A method to synthesize anticancer drug N-（ 4- hydroxyphenyl） retinamide （4-HPR）on a large scale is described. It consists of the preferred steps of reacting all-trans retinoic acid with thionyl chloride to form re...A method to synthesize anticancer drug N-（ 4- hydroxyphenyl） retinamide （4-HPR）on a large scale is described. It consists of the preferred steps of reacting all-trans retinoic acid with thionyl chloride to form retinoyl chloride and then reacting with triethylamine to generate retinoyl ammonium salt which in turn is reacted with p-aminophenol to eventually produce 4-HPR. This process can overcome many scale-up challenges that exist in the methods reported in the literature and provide an easy, mild and high yield route for large scale synthesis of 4-HPR. Moreover, the effects of the molar ratios of the reagents on the yield are examined. The best molar ratios are a 2.0 molar equivalence of thionyl chloride and a 3.0 molar equivalence of paminophenol to retinoic acid, and the total yield is 80. 7%.展开更多
基金This work was financially supported by the Natural Science Foundation of China(21925110,21890751,91745113)the National Program for Support of Top-Notch Young Professionals+9 种基金USTC Research Funds of the Double First-Class Initiative(YD2060002004)the Key R&D Program of Shandong Province(2021CXGC010302)the Major Program of Development Foundation of Hefei Center for Physical Science and Technology(2016FXZY001)the Users with Excellence Project of Hefei Science Center CAS(2021HSCUE004)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB36000000)the Anhui Provincial Natural Science Foundation(1808085MB26)The authors also appreciate the support from the beamline 1W1B of Beijing Synchrotron Radiation Facility(BSRF,Beijing,China)the beam-lines BL11U,BL10B,and BL12B-a of National Synchrotron Radiation Laboratory(NSRL,Hefei,China)the fellowship of China National Postdoctoral Program for Innovative Talents(BX2021280)the fellowship of China Postdoctoral Science Foundation(2022M710141).
文摘A method to synthesize anticancer drug N-（ 4- hydroxyphenyl） retinamide （4-HPR）on a large scale is described. It consists of the preferred steps of reacting all-trans retinoic acid with thionyl chloride to form retinoyl chloride and then reacting with triethylamine to generate retinoyl ammonium salt which in turn is reacted with p-aminophenol to eventually produce 4-HPR. This process can overcome many scale-up challenges that exist in the methods reported in the literature and provide an easy, mild and high yield route for large scale synthesis of 4-HPR. Moreover, the effects of the molar ratios of the reagents on the yield are examined. The best molar ratios are a 2.0 molar equivalence of thionyl chloride and a 3.0 molar equivalence of paminophenol to retinoic acid, and the total yield is 80. 7%.
