Synthesis of 5-spirocycle camptothecin using ring-closing metathesis strategy

Camptothecin (CPT) is an important natural product targeting to Topoisomerase I (Topo I). Despite the high antitumor activity, this compound cannot enter clinical trial owing to its high toxicity and low bio-availability. In this project, the ring-closing metathesis (RCM) synthesis strategy was employed to introduce spirocycle functional group in the 5-position of CPT. Thus, in the catalysis of Grubbs II catalyst, 5,5-diallylcamptothecin underwent RCM reaction to give 5-spirocycle CPT compound in 73% yield.