Synthesis Of Novel Pleuromutilin Derivatives

With unique antibacterial mechanism,pleuromutilin is the hot spot of antibiotic research.Retapamulin,the first pleuromutilin approved for human use in 2007,had made such antibiotics from veterinary to human use change.And a number of human use antibiotics are in clinical stage.Except antibacterial activity some pleuromutilin derivatives have shown their potential in antineoplastic and anti-inflammation through recent studies.Our laboratory had synthesized a series of pleuromutilin derivatives containing the amino groups and found that two compounds inhibited more than one human colorectal cancer cells.This thesis includes two parts.Firstly two compounds with cinnamic acid structure and two compounds with acetophenone structure were designed and synthesized by transforming pleuromutilin derivative's C14 side chain.And the pleuromutilin derivatives with cinnamic acid structure are found that have immunosuppression activity.Secondly the reaction condition of Beckmann rearrangement was optimized.The low water solubility of pleuromutilin drugs reduces the activity in vivo.In order to increase the water solubility and human bioavailability of these compounds we transformed five-membered ring of pleuromutilin into six-membered amide.Traditional strong acid catalysts corrode equipments and polluted the environment.So we chose environmental ionic liquid to catalyze the Beckmann rearrangement of pleuromutilin and the catalysts could be recycled.