The Synthesis Of Cichoric Acid And Rivavoxaban

This dissertation work includes two chapters.Chapter one is about the synthesis of Cichoric acid.Cichoric acid is a natural product with biological activity,which was extracted from Echinacea purpurea.It has the ability to regulate humans immune system,and is mainly used for anti-inflammatory,anti fungal,anti bacteria,anti parasite,antitumor and antiviral drugs.Particularly,cichoric acid is able to inhibit hyaluronidase and HIV-1 integrase.It is expected to be a anti HIV-1 drugs.At present moment,cichoric acid was usually extracted from the plants.This procedure is too costly.In order to solve these problems,We developed a synthetic process of chicory acid.The crude product of cichoric acid was prepared from tartaric acid and and hydroxyl-protect caffeic acid via acylation in non-polar solvents and deprotection.High purity cichoric acid was obtained by forming stable calcium ion complexes,hydrolysis and recrystallization.The process have the advantages of low cost,easy operation and environment-friendly.The synthetic process of rivaroxaban was studied in second chapter.Rivaroxaban,which is a small-molecule oxazolidinone derivative,as a potent,selective inhibitor of Xa factor,is used in the prevention of venous thrombo embolism for adult patients after total hip replacement(THR)and total knee replacement(TKR)surgery.In this chapter the reported synthetic routes were reviewed.At first,4-(4-Aminophenyl)morpholin-3-one was reacted with alkyl chloroformate to form alkyl(4-(3-oxomorpholin)phenyl)carbamate,then condensed with(s)-1-chloro-3-[(4-chlorobenzylidine)-amino]-propan-2-ol,which was readily available from(S)-epichlorohydrin and 4-chlorobenzaldehyde in the presence of aqueous ammonia.After the construction of the parent oxazolidinone ring of rivaroxaban,the obtained oxazolidinone Schiff base intermediate was hydrolyzed then acetylated with 5-chlorothiophene-2-carbonyl chloride to give rivaroxaban with high purity.It was noted that 4-chlorobenzaldehyde used as amino protecting group was recyclable.The present process with the readily available raw materials was mild and very convenient to operate.Finally,the impure ingredient of rivaroxaban synthesis process was investigated,the impurities produed during this process were synthesized.