A Short Synthesis of (+)-Narciclasine via a Strategy Derived from Stereocontrolled Epoxide Formation and SnCl₄-Catalyzed Arene-Epoxide Coupling

Abstract

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%.

The factors that influence the elution order for the resolution of amino acids on vancomycin phase using the polar‐organic mobile phases after their pre‐column derivatization with electrophilic reagents

“…Note that the chlorine atom is larger in size than fluorine and the steric effect resulting in the change in chiral recognition pattern is believed to be more significant. The steric effect has been wisely applied in the asymmetric synthesis to obtain enantiomer with high purity (Elango and Yan, 2002).…”

Cycloadditions with StereoselectiveCNBond Formation in Total Syntheses

“…Yan and coworkers reported on the enantioselective synthesis of the antineoplastic compound (þ)-narciclasine 179 (isolated from various sources of Narcissus bulbs) with the chiral nonracemic chloronitroso camphor derived reagent 175 (Scheme 41.37). 82,83 This reagent was prepared by oxidation of the oxime 174 of ketopinic ester with t-butyl hypochlorite. The asymmetric cycloaddition of 175 to the protected meso cyclohexa-3,5-diene-1,2-diol 176 followed by hydrolysis delivered the desired 3,6-dihydro-1,2-dihydrooxazine 177, cleavage of the NÀO bond was realized directly with Al-Hg to afford 85% of the 4-aminocyclohexenol 178 with an enantiomeric excess superior to 99% because only one enantiomer was detected by chiral HPLC.…”

Synthesis of Amaryllidaceae Constituents - An Update

“…38 Enantiomerically pure amino alcohol 90 was derived from acetonide 88 as described in section 2.3 (Scheme 19). Protection of the amino and hydroxyl functionalities was followed by the epoxide formation via treatment of a mixture of bromohydrines 101 and 102 with base.…”