Hetero Diels-Alder synthesis of 3-hydroxypyridines: access to the nosiheptide core.
The 1-azadiene hetero Diels-Alder reaction of silylated enol oximes with alkynes was investigated and was optimized to furnish 2,5,6-trisubstituted 3-hydroxypyridines in high yields in one simple operation. Importantly, monosubstituted alkynyl ketones were found to lead to the formation of the 6-isomer with exceptional regioselectivity (>95:5). This methodology was applied to a scaleable synthesis of the core structure of the potent antibiotic nosiheptide. Protecting groups were optimized, which led to a racemization-free seven-step synthesis of the key building block.
Lu
Jin-Yong
JY
MPI für molekulare Physiologie, Otto-Hahn-Strasse 11, D-44227 Dortmund, Germany.
Arndt
Hans-Dieter
HD
D002384:Catalysis; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013844:Thiazoles / Q000737:chemistry
D011725:Pyridines; D013844:Thiazoles; C014047:hydroxypyridines; C014134:nosiheptide