Total Synthesis of (−)-Sarain A
journal contributionposted on 2007-10-03, 00:00 authored by Michael H. Becker, Peter Chua, Robert Downham, Christopher J. Douglas, Neil K. Garg, Sheldon Hiebert, Stefan Jaroch, Richard T. Matsuoka, Joy A. Middleton, Fay W. Ng, Larry E. Overman
This article describes the details of our synthetic studies toward the complex marine alkaloid sarain A. Various strategies were conceived, setbacks encountered, and solutions developed, ultimately leading to a successful enantioselective total synthesis. Our route to (−)-sarain A features a number of key steps, including an asymmetric Michael addition to install the C4‘−C3‘−C7‘ stereotriad, an enoxysilane-N-sulfonyliminium ion cyclization to set the C3 quaternary carbon stereocenter, and assemble the diazatricycloundecane core, a ring-closing metathesis to construct the 13-membered ring, an intramolecular Stille coupling to fashion the unsaturated 14-membered macrocycle, and a late-stage installation of the tertiary amine−aldehyde proximity interaction.
diazatricycloundecane corefashioncyclizationproximitysetbackVarious strategiesaminemacrocycleenantioselectiveMichael additionC 3 quaternary carbon stereocenterAThistrategyintramolecular Stilleinstallationsynthesismetathesimemberedarticlemarine alkaloid saraininteractionSarainTotal Synthesissolutionstereotriad