Chemistry of 8,13-dioxoberbines

The aporhoeadane alkaloids

“…6,61 Berberine (6, Scheme 79) was dimerized to oxybisberberine (256) using postassium ferricyanide. The dimer could be cleaved nearly quantitatively with pyridine hydrochloride in pyridine to yield the homoannular α-ketocarbinolamide 7 (which could also be called prechilenine or 8,13-dioxo-14-hydroxycanadine) along with recovered berberine in a 1:1 ratio.…”

“…62 While the methods outlined above utilized a natural product derivative as the starting material, some other approaches have built the framework from simpler substrates. In one example, Kessar et al described a chilenine synthesis that used the known base induced carbinol-carbonyl transposition, 6,61 but constructed the substrate, prechilenine, from simple building blocks (Scheme 80). 63 Their synthesis began with the known condensation 64 of dihydroisoquinoline 217 and 6,7-dimethoxyphthalide (258), which was prepared from ovanillin.…”

“…61 Treatment of the homoannular α-ketocarbinolamide (7) with aqueous sodium hydroxide readily yields noroxyhydrastine (314) as the major product, along with Perkin's anhydroberberilic acid (315, Scheme 103). 6 Scheme 103. Oxidative cleavage of the homoannular α-ketocarbinolamide prechilenine.…”

“…As an aside, this is significant because treatment of the homoannular α-ketocarbinolamide with ammonium hydroxide incites the reverse reaction. 6,61 The hydroxyl group is lost to give the violet iminium salt 319, and the lactam is subsequently cleaved. Sodium borohydride was then used to reduce the α-ketoiminium ion (320) to the corresponding amino alcohol, which spontaneously lactonized.…”

“…61 Alternatively, treatment with 10% methanolic hydrogen chloride accomplishes the same result (Scheme 107). 6 The drastic color change that occurs during the reaction suggests the intermediacy of iminium ion 17, which is blue-black in color.…”