Synthesis Of Betulin Derivatives Containing Oxadiazole (Thiadiazole)

As an important source of anticancer drugs,natural compounds have become a hot spot in the research of natural organic drugs in recent years.Pentacyclic triterpenoids have been regarded as key research compounds because of their low toxicity,strong targeting effect and small adverse reactions.Betulin is a pentacyclic triterpenoid compound,which is widely found in natural plants such as jujube seed,asparagus,birch bark and leaves,persimmon stems,etc.Pharmacological studies show that betulin itself is non-toxic and has a variety of biological activities,such as anti-tumor,anti-inflammatory,etc.Therefore,as an important drug intermediate,betulin is used in food,cosmetics,medicine and other industries.In recent years,in order to improve the anti-tumor and pharmacokinetic properties of betulin,many studies have been carried out on the structural characteristics of betulin.The research shows that the introduction of active groups at the c-30 position of betulin can improve its anti-cancer and anti HIV activities,and increase its water solubility.In this paper,two series of betulin derivatives were designed and synthesized from betulin extracted from birch bark by using the principle of active group splicing.In the first series,thiosemicarbazide group was introduced into betulin at position 30and used as a ligand to coordinate with various transition metals to synthesize metal complexes.Then,the structures of the complexes were characterized by ~1H-NMR,FT-IR and MALDI-TOF-MS.In series 2,10 betulin derivatives containing 1,3,4-thiadiazole and 1,3,4-oxadiazole were synthesized by bromination,nucleophilic substitution and hydrazinolysis at position 30 of betulin,and their structures were characterized.In the future,the synthetic betulin derivatives will be tested in cells to provide a theoretical basis for the in vitro activity of betulin derivatives.