A short synthesis of (+)-narciclasine via a strategy derived from stereocontrolled epoxide formation and SnCl(4)-catalyzed arene-epoxide coupling.
A facile construction of the typical framework of narcissus alkaloids has been realized by virtue of the development of a practical route involving stereocontrolled epoxide formation and SnCl(4)-catalyzed arene-epoxide coupling. To achieve this goal, it proved to be necessary to devise a strategy that would enable chemical transformations to install an epoxy moiety in a congested environment. The successful preparation of a hindered epoxide from O-isopropylidene-protected 4-aminocyclohexenol required three steps consisting principally of controlled bromohydration and base-promoted closure and N-alkylation. It was found that a catalytic amount of SnCl(4) not only maintained the catalytic cycle but also effected clean arylation to form a fused BC ring system. Several tactics that ultimately proved to be unsatisfactory are also discussed in an effort to set important boundary limits on arene-epoxide coupling. The requisite enantiopure 4-aminocyclohexenol was available via an asymmetric cycloaddition of diene to camphor-based chloronitroso. The total synthesis of (+)-narciclasine was realized in nine steps with an overall yield of 19%.
D000470:Alkaloids / Q000138:chemical synthesis*; D000478:Alkylation; D047151:Amaryllidaceae Alkaloids; D020650:Combinatorial Chemistry Techniques; D004852:Epoxy Compounds / Q000737:chemistry*; D015394:Molecular Structure; D031427:Narcissus / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010617:Phenanthridines; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism; D017971:Tin Compounds / Q000737:chemistry*
D000470:Alkaloids; D047151:Amaryllidaceae Alkaloids; D004852:Epoxy Compounds; D010617:Phenanthridines; D017971:Tin Compounds; C023599:stannous chloride; C010753:narciclasine