The genus Papaver, which belongs to the family Papaveraceae, consists of approximately 110 annual, biennial, and perennial plants distributed in central and south-western Asia, central and southern Europe, and northern Africa. A variety of structurally diverse alkaloids such as benzylisioquinoline, morphinane, aporphine, protopine, and phthalideisoquinoline has been isolated from species of Papaveraceae. Of the genus Papaver, only the opium poppy (P. somniferum L.) and P. setigerum D. C. are able to produce the narcotic substances such as morphine, codeine and thebaine as their secondary metabolites. Although morphine is the most powerful pain-killer, it also has very strong addictive properties. For this reason, P. setigerum and P. somniferum are controlled as illegal opium poppy in Korea. In our previous study on unknown poppy from Jeju Island, it was identified as P. setigerum using by metabolite profiling and genetic methods. P. setigerum has been reported to contain various benzylisoquinoline, morphinane, and phthalideisoquinoline alkaloids. In this work, we have investigated the chemical constituents of the whole plants of P. setigerum. The present paper describes the isolation and structural characterization of a new rearranged phthalideisoquinoline alkaloid along with two known benzylisoquiline and a known phthalideisoquinoline alkaloids. The EtOAc-soluble fraction of the whole plants of P. setigerum was successively subjected to silica gel, C18, and semipreparative HPLC on ODS yielded a new alkaloid 1 together with three known compounds, papaverine (2), papaveraldine (3), and α-noscapine (4). Compound 1, tentatively named setigerumine I, was obtained as a light yellow amorphous powder and the UV absorption was appeared at 290 nm. The positive HRESIMS of 1 gave a [M+H] at m/z 428.1356 (calcd 428.1345), corresponding to the molecular formula C22H21NO8. The HNMR spectrum of 1 displayed a singlet aromatic proton (δH 6.41, ring A), a pair of ortho-coupled aromatic protons (δH 7.48 and 7.42, ring B), a -CH-CH-CH2group (δH 4.62, 3.86, 3.05, and 2.88), a methylenedioxy group (δH 5.87), three mothoxy groups (δH 4.05, 3.98, 3.66), and a N-methyl group (δH 2.86). The Cand DEPT NMR spectra of 1 yielded 22 carbon signals including those corresponding to a carbonyl carbon (δC 166.3), and a spiroketal carbon (δC 108.9). These H-, C, and DEPT NMR data indicated that 1 was closely similar with a rearranged phthalideisoquinoline alkaloid, dactylicapnosinine except for an additional methoxy group. The skeleton of rearranged phthalideisoquinoline alkaloid, consists of unique ring C, D with C-N-O-C, moieties, and the lactone ring E, was further clarified with H-H COSY and HMBC experiments. The five membered ring C was confirmed by -CH-CH-CH2correlation with HH COSY data. Moreover, the A-E ring system was assigned by the observed HMBC correlations from H-1 (δH 3.05, 2.88) to C-2, C-7, C-3a and C-7a, from H-3 (δH 4.62) to C3a and C-6', and from H-1' (δH 7.42) to C-α. The position of methoxy groups were established by HMBC correlations from three methoxy groups (δH 4.05, 3.98, 3.66) to C-4', C3', and C-4, respectively. Furthermore, methylenedioxy group (δH 5.87) was correlated with C-5, and C-6. The relative configuration of 1 was determined on the basis of coupling constant and NOESY experiment. The H-2 and H-3 was confirmed as cisand axial orientations by a comparison of coupling constant between H-2 and H-3 (J = 8.5 Hz), and the observed NOE correlations. In the NOESY spectrum, the cross peak was detected between H-3 and H-1', which is clearly indicated the relative configuration of C-α as shown in Figure 3. However, the optical rotation showed a zero value, it may be a racemate. This rearranged phthalideisoquinoline alkaloid is reported for the first time in the genus Papaveraceae.
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Apr 29, 2024
Hao Wang + 4
Open Access