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Toward the Total Synthesis of FR901483:  Concise Synthesis of the Azatricyclic Skeleton

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journal contribution
posted on 06.07.2007, 00:00 by Suvi T. M. Simila, Stephen F. Martin
A concise synthesis of the azatricyclic core of FR901483 has been accomplished using a novel strategy that involves a nucleophilic addition to an N-acyl iminium ion, a ring-closing metathesis, a diastereoselective hydroboration, and a lactone−lactam rearrangement that worked well in a preliminary model study. Extension of this approach to the synthesis of a more highly functionalized intermediate that could be transformed into (−)-FR901483 first required the development of a new protecting group, the 1-ethylallyloxycarbamate group, for amines that may be removed under mild conditions. However, because the stereoselectivity in a key step in which a functionalized allyl zinc reagent was added to an intermediate hydroxy-substituted imine was low, this route to (−)-FR901483 is no longer being pursued.