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

Abstract 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.