Study On Total Synthesis Of Neoamphimedine

Neoamphimedine,an important pyridoacridine alkaloid extracted from sponge Xestospongia sp.,is a potent antitumor agent in both in vitro and in vivo tests.Recently,neoamphimedine was characterized as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase Ⅱα,Due to lack of adequate sample of neoamphimedine for further biological testing,the development of neoamphimedine as a therapeutic agent was retarded.Study on the total synthesis of neoamphimedine is thus of great importance and extreme urgency.This work presents our study of the total synthesis of neoamphimedine through two synthetic strategies.One utilized cascade reaction initiated by Au(I)-catalyzed 6-exo-dig cycloisomerization of N-propargylaminoquinones.The other used a cross C-N coupling of indole with phenyl bromide to construct the A/C ring efficiently,and then complete the synthesis of neoamphimedine by Minisci reaction or Bernthsen reaction.Currently,both methods cannot work well and further investigation will be needed.