Secobenzophenanthridine alkaloids

In the course of detailed studies on the chemical constituents of rutaceous plants, genus Xanthoxylum, known to contain the antitumor benzophen-anthridine alkaloids, Ishii et al. (167-173) have isolated four seco amide alkaloids arnottianamide (206), iwamide (207), integriamide (208), and isoarnottianamide (209). Sharma et al. (174) have also found arnottianamide (206) in Toddia Asiatica. 

It was postulated (169) that these amides are 8,8a-secobenzophenanthridine alkaloids produced by oxidative cleavage of ring B of the corresponding benzophenanthridines. The success of Baeyer-Villiger-type oxidations of the immonium bond of benzophenanthridine skeletons (168,171,172,175) indicates that this type of oxidation could be a real biological pathway. 

Data concerning plants of occurrence, melting points, and spectral features of these alkaloids have been collected by Krane et al. (6). Some characteristic spectral features deserve attention. In IR spectra the amide band appears in the region between 1670 and 1646 cm-1. Among the H-NMR spectra, singlets of the N-methyl amide protons are situated between 82.91 and 3.27, and the 

Four naturally occurring secocularine alkaloids are known secocularine (228), secocularidine (229), norsecocularine (230), and noyamine (231). The first three belong to the 1,2-seco class possessing the characteristic N,N-dimethyl-aminoethyl side chain and oxepine system, and the fourth is a l,a-seco alkaloid 

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Synthesis of all four 8,8a-secobenzophenanthridine alkaloids was carried out chiefly by Baeyer-Villiger oxidation of appropriate benzophen-anthridines (Scheme 32). Thus, arnottianamide (206) was obtained from chelerythrine (210) (172,175), iwamide (207) from N-methyldecarine (211) (168,172), integriamide (208) from avicine (212) (171,172), and isoarnottiamide (209) from nitidine (213) (172,175). The proposed mechanism of this reaction (168,172,175) consists of initial attack of the peroxide ion on the C=N+ double bond followed by rearrangement and hydrolysis. 

The methyl ester of corydalic acid (413) can be isolated from Covydalis incisa when the plant is in the vegetative stage and can be classed as a secobenzophenanthridine alkaloid (G. Nonaka, T. Kodera and I. Nishioka, Chem.Pharm.Bull., 1973, 21, 1020). It has been synthesised by the condensation of the acid anhydride (410) with the imine (411) to give an acid that is decarboxylated to a mixture of geometrical isomers, of which (412) is hydrolysed, esterified and reduced to ( )-meth-y1 corydalate (413) (Cushman and W.C. Wong, J.org.Chem., 1984, 49, 1278). It has also been prepared by the reduction, oxidation and esterification of the olefin (414), prepared from the berberine alkaloid corysamine (Hanaoka, S. Yoshida and C. Mukai, Chem.Comm., 1984, 1703). 

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