Isolation, Structure Elucidation, Semi-Synthesis, and Structural Modification of C₁₉-Diterpenoid Alkaloids from Aconitum apetalum and Their Neuroprotective Activities

Abstract

Five new aconitine-type C 19 -diterpenoid alkaloids, apetalrines A−E (1−5), were isolated from Aconitum apetalum. Their structures were determined by analysis of 1D and 2D NMR, IR, and HRESIMS data. Semisynthesis of apetalrine B (2) from its parent compound aconorine was achieved to confirm the structure proposed. Twenty derivatives of 2 (11a−11l, 12a, 12b, 12d, 12e, 12j, 12k, 12m, 12n) were synthesized via a unified approach relying on simple coupling reactions. The evaluation of neuroprotective effects of compounds (1−5, 11b, 11c, 11f−11i, 12a, 12b, 12d, 12e, 12k, 12m, 12n) with low cytotoxicity revealed compound 2 to exhibit good neuroprotective effects in H 2 O 2 -treated SH-SY5Y cells at a concentration of 50 μM. A series of studies using flow cytometry, staining, and Western blotting on 2 indicated that its neuroprotective effects may arise from inhibiting cell apoptosis.

Norditerpenoid alkaloids from Aconitum and Delphinium: structural relevance in medicine, toxicology, and metabolism

“…83 The latter afforded 5 apetalrines A–E based on N -acylated 2-aminobenzoyl esters and also structurally identified following detailed spectral analysis. 84 Ablajan et al reported 5 previously undescribed DA, barpuberudine and barpubesines A–D, and two interesting novel C18 NDA, barpubenines A–B, isolated from the whole plant of A. barbatum var. puberulum Ledeb.…”

Two New C18‐Diterpenoid Alkaloids from Aconitum leucostomum Worosch.

“…Nominine showed potent protective activity against MPP + ‐induced apoptosis in SH‐SY5Y cells [9] . Also, apetalrine B, an aconitine‐type C 19 ‐diterpenoid alkaloid isolated from A. apetalum , exhibited good neuroprotective effects in H 2 O 2 ‐treated SH‐SY5Y cells [10] …”

“…[9] Also, apetalrine B, an aconitine-type C 19 -diterpenoid alkaloid isolated from A. apetalum, exhibited good neuroprotective effects in H 2 O 2 -treated SH-SY5Y cells. [10] Aconitum leucostomum Worosch. (Ranunculaceae), which grows at altitudes 1400 -2550 m, is a perennial herb distributed in the Gansu province and Xinjiang Uygur Autonomous Region of China.…”

Three New C₁₉-Diterpenoid Alkaloids from <i>Aconitum novoluridum</i>

“…1) This kind of compounds have attracted considerable interest because of their complex structure, and noteworthy physiological effects. 2) As our ongoing interest in the phytochemical studies on the pharmacologically interesting plants Aconitum and Delphinium, we obtained a series of structurally and chemotaxonomically interesting diterpenoid alkaloids. [3][4][5][6][7] The plant Aconitum novoluridum Munz belongs to the Aconitum genus in the family of Ranunculaceae and is distributed in the northeast of Tibet in China, Bhutan, Nepal, and Sikkim at an attitude of 3800-4500 m. 8) Aconitum novoluridum is similar to Aconitum apetalum, but the stem is lower and thinner, the leaves are smaller, the bracteoles are ovate, the sepals are purplish-red, and the petals are distinguished by short spines.…”