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Toward the total synthesis of FR901483: concise synthesis of the azatricyclic skeleton.

ABSTRACT: 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.

SUBMITTER: Simila ST

PROVIDER: S-EPMC2536713 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Toward the total synthesis of FR901483: concise synthesis of the azatricyclic skeleton.

Simila Suvi T M ST Martin Stephen F SF

The Journal of organic chemistry 20070608 14

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 ...[more]

PMID: 17555359

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