Synthetic Studies On MPC1001

MPC1001 is a natural product isolated from the fungus Cladorrhinum sp. KY4922. MPC1001 exhibited antimicrobial activity and antiproliferative activity against human tumor cell lines, especially against HCT 116. Due tothe great medicinal potentialof MPC1001, scientists have made many efforts towards its total synthesis and obtained some great progresses. Fragments of MPC1001 have been successfully synthesized, and several total syntheses of the same family members, Aranotin, Acetylaranotin and MPC1001 B and some derivatives have been reported. However, the total synthesis of MPC1001 has not been reported.Here we disclose our research process on the total synthesis of MPC1001. Several synthetic stretgies have been attenpted and some key intermediates were obtained. Strategy Iutilizes Cope rearrangement to furnish the core oxepine ring and constructs the pyrrole ring and side-chain structure in later stage. This synthetic route takes(L)-pyroglutamic acid as a starting material, through methyl esterification, protection of amino group, reducing the carbonyl group of the pyrrole ring structure and bromination to construct thesubstrate for Sonogashira coupling reaction. Then alkynyl reduction, oxidation, epoxidation and Wittig reaction were used to synthesize the precursor of Cope rearrangement reaction, followedby the 15-membered lactone ring construction. An epoxidation precursor was successfully obtained, but the subsequent epoxidation encountered difficulties. Strategy II utilized a straight-chain precursorto finish the Cope rearrangement. This route overcame the epoxidation problems in route I, but further diene construction is still pending. Strategy III proposed asimpler linear diene for Cope rearrangement which furnished the core oxepine ring.The key steps will be the pyrrole ring construction and the connection with the diketopiperazine part.These studies provided theoretical and experimental basis for synthetic research on MPC1001 and route III has the promise to finish the first total synthesis of MPC1001.