1335104-93-2Relevant academic research and scientific papers
Total synthesis of 7-ethyl-10-hydroxycamptothecin (SN38) and its application to the development of C18-functionalized camptothecin derivatives
Yao, Yuan-Shan,Liu, Jia-Li,Xi, Jie,Miu, Bukeyan,Liu, Guai-Sai,Wang, Shaozhong,Meng, Linghua,Yao, Zhu-Jun
supporting information; experimental part, p. 10462 - 10469 (2011/10/09)
A new chemical synthesis of SN38, the active metabolite of the camptothecin prodrug irinotecan, has been achieved in 12 steps from simple, commercially available starting materials. A mild and efficient FeCl3-catalyzed Friedlaender condensation was successfully applied to construct the AB ring system. Functionalization of the C ring was accomplished by a vinylogous Mukaiyama reaction of an in situ generated N-acyliminium intermediate with a silyl enol ether. An intramolecular oxa Diels-Alder reaction efficiently constructed the D and E rings in one step. Successive asymmetric dihydroxylation and I2-based hemiacetal oxidation furnished the stereochemistry of SN38 with high enantiopurity. Utilizing the ABC-ring intermediate and a functionalized silyl enol ether permitted the synthesis of a number of new C18-functionalized SN38 derivatives. Several of the novel SN38 derivatives that bore a C10 methoxy group were found to exhibit comparable or more potent inhibitory activity against the proliferation of cancer cells relative to SN38.
