Synthesis Study Of 3-Substituted Indole Derivatives With Anti-Candida Albican Activities

As the core skeleton of many natural products and active drugs,the synthesis of indole and its derivatives have attracted considerable attention.The synthetic methods with mild reaction conditions,green and pollution-free and atomic economy have won the favor of many chemists,with the improvement of people’s awareness of sustainable development.The development of these methods were mainly to provide methodological reserve for the synthesis of potentially bioactive molecules,such as the synthesis of indole and its derivatives.In this paper,the synthesis methods of indole compound C-3 formylation and thiocyanation were explored.The method was applied to the synthesis and structural modification of 3-substituted indole derivatives with anti-Candida albicans activity,and all synthetic compounds were also investigated for their activities against Candida albicans.The details are as follows:We have developed a visible light promoted indole C-3 formylation reaction.The reaction used cheap and easily available organic dye eosin Y（EY）as the photocatalyst,and the whole process was carried out in air.The reaction exhibited good functional group tolerance under environmental conditions,and giving the target products in good yields.The mild green reaction conditions without transition metal-free are the characteristics of this scheme.In addition,we have developed a green,simple and efficient indole C-3thiocyanation reaction.In this scheme,both N-substituted indoles and free NH-indoles have good functional group tolerance,and the yields were in the range of 58.0-98.7%.The scheme has the characteristics of mild reaction conditions,simple post-treatment and short reaction time.Based on the preliminary experimental studies of our research group,we have synthesized a series of indole compounds.The structure of compounds were confirmed by the spectrums of ¹H NMR and ¹³C NMR.All synthesized compounds were tested for anti-Candida albicans activity in vitro by the microdilution method.The3-phenylindole series of compounds have good activities against FLC-resistance Candida albicans,with MIC₅₀values in the range of 8.75-46.57μg/m L.The3-thiocyanatoindoles showed good antibacterial activities against FLC-resistance Candida albicans when used alone（4a-4c,4j-4k）,and the compound 4c MIC₅₀is 10.11μg/m L.