The [4+2] cyclizations between vinyl isocyanates and enamines have been developed by our group to synthesize a wide range of pyridone systems. ( S )-camptothecin, a potent anticancer compound was considered as an ideal natural product to target using the cyclization chemistry between enamines and vinyl-isocyanates. Major challenge in this project was the construction of functionalized enamine component. Two distinct methods were used to construct the lactone. We investigated the possibility of ethylating the lactone using a wide array of bases.
A carbazole based enamine was identified and synthesized as a viable enamine partner for the key [4+2] cyclization. The feasibility to undergo a [4+2] cyclization between the carbazole based enamine and the vinyl isocyante was investigated.
A novel route to approach the functionalized lactone was also developed. This route brought us almost to the end of the total synthesis of ( S )-camptothecin.
