene heptalactone ring with dihydrofuran ring as the basic framework has been explored.Based on the above research work,we speculated on the biosynthetic pathways of three natural products.Inspired by the biosynthesis pathway,the structure of conjugated diene heptalactone and dihydrofuran was successfully synthesized from benzodihydrofuran skeleton by oxidation-reduction reaction,and the first asymmetric total synthesis of Capitulactones A-C and their isomers was completed.This synthesis provided ample samples for bioactivity testing,and active assays are currently in progress.Chapter 2.Asymmetric Total Synthesis of Murrayazoline Carbazole AlkaloidsCarbazole alkaloids have been the focus of biochemists for their diverse biological activities and unique structures.Murrayazolinine,Cyclomahanimbine and Murrayazoline have been isolated multiple times from Murraya,and the absolute configuration of the optically active Murrayazoline remains unknown.The absolute configuration of Murrayazoline with optical activity has not been elucidated.There is currently no report on asymmetric synthesis of such compounds.Therefore,it is of great significance to carry out asymmetric synthesis of these natural products.Dr.Shao Jidong of our research group constructed the chiral and tricyclic lactone precursor structure by enantioselective catalytic decarboxylation Diels-Alder reaction developed by Wang Group,and constructed a chiral bridged tricyclic benzopyran skeleton through reduction-acidification,and the asymmetric total synthesis of Murrayazolinine was finally completed in 13 steps of 3% total yield.In order to simplify Dr.Shao's synthetic route,the asymmetric total synthesis of Murrayazolinine,Cyclomahanimbine and Murrayazoline can be efficiently completed.After obtaining the precursor structure of chiral tricyclic lactone,we constructed a chiral bridged tricyclic benzopyran skeleton containing ester group outside the ring by intramolecular hydrolysis-intercalation Michael reaction,which greatly simplified the conversion process of tertiary alcohols for Murrayazolinine.Then,the key carbazole was synthesized by aromatization reaction with cyclohexenone as benzene donor and ?kermark-Kn?lker oxidative coupling reaction.Finally,the asymmetric total synthesis of three natural products was accomplished efficiently and concisely in 9-10 steps with overall yields of 16%,12% and 6%,respectively.At the same time,the absolute configuration of(+)Murrayazoline,which was separated by Furukawa group,was determined.