Isorugosiformins A–F, six ent-kaurane diterpenoids from Isodon rugosiformis

doi:10.1016/j.fitote.2020.104529

Fitoterapia

Volume 142, April 2020, 104529

https://doi.org/10.1016/j.fitote.2020.104529 Get rights and content

Abstract

Six new ent-kaurane diterpenoids, isorugosiformins A–F (1–6), were isolated from the aerial parts of Isodon rugosiformis Hand.-Mazz. Hara. Their structures were elucidated by spectroscopic data interpretation, single crystal X-ray diffraction, and quantum chemical calculation of NMR parameters. The absolute configuration of 5 as 6R was the first case in the known 6,7:8,15-diseco-7,20-olide-6,8-cyclo-ent-kaurane diterpenoids.

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 [δ_H 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 [δ_H 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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Isorugosiformins A–F, six ent-kaurane diterpenoids from Isodon rugosiformis

Abstract

Graphical abstract

Introduction

Section snippets

General experimental procedures

Results and discussion

Conclusion

Declaration of Competing Interest

Acknowledgements

Nat. Prod. Rep.

Tetrahedron

Tetrahedron

Phytochemistry

Tetrahedron

Diterpenoids from Isodon species and their biological activities

Nat. Prod. Rep.

11-step total synthesis of (−)-maoecrystal V

J. Am. Chem. Soc.

A symmetric total synthesis of (−)-maoecrystal V

Chem. Asian J.

Enantioselective synthesis of (–)-maoecrystal V by enantiodetermining C-H functionalization

J. Am. Chem. Soc.

Enantioselective total synthesis of (−)-maoecrystal V

J. Am. Chem. Soc.

Total synthesis of maoecrystal V: early-stage C-H functionalization and lactone assembly by radical cyclization

J. Am. Chem. Soc.

Total synthesis of (+/−) maoecrystal V

J. Am. Chem. Soc.

Total synthesis of (+/−) maoecrystal V

J. Am. Chem. Soc.

A concise total synthesis of (−)-maoecrystal Z

J. Am. Chem. Soc.