Benzyne cyclization route to benzo[c]phenanthridine alkaloids. Synthesis of chelerythrine, decarine, and nitidine

Kessar, S. V.; Gupta, Y. P.; Balakrishnan, P.; Sawal, K. K.; Mohammad, Taj; Dutt, M. B.

doi:10.1021/jo00243a020

Cited by 60 publications

(32 citation statements)

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“…This structure assignment met objections [4] as contradicting some properties of the substance actually isolated. In particular, a compound having the structure of IV would possess a zwitter-ion character and, hence, must be intensely colored.…”

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8-O-demethylchelerythrine fromMacleaya cordata

et al. 1999

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The fractions obtained upon chromatographic separation of the sum of quaternary benzo [c]phenanthridine alkaloids from Macleaya cordata contain, besides sanguinarine (I) and chelerythrine (1I), an admixture of a substance (III) having the form of golden-brownish needle crystals (whiskers), having a melting point of 220-226~ (from chloroform) and losing transparency at 167~ The IH NMR spectrum of compound III is typical of the 2,3,7,8-substituted quaternary benzo[c]phenanthridine alkaloids and is virtually identical to the spectrum of an alkaloid isolated from Fagara xanthoxyloides, which was called fagaridine and assigned the structure of 7-O-demethylchelerythrine (IV) [1 ].2 A compound having this formula was later synthesized from the corresponding 6-hydroxychelerythrine and identified with the IH NMR spectrum of its quaternary derivative [3]; unfortunately, neither properties of the base of this compound nor a spectrum characterizing its electron structure were reported. This structure assignment met objections [4] as contradicting some properties of the substance actually isolated. In particular, a compound having the structure of IV would possess a zwitter-ion character and, hence, must be intensely colored.In order to elucidate the position of substituents in alkaloid III, we have studied the two-dimensional IH NMR spectra of compounds II and III measured in the COSY and NOESY modes. The parameters of these spectra are listed in Table 1. The COSY spectrum of alkaloid II exhibits a crosspeak between the high-field signal of the methoxy group and the signal from H 9 proton, which indicates that the methoxy group is localized at C 8. Accordingly, the methoxy group responsible for the weak-field signal occurs at C 7. Not a single proton signal yields a cross-peak with the weak-field signals of methoxy groups. The NOESY spectrum of compound II, as well as the COSY spectrum, exhibits a cross-peak between the signal of the H 9 proton and the high-field signal of the methoxy group and no cross-peaks between the weak-field signals of methoxy groups and the signals from other protons.The COSY and NOESY spectra of compound III contain no cross-peaks between the signals ofmethoxy group and the signals of other protons. This fact indicates that the methoxy group in this compound occurs at C 7, while the hydroxyl group is localized at C s.Thus, the isolated alkaloid III can be identified as 8-O-demethyichelerythrine, which was described in [5] as methyldecarine iodide. The same compound, called isofagaridine, was synthesized (in the chloride form) as reported in [6]. Thus, compounds referred to as fagaridine [1], N-methyldecarine [5], and isofagaridine [6] are essentially the same alkaloid having the formula of compound III. This implies that the corresponding alkaloid isolated in [ 1] was misinterpreted and should be assigned structure IlL A comparative TLC analysis of the extract of quaternary alkaloids from Macleaya microcapra and compound III showed that the latter compound is present in the plant in its native form ...

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8-O-demethylchelerythrine fromMacleaya cordata

et al. 1999

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“…The commercially available material 2,3-dihydroxybenzaldehyde 1 was converted to 3-alkoxy-2-hydroxybenzaldehydes 2ae2g based on the known method [30]. Analogously to the reported procedures [31], reactions of intermediates 2ae2g and diethyl malonate produced ethyl 8-alkoxy-2-oxo-2H-chromene-3-carboxylates 3ae3g.…”

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Design, syntheses, structure–activity relationships and docking studies of coumarin derivatives as novel selective ligands for the CB2 receptor

Han

Zhang

Hua

et al. 2015

European Journal of Medicinal Chemistry

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“…In particular, compounds with substituents directly flanking the endocyclic nitrogen atom have thus far been very inconvenient to produce. [27,28] By raising the reaction temperature when we attempted the synthesis of E-2-[2-(4-dimethylaminophenyl)vinyl]benzonitrile (8; Scheme 3) from 4-dimethylaminobenzaldehyde (5) and 2-methylbenzonitrile (6) as given in ref. [29], we surprisingly obtained 7 a as the main product (Scheme 2).…”

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confidence: 99%