Toward the total synthesis of FR901483: concise synthesis of the azatricyclic skeleton.
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.
Simila
Suvi T M
ST
Department of Chemistry and Biochemistry, The University of Texas at Austin, 1 University Station A5300, Austin, Texas 78712-0165, USA.
Martin
Stephen F
SF
D000478:Alkylation; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D001372:Aza Compounds; C098358:FR 901483; D006571:Heterocyclic Compounds; D007097:Imines; D009943:Organophosphorus Compounds