Octahydro-1,6-naphthyridin-4-ones

Based on the bicyclic structure of the octahydro-1,6-naphthyridin-4-one 92, a chemical library was prepared by employing a solid-phase synthesis technique and evaluated by an EC activation assay that measured the production of macrophage inflammatory protein 1 beta (MIPljS), a marker of EC activation by IFNy. Reaction conditions were first established by using SynPhase lanterns as solid supports. Allenoate 93 was subjected to a phosphine-catalyzed [4 + 2] annulation reaction with A-tosylbenzaldimine 94. 

Cruz, D., Wang, Z., Kibbie, J., Modlin, R., and Kwon, O. (2011). Diversity through phosphine catalysis identifies octahydro-l,6-naphthyridin-4-ones as activators of endothelium-driven immunity. Proc Natl Acad Sci USA 108 6769-6774. 

The resulting tetrahydropyridine 95 was then converted into dienol ether 96 using a Tebbe reagent. A subsequent e Jo-selective Diels-Alder reaction with A-tosylbenzaldi-mine 94 produced octahydro-l,6-naphthyridin-4-ones 97a,b with a diastereomeric ratio of 97 3 (Scheme 16.14). ... 

SCHEME 16.14. Solid-phase synthesis of octahydro-l,6-naphthyridin-4-ones. Academy of Sciences. AU rights reserved. 

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