Berberis alkaloids XXXV. The structure of nummularine

Abstract

The new N-benzyltetrahydroisoquinoline alkaloid nummularine has been isolated from the leaves of Berberis nummularia. On the basis of a study of its spectral characteristics (PMR, iR, and mass spectra), the structure of mmmmlarine has been established as 6-hydroxy-N-(3'-hydroxy-4'-methoxybenzyl)-7-methoxy-1-methyltetrahydroisoquinoline. Continuing an investigation of alkaloids of plants of the Berberis genus, we have studied the alkaloid composition of the leaves of B. nurmnu/an'a gathered in the Naukatskii region of the Oshskaya oblast in the phase of incipient fruit formation. We have previously isolated a number of new alkaloids in an investigation of the epigeal organs of this plant [3,4].By chloroform extraction of the leaves we obtained 0.24% of total alkaloids. The chromatography of this material on a column of silica gel led to the isolation of noroxyhydrastinine, glaucine, isoboldine, corypalline, oxyacanthine, isocorydine, obaberine, aromoline, and berbamnnine, and the new base nummularine (1). The known alkaloids were identified from their spectral characteristics and also by comparison with authentic specimens.Nummularine is an optically active crystalline base with the composition C19I-I23NO 4. Its UV spectrum showed the maximum in the 284 nm region that is characteristic for tetrahydroisoquinolines. The mass spectrum revealed peaks of ions with m/z 329 (M+), 314 (M -15), 192, 178, 137 (100%). The mass-spectral fragmentation of nummularine under electron impact was characteristic for alkaloids of the 1-methyl-N-benzylisoquinoline series [3,4]. The appearance of an ion with m/z 314 (M -15) showed the presence of a methyl substituent at C-l, and that of an ion with m/z 192 and of the maximum ion with m/z 137 showed that there are methoxy and hydroxy substiments in rings A and C.The methylation of (1) with diazomethane gave the O,O-dimethyl ether (2), identical, according to TLC and its IR spectrum, with O-methylberuumicine [3]. The passage to O-methylbernumicine showed that the substiments in rings A and C occupy the 6,7-and 3',4'-positions.The PMR spectrum of nummularine (1) showed four one-proton multiplets at 2.75, 3.25, 2.88, and 2.96 ppm, which are characteristic for the protons of the interconnected methylene groups of tetrahydroisoquinoline alkaloids, two one-proton doublets at 3.76 and 3.87 ppm with the SSCC J = 13.0 Hz, a three-proton doublet at 1.55 ppm (J = 6.5 Hz), a one-proton quartet at 3.96 ppm (J = 6.5) Hz, and two singlets from the protons of methoxy groups at 3.98 and 4.03 ppm in the aliphatic part of the spectrum.

μ Opioid receptor: novel antagonists and structural modeling

“…Several other analogues of 4 have been isolated from various Berberis species, however, no information is available concerning their activities at the MOR. We investigated nummularine 39 , bernumidine, bernumicine 40 , and bernumine 41 , amenurine, and O -acetylamenurine 42 within our docking workflow, respectively. Our results predicted an agonist MOR activity for bernumine, amenurine, and O -acetylamenurine.…”

“…Further investigations are therefore required to elucidate the mechanisms underlying the effects of Berberis vulgaris extracts and to identify the active constituents. Additionally, Berberis nummularia 39 40 41 and Berberis amurensis 42 containing nummularine 39 , bernumidine, bernumicine 40 , bernumine 41 , amenurine, and O -acetylamenurine 42 would be particularly interesting for further investigations. Thus, despite the low binding affinity at the MOR, the molecules identified as MOR ligands in this study represent an interesting starting point for further chemical optimization due to their structural novelty.…”

Phytopharmacology and Clinical Updates of Berberis Species Against Diabetes and Other Metabolic Diseases

“…Root, fruit Oxycanthine, berbamine, jatrorrhizine, palmatine, berberine Bernumine bernumidine and bernumicine, nummularine (Karimov et al, 1993d;Faskhutdinov et al, 1997)…”

Investigating functional properties of barberry species: an overview

“…Also, chlorogenic acid shows a relatively high amount in different species, 28 which indicates the antioxidant properties of this part of the plant. Berberis horrida Patagonine, pakistanamine, berberine, calafatine, berberine, -allocryptopine 51 Berberis densiflora Oxyacanthine, glaucine, O-methylcorypalline thalicmidine, isocorydine, densinine, densiberine 52 Berberis turcomanica Glaucine, thalicmidine, isocorydine, oxyacanthine, berberine, armepavine, N-methylcorydaldine, turcomanidine 53 Berberis nummularia Noroxyhydrastinine glaucine, isoboldine, corypalline, obaberine, isocorydine, aromoline, berbamunine, nummularine, oxyacanthine 54 Berberis valdiviana thalifoline, corypalline, methylcorypalline, jatrorrhizine, (−)-natalinine, (−)-natalamine, scoulerine, nandinine, reticuline, armepavine N-methylcorydaldine, polycarpine, N-methylcoclaurine, 8-oxyberberine, isotetrandine, obaberine, protopine, puntarenine, syringaresinol, (+)-isoboldine, porveniramine 55 Berberis thunbergii Thalicmidine, oxyacanthine, berberine, isocorydine, heliamine 40 Berberis virgetorum Jatrorrhizine, noroxyhydrastinine, (−)-berbervirine 41 Berberis koreana Berberine, palmitine, oxyacanthanine, berbamine 56…”