Two cyclizations rapidly convert a linear precursor, resembling an oxidized keramadine, to agelastatin A.  A facile and highly diastereoselective C-ring formation via a 5-exo-trig cyclization or Nazarov 4p-electrocyclization, proceeding through a deep-red colored intermediate, constructs the three contiguous stereocenters of the cyclopentane core found in agelastatin A and nagelamide J.  A possible templating effect was discovered in a solvent-free, silica gel-assisted reaction that enables the final B-ring closure.  Initial studies on an enantioselective route, bioactivities of designed derivatives, and synthesis of biological probes will be disclosed.

Bioinspired total synthesis of Agelastatin A

244th National Meeting (2012)

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