Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596757
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Four new diterpenoid alkaloids from Aconitum japonicum

K Wada
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
K Takeda
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
M Haraguchi
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
Y Abe
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
N Kuwahara
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
S Suzuki
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
A Terui
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
T Masaka
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
N Munakata
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
M Uchida
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
M Nunokawa
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
H Yamashita
1   Medicinal Chemistry, School of Pharmacy, Hokkaido Pharmaceutical University, 7 – 15 – 4-1, Maeda, Teine, Sapporo 006 – 8590, Japan
,
M Goto
2   Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7568, USA
,
KH Lee
2   Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7568, USA
3   Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

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The constituents of Aconitum japonicum THUNB (Ranunculaceae) were investigated many years ago, and the isolation and structure elucidation of twenty-three diterpenoid alkaloids from rhizomes of Aconitum species have been reported [1 – 7]. The investigation on the constituents of this plant have now resulted in the isolation of four new C19-diterpenoid alkaloids, 14-anisoyl-N-deethylaconine (1), N-deethylaljesaconitine A (2), 14-anisoyllasianine (3), and N-deethylnevadensine (4), together with fifteen known C19-diterpenoid alkaloids. Alkaloids were isolated using standard column liquid chromatography and structures assigned by high resolution mass spectrometry combined with C13 and 1 and 2D proton NMR spectroscopy. Two of the new C19-diterpenoid alkaloids (2, 4) and three of the known diterpenoid alkaloids (aconine 5, virescenine 6, ryosenamine 7) were evaluated for cytotoxic activity against four human tumor cell lines [lung carcinoma (A549), triple-negative breast cancer (estrogen and progesterone receptors-negative/HER2-negative) (MDA-MB-231), nasopharyngeal (KB), and multidrug resistant KB subline expressing P-glycoprotein (KB-VIN)]. However, the five diterpenoid alkaloids (2, 4-7) were inactive (IC50 > 40µM) against four human tumor cell lines (A549, MDA-MB-231, KB, and KB-VIN). The presentation describes the isolation of four new aconitine- or lycoctonine-type C19-diterpenoid alkaloids (1-4) from the rhizomes of A. japonicum. The structures of 1-4 were elucidated from 1D and 2D NMR spectroscopic data. The structure of three new alkaloids, 14-anisoyl-N-deethylaconine (1), N-deethylaljesaconitine A (2), and N-deethylnevadensine (4), was unusual N-deethyl C19-diterpenoid alkaloids. 14-Anisoyllasianine (3) was the fourth natural C19-diterpenoid alkaloid possessing the amino group at C-8. Lipoaconitine, lipomesaconitine, aconine (5), 15α-hydroxyneoline, isotalatizidine, nevadenine, talatisamine, virescenine (6), nevadensine, ryosenamine (7), and dehydrolucidusculine were isolated the first time from this plant.

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Keywords: Aconitum japonicum, C19-diterpenoid alkaloid, 14-anisoyl-N-deethylaconine, N-deethylaljesaconitine A, 14-anisoyllasianine, N-deethylnevadensine.

References:

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