Enantioselective Total Synthesis of the Cephalotaxus Alkaloid (−)-Cephalotine A

Abstract

Cephalotine A, a recently isolated Cephalotaxus alkaloid, was first synthesized enantioselectively through three critical reactions. SmI 2 -mediated radical cyclization of lactone and aldehyde to forge the final ring system, Chang's iridium-catalyzed C−H amidation to construct pyrrolidone stereoselectively, and Carreria's dual Ir/amine catalyzed allylation to install the vicinal tertiary stereocenters.Cephalotaxus alkaloids are structurally diverse polycyclic alkaloids isolated from Cephalotaxus genus plants, which grow very slowly and are endemic to eastern Asia. Since the isolation of (−)-cephalotaxine (CET, 1, Figure 1), the most

Enantioselective Total Syntheses of the Cephalotaxus Alkaloids (−)-Fortuneicyclidins A and B and (−)-Cephalotine B

“…Without rapid hydrolysis, subjecting enol ether 12 to Heck reaction conditions using the sterically hindered dppb ligand [1,2-bis­(diphenylphosphino)­benzene] and Pd­(PPh 3 ) 4 afforded an excellent 85% yield of benzazepine 13 after 3 h at 120 °C, leaving the enol ether unscathed. Notably, compared to our recently reported 11-step approach to 13 , this three-step method considerably enhanced the synthetic efficiency . Hydrolysis of enol ether 13 promoted by p -TSA takes place smoothly in acetone to afford aldehyde 14 in good yield.…”

“…Notably, the challenging C-2 hydroxyl group of (−)-fortuneicyclidins A and B can be installed stereospecifically. Herein, the reported asymmetric preparation of the CET core can be further explored in synthesizing related complex alkaloids.…”

“…The formidable C-2 hydroxyl group of fortuneicyclidins A and B and cephalotine B could be stereospecifically set in this approach. As (−)-CET and (−)-cephalotine A have succumbed to total synthesis in our laboratory recently, we herein report our efforts in the total syntheses of (−)-fortuneicyclidins A and B and (−)-cephalotine B.…”