Regio- and stereoselective ring openings of 3-Aza-2-oxabicyclo[2.2.1]hept-5-ene systems with copper catalyst-modified grignard reagents: application to the synthesis of an inhibitor of 5-lipoxygenase.
Treatment of acylnitroso hetero Diels-Alder cycloadducts 2 with organomagnesium reagents in the presence of a catalytic amount of copper induces ring opening to afford predominantly monocyclic anti-1,2-hydroxamic acids 12. Alkylmagnesium reagents were found to give superior regio- and stereoselectivities compared with vinyl and arylmagnesium reagents. This cycloadduct ring opening methodology was applied to the synthesis of a unique cyclopentenyl hydroxamic acid-based inhibitor of 5-lipoxygenase.
Surman
Matthew D
MD
Department of Chemistry and Biochemistry, University of Notre Dame, Indiana 46556, USA.
Mulvihill
Mark J
MJ
Miller
Marvin J
MJ
D001094:Arachidonate 5-Lipoxygenase / Q000097:blood; D001372:Aza Compounds / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D000001:Calcimycin / Q000494:pharmacology; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D002855:Chromatography, Thin Layer; D003500:Cyclization; D006536:Heptanes / Q000737:chemistry*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D006536:Heptanes; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D000001:Calcimycin; D001094:Arachidonate 5-Lipoxygenase