Derivatizations On The Meso-Position Of Porphyrins Based On Oxidative Coupling Reactions

As photosensitizers for photodynamic therapy,porphyrins are clinically used to treat cancers such as breast cancer,eye cancer,colorectal cancer,brain and neck cancer.Nowadays,with the development of porphyrin synthesis,they also play an increasingly important role in biomimetic chemistry,solar energy utilization,special materials,and sonodynamic treatment.Although the application scope of porphyrin derivatives is becoming wider and wider,due to its complicated structure and difficult synthesis,the porphyrin compounds have relatively limited derivation methods,and there are few novel skeletal structures to be developed.So,the function and structure expansion of porphyrins have been limited.This thesis focuses on the study of the derivatization methods on the meso-position of porphyrins.The porphyrins and chlorins are directly cross-coupled with aromatic compounds by oxidant coupling reactions to synthesize potentially biologically active porphyrins and chlorins derivatives.1.We found that the chlorin substrates and the aromatic amine compounds ca n indeed undergo the amination reaction on the meso-position of chlorins under the oxidation conditions of PIFA or NaAuCl₄·2H₂O.In addition,we examined the optical properties of the chlorin derivatives.It was found that the derivatized products on the meso-position of porphyrins were indeed red-shifted for the absorption wavelength,and the maximum absorption wavelength can be as high as 645 nm.At the same time,we conducted a preliminary study on the photodynamic activity of these compounds by in vitro CCK-8 experiments,and found that some compounds?4a and 5a?showed better photodynamic therapeutic activity.2.We found that for different phenol or naphthol substrates,under the oxidative conditions of DDQ,the coupling of porphyrin meso carbon with carbon or oxygen atom can be obtained in high?up to 93%?yields.Moreover,the corresponding meso-position carbon-oxygen coupling products were obtained for the porphyrin substrates of different central metals?nickel or palladium?.Interestingly,we obtained a product with different substituents in the meso-position of porphyrin through a multi-component reation.It will enriched the structure diversity of porphyrin derivatives.3.We first used the environmentally friendly electrochemical catalysis method to achieve the oxidative coupling reaction between porphyrins and different substrates,thereby further simplifying meso-derivatization process of porphyrins.The carbon-oxygen coupling reaction?phenol substrates?,the carbon-nitrogen coupling reaction?aniline substrates?and the carbon-carbon coupling reaction?naphthol,indole substrates?were successfully achieved,providing a greener and more convenient pathway to meso-derivations of porphyrin.