For the aim of enhancing cytotoxicity of artemisinin derivatives with the long term aim of developing new cytotoxic anticancer drugs, O- and C-glycosidation chemistry is applied to dihydroartemisinin in order to attach groups to enhance its binding to DNA, either by intercalation or to the minor groove. Treatment of dihydroartemisinin with boron trifluoride etherate in the presence of l- and 2-naphthalenemethanol gives low yields of both the α- and [beta}-epimers of the corresponding naphthalenemethyl dihydroartemisinin derivatives. The Mitsunobu reaction is used to couple 2-naphthol to dihydroartemisinin to provide the corresponding l- and 2-naphthoxy- l0- dihydroartemisinin, also in low yields. The activated aromatic compound, 1,3,5- trimethoxybenzene is coupled to the glycan derived...[ Read more ]

For the aim of enhancing cytotoxicity of artemisinin derivatives with the long term aim of developing new cytotoxic anticancer drugs, O- and C-glycosidation chemistry is applied to dihydroartemisinin in order to attach groups to enhance its binding to DNA, either by intercalation or to the minor groove. Treatment of dihydroartemisinin with boron trifluoride etherate in the presence of l- and 2-naphthalenemethanol gives low yields of both the α- and [beta}-epimers of the corresponding naphthalenemethyl dihydroartemisinin derivatives. The Mitsunobu reaction is used to couple 2-naphthol to dihydroartemisinin to provide the corresponding l- and 2-naphthoxy- l0- dihydroartemisinin, also in low yields. The activated aromatic compound, 1,3,5- trimethoxybenzene is coupled to the glycan derived from dehydration of dihydroartemisinin by means of boron trifluoride etherate at low temperature; this give the α-epimer in acceptable yield. The stereochemistry of all products has been secured through examination of NMR spectra, and through comparison with known compounds of defined stereochemistry.

Dihydroartemisinin was converted via a known method into allyl- l0-deoxydihydroatemisinin, and by a standard sequence, into the corresponding 3'-propanol derivative. This was converted to the tosylate, and then a series of amino derivatives by reaction with amines in DMF. Oxidation of the alcohol to the carboxylic acid followed by coupling with carbonyl di-imidazole into an N-methylated pyrrole amide suitable for binding to the minor groove of DNA proceeded in very low yield.

Evaluation of cytotoxicities of selected compounds against different cell lines was carried in other laboratories.