Synthesis Of Dihydroartemisinin-Amino Dithiocarbamate Derivatives

Artemisinin is a very effective antimalarial drugs,and avariety of artemisinin derivatives has been developed,In addition,it also showed anti-tumor,anti-pregnancy and other biological activity.Sulfone compounds wassuperiorto artemisininin the anti-malarial aspects,but there was no studies in the anti-tumor area.At present,a variety of nitrogen-containing heteroatom compounds have been found,in which the nitrogen atoms are predominantly in the form of amines and amide bonds.Commenced withdihydroartemisinin,using the principle of active superposition,variety of aminodithioformate were synthesized.The main contents of this paper are as follows:Part ?:Synthesis of artemisinin-amino-disulfide Derivatives:(1)With dihydroartemisinin as the starting material,dihydroartemisinin-thiomorpholine compoundswas readily accessed through acylationwith oxalyl chloride,and then amination with thiomorpholineAfterwardsdihydroartemisinin-thiomorpholine is oxidized by hydrogen peroxide to obtain the desired compound of the artemisinin derivative3.(2)Monoiodide 8was acquire with 1,6-hexanediol as the starting material,byTBS-protected,and iodine.Then Artemisinin-iodide 9 was achieved by alkylation and iodine.(3)Compound 9 was reacted with carbon disulfide and secondary amine to obtain the target compoundartemison-dithiocarbamate ester.Part ? Synthesis of dihydroartemisinin-piperazine-dithiocarbamate derivatives:Dihydroxy artemisinin-piperazine compound 11 was obtained by the reaction withoxalyl chloride andpiperazine,and then reacted with carbon disulfide and halogenated hydrocarbon to obtain the target compound-dihydroartemisinin-piperazine-aminodithioformate derivatives in"one pot".All the new compounds were confirmed by IR,1H NMR,13C NMR and HRMS Spectrum.