The Alkaloids of Papaveraceous Plants: Liv. The Structure of Eschscholtzine

Abstract

Eschscholtzine, a new alkaloid from Eschscholtzia californica, has been shown to be the bismethylenedioxy analogue of 1V-methylpavine (argemonine). The mass spectrometric fragmentation of allcaloids of the pavine type is discussed.Two of us have reported the isolation of a new alkaloid, eschscholtzine, from Eschscholtzia californica Cham.(1) and a mass spectrum* of it showed the molecular formula to be C~~H I~O~N .In the meantime, a fuller mass spectrometric study of eschscholtzine a t Liverpool allowed the correct structure t o be derived which had independently been determined by nuclear magnetic resonance (n.m.r.) and chemical degradation a t Guelph. The mass spectrum of eschscholtzine shows a very small parent peak a t m/e 323 when the hot inlet system was used; however, by direct inlet of the sample, the parent peak increased to about one-third the size of the base peak. In both spectra (hot inlet or direct inlet) only one intense fragment peak appeared a t m/e 188. This behavior is similar to that of the 1-benzylisoquinoline alkaloids (2) but on this basis the only reasonable structure for the fragment ion is (I) which corresponds to m/e 190 and is thus unacceptable.However, the spectra of pavine (IV, R = H) and N-methylpavine (IV, R = Me) parallel that of eschscholtzine in showing a single intense fragment ion a t m/e 190 and one a t m/e 204. These ions are formulated as I1 (R = H) and I1 (R = Me) and their formation can be rationalized as shown below. The nature of the ion from eschscholtzine can now be understood as the aromatic ion (111) and its forination strongly indicated the methylenedioxy analogue (V) of N-methylpavine (IV, R = Me) (argemonine) as the structure of eschscholtzine.The striking similarity of the n.m.r. spectra of argemonine (IV, R = hlIe) (3, 4) and eschscholtzine (V) supported this indication. Both n.m.r. spectra exhibit impressive symmetry and they are largely superiinposable except for the slight shifts described in Table I. The aromatic and N-methyl protons call for no special comiment but the protons of the two methylenedioxy groups appear as a quartet of lines of almost equal intensity: 4.17, 4.21, 4.22, and 4.26 T . The two methylenedioxy groups are thus allnost equivalent but the two protons of the 0-CH2-0 system are not identical as a result of their being in different environments with respect to the aromatic rings. The eschscholtzine molecule is non-planar and may resemble a partly opened hinge. A similar non-equivalence of the methylenedioxy protons has been encountered in the aporphine alkaloids, diceiltrine and bulbocapnine methyl ether (5).

A Caryachnine N-Methosalt From Cryptocarya chinensis and PMR Spectral Characteristics of Some Quaternary Pavine Alkaloids

“…In a study by Barker and Battersby (12), the absolute configuaration of ( -)-caryachine (3) was established as 5S,11S by correlation with ( -)-argemonine (8) of proven configuration. The reported cd curves of the above two compounds (9) are similar to the curve of ( -)-caryachine methoperchlorate (5), which should, accordingly, possess the same 5S, 1 IS configuration.…”

“…Isolation of (-)-caryachtnf. methoperchlorate (5).-The residue (1.86 g) from column fraction 68-98 eluted with 20% methanol in chloroform was dissolved in a minimum amount of hot distilled water.…”

“…sample of (-)-caryachine perchlorate (5) was dissolved in a minimum amount of hot distilled water and treated with an excess amount of saturated potassium iodide solution. The reresulting solution was extracted with chloroform (5x50 ml).…”

“…The quaternary alkaloid fraction was separated from the tertiary alkaloid fraction by solvent partition and precipitation as the reineckate salt, which was then exchanged by an anionic resin into the chloride form. Fractionation of this chloride salt on a silica gel column provided a major alkaloid, which was crystallized as the perchlorate salt (5), mp 211-212°, [a]25D -224°( MeOH). The uv spectrum of this salt showed a single maximum at 291.5 nm, which shifted to 295 nm upon treatment with base, suggesting the presence of a phenolic function.…”

Neocaryachine, a New Pavine Alkaloid from Cryptocarya chinensis, and NMR Spectral Properties of Related Alkaloids

“…Besides the structural elucidation of neocaryachine, we also examined the spectral properties of caryachine N-metho perchlorate [5], a quaternary base previously isolated from C. chinensis (4). Its :H chemical shifts (Table 1) were assigned by nOe studies and double resonance experiments.…”