Studies On The Synthesis Of Homoharringtonine Ester Chain And Dihydroisoquinoline Annulation Reaction

This thesis is aiming at the improvement of the chemical synthesis efficiency of the anti-tumor natural medicine Homoharringtonine(HHT). We investigated two key steps of novel total synthesis of homoharringtonine. It consists the following two Chapters:Chapter 1 is on the improvement of synthesis method of HHT ester chain, based on intramolecular C-H bond oxidation of ketone ester reported in 1998 by Yang and co-workers(J. Am. Chem. Soc. 1998, 120, 6611-6612.). We designed and synthesized a series of keto ester derivatives for comparison of the oxidation reactivity(Scheme 1). The results show that ester chain length has significant effect on reactivity. These preliminary studies will facilitate the future improvement on this key the oxidation reaction.In Chapter 2, we studied the electronic effect of the substituents of aromatic system on the annulation reaction of dihydroisoquinoline with the enol silane ether of 5-iodopentyl aldehyde(Scheme 2). We synthesized 3, 4-methylenedioxy-isoquinoline, 3, 4-dimethoxy-isoquinoline to compare reaction efficiency of annulation reaction. The results show that electron-rich aromatic substituents led to the improved chemical yield on the dihydroisoquinoline annulation reaction.