Study On The Composition Of Roasted Tripterygium Wilfordii And Synthesis Of Benzylfluorenone Based On Pd-catalysed C-H Oxidative Coupling

As an important herb for the treatment of rheumatoid arthritis,Tripterygium wilfordii exhibits various pharmacological activities,including immunosuppression,anti-inflammatory,anticancer,insecticidal,neuroprotective,analgesic and anti-HIV effects.In our previous studies,we found that Tripterygium wilfordii roasted with200℃oven showed significant detoxification and enhanced efficacy,as the toxic component Triptolide was transformed into the anti-inflammatory compound1-hydroxy-2,5,8-trimethyl-9-fluorenone.However,1-hydroxy-2,5,8-trimethyl-9-fluore-none is present in Tripterygium wilfordii at very low levels.To address the issue of sourcing this active ingredient,we developed a novel one-pot pd-catalyzed C-H oxidation coupling method for the synthesis of this anthrone-type compound.During our investigation of the pd-catalyzed C-H oxidation coupling synthesis of fluorenone,we also discovered a new type of non-chelating Pd-catalyzed sp³C-H/sp²C-H intermolecular oxidation coupling method for the synthesis of 5-benzylfluorenone.In order to clarify the basis for detoxification and enhanced efficacy of Tripterygium wilfordii after roasted and to enrich the pd-catalyzed C-H oxidation coupling reaction,this paper carried out two parts of research:1)chemical composition analysis of roasted Tripterygium wilfordii and 2)investigation of non-chelating pd-catalyzed C-H oxidation coupling synthesis of 5-benzylfluorenone.（1）Study on the composition of roasted Tripterygium wilfordiiThe extracts of processed Tripterygium wilfordii was separated and purified by various methods,such as ODS reverse-phase column chromatography,silica gel column chromatography,preparative HPLC,and Sephadex LH-20.The chemical structures of the isolated compounds were identified by NMR.25 compounds were separated,and 14 of them were identified.（2）Study on non-chelating Pd-Catalyzed C-H Oxidative Coupling to5-benzylfluorenoneWe have reported for the first time a new sp³C-H/sp²C-H intermolecular oxidative coupling synthesis that does not require a chelating agent as an auxiliary.Using Pd（OAc）₂as the catalyst and Na₂S₂O₈as the oxidant,we synthesized four benzyl-fluorenone compounds through pd-catalyzed sp³C-H/sp²C-H oxidative coupling in a one-pot method using three different benzene compounds,namely,toluene,p-xylene,and1,3,5-trimethylbenzene,with1-hydroxy-2,5,8-trimethyl-9-fluorenone.The structures of several compounds were characterized by NMR and MS.Through single-factor experiments,we further optimized the conditions for the synthesis method,including the oxidant,catalyst,reaction time,reaction temperature,substrate ratio,and whether a chelating agent is needed.The optimized conditions were a temperature of 80°C,reaction time of 1 hour,and a substrate molar ratio of 1:4,with a yield of 73%.