Isorugosiformins A–F, six ent-kaurane diterpenoids from Isodon rugosiformis
Graphical abstract
Introduction
The genus Isodon, which consists of approximately 150 species of under-shrubs, sub-under shrubs, or perennial herbs, is mainly distributed in tropical and subtropical Asia [1]. Phytochemical investigations on Isodon species during the past decades have led to the discovery of more than 1200 diterpenoids, and most of them possess fascinating skeletons and a broad spectrum of biological activities [1,2]. Among them, 6,7-seco-ent-kauranes represent an interesting class of highly oxygenated diterpenoids with complicated cyclic connectivity, highly congested framework, and multiple stereocenters [3]. Due to the intriguing structures and interesting biological activities, many 6,7-seco-ent-kauranes, such as maoecrystal V [[4], [5], [6], [7], [8], [9], [10]], maoecrystal Z [[11], [12], [13]], trichorabdal A [[12], [13], [14]], longikaurin E [13,14] and sculponeatin N [15,16] have been totally synthesized. As a continuous endeavor to explore the structural and bioactive diversity of 6,7-seco-ent-kauranoids from Isodon species, phytochemical investigation was undertaken for the first time on I. rugosiformis Hand.-Mazz. Hara collected from Weixi County in Yunnan Province. As a result, six previously unreported ent-kaurane diterpenoids, isorugosiformins A–F (1–6), were isolated from the aerial parts of I. rugosiformis. Interestingly, they possessed rare 6,7:8,15-diseco-7,20-olide-6,8-cyclo-ent-kaurane scaffolds (Fig. 1), which has only six natural precedents, namely maoecrystal Z [17], hikiokoshin B [18] and ternifoliusins A–D [19]. Herein, the isolation, structure elucidation, and bio-evaluation of these compounds are described.
Section snippets
General experimental procedures
Melting points were obtained on an XRC-1 apparatus and were uncorrected. IR spectra were obtained on a Nicolet iS10 FT-IR spectrometer with KBr pellets. UV spectra were recorded on a Shimadzu UV-2700 spectrophotometer. Optical rotations were measured on Autopol VI, Seiral #91058. Experimental ECD spectra were measured on a Chirascan instrument. HRESIMS data were acquired on an Agilent 6540 QSTAR TOF time-of-flight mass spectrometer. NMR spectra were performed on Bruker DRX-500 and Bruker
Results and discussion
Isorugosiformin A (1) was isolated as colorless crystals (MeOH). A molecular formula of C24H36O9 was determined from HRESIMS m/z 491.2263 [M + Na]+ (calcd for C24H36O9Na+, 491.2252), requiring seven degrees of unsaturation. Its 1H NMR data (Table 1) showed signals of five methyl groups [δH 1.11 (s, H3–19), 1.21 (s, H3–18), 2.18 (s, OAc-1), 3.60 (s, OMe-15), and 3.17 (s, OMe-17)], four oxymethylene protons [δH 3.82 (t, 9.3 Hz, H-17a), 3.62 (overlap, H-17b) and 4.90 (overlap, H-20)], three
Conclusion
Isorugosiformins A–F (1–6), six new 6,7:8,15-diseco-7,20-olide-6,8-cyclo-ent-kaurane diterpenoids, were isolated from the aerial parts of Isodon rugosiformis Hand.-Mazz. Hara. And 5 represented the first case of the frameworks with the configuration of 6R, in which quantum chemical calculations was successfully applied.
Declaration of Competing Interest
None.
Acknowledgements
We thank Service Center for Bioactivity Screening, State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany for bioassays. This project was supported financially by the National Natural Science Foundation of China (Grants 81673329 and 81903520).
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Structurally diverse diterpenoids from Isodon oresbius and their bioactivity
2022, Bioorganic ChemistryCitation Excerpt :Thus, 12 was determined as 4S-11-hydroxy-8,11,13-abietatrien-18-oic acid. The structures of the known compounds were determined by comparing their spectroscopic data to literature values, which were identified as isodonal (13) [22,23], lambertic acid (14) [25], lushanrubecebsins F and I [26], shikokianin [27], hikiokoshin B [28], isorugosiformin A [29], isoadenolin J [30], hypoglicin A [31], ent-kaurane-3β,16β-diol [32,33], (–)-16α-hydroxykauran-19-oic acid [34], epinodosinol [35], lasiodonin [36,37], laxiflorin G [38], 6α,15α-dihydroxy-20-aldehyde-6,7-seco-6,11α-epoxy-ent-kaur-16-en-1,7-olide [39], 15α-hydroxy-6β-methoxy-6,7-seco-6,20-epoxy-ent-kaur-16-en-1,7-olide [40], sculponin N [41], effusanins A and E [42], isorosthin L [43], lasiokaurin [44], parvifolines H–J, adenolin E [45], isojaponin A [46], laxiflorolide S [47], and isodoternifolin B [48]. ent-Kauranoids containing α,β-unsaturated ketone groups from Isodon species were well known for their cytotoxicity [1,2].