A New Alkaloid from the Roots of Aconitum carmichaeli Debx.

A new diterpene alkaloid, 12‐epi‐15‐O‐acetyl‐17‐benzoyl‐16‐hydroxy‐16,17‐dihydronapelline ( 1 ), along with nine known diterpene alkaloids including yunaconitine ( 2 ), neoline ( 3 ), mesaconitine ( 4 ), beiwutine ( 5 ), chasmanine ( 6 ), songorine ( 7 ), 12‐epi‐napelline ( 8 ), foresticine ( 9 ), and 15α‐hydroxyneoline ( 10 ) were isolated from the roots of Aconitum carmichaeli Debx. The structure of compound 1 was elucidated by comprehensive spectroscopic analysis.     

Two unique C21-diterpenoid alkaloids from Aconitum carmichaelii

Two sulfonated diterpenoid alkaloids possessing different but related novel carbon skeletons, named aconidenusulfonine A (1) and 12,16-secoaconidenusulfonine A (2), respectively, were isolated as minor components from an aqueous extract of the lateral roots of Aconitum carmichaelii (“Fu Zi”). The structures of 1 and 2, representing the first two C₂₁-diterpenoid alkaloids from nature, were determined by analysis of various spectroscopic data and chemical transformation, of which 1 was further proved by single-crystal X-ray diffraction. Especially, 1 exhibited dose-depended analgesic activity consistent with the clinical function of Fu Zi.     

New C19-diterpenoid alkaloids from the parent roots of Aconitum carmichaelii

Aconitum carmichaelii is a widely used traditional Chinese medicine and important source of clinical drugs. The parent roots of A. carmichaelii were investigated resulting in the isolation and identification of five new C₁₉-diterpenoid alkaloids; 14α-benzoyloxy-N-ethyl-15α-hydroxy-1α,6α,8β,16β,18-pentamethoxyaconitane formate (1), 14α-benzoyloxy-8β-butoxy-N-ethyl-13β,15α-dihydroxy-1α,6α,16β,18-tetramethoxyaconitane formate (2), 14α-benzoyloxy-8β-butoxy-N-ethyl-3α,13β,15α-trihydroxy-1α,6α,16β,18-tetramethoxylaconitane (3), 14α-benzoyloxy-8β-butoxy-3α,13β,15α-trihydroxy-1α,6α,16β,18-tetramethoxyl-N-methylaconitane (4) and 8β,14α-dibenzoyloxy-N-ethyl-13β,15α-dihydroxy-1α,6α,16β,18-tetramethoxyaconitane (5).     

膝瓣乌头根中新去甲二萜生物碱的结构研究

从膝瓣乌头(AconitumgeniculatumFlectcher)根中分得3个新的乌头碱型去甲二萜生物碱。由光谱法(^1HNMR,^1^3CNMR和MS)确定其结构为膝乌宁碱甲(genicunineA)1,膝乌宁碱乙(genicunineB)2,膝乌宁碱丙(genicunineC)3。     

Daphniphyllum alkaloids with cytotoxic activity from Daphniphyllum angustifolium

A new Daphniphyllum alkaloid, daphnezomine W (1), together with four known ones, were isolated from the stems of Daphniphyllum angustifolium Hutch. Their structures were elucidated by spectroscopic methods and comparing with the literature data. Compound 1 was a new daphnezomine L-type alkaloid and exhibited moderate cytotoxic activity against Hela cell line with IC₅₀ of 16.0 μg/mL. A plausible biosynthetic pathway of 1 was also proposed.     

Two new C18-norditerpenoid alkaloids from Aconitum delavayi

Further phytochemical investigation of the unique C18-norditerpenoid alkaloids from the roots of Aconitum delavayi Franch ledto the isolation of two new norditerpenoid alkaloids,delavaconitine F 1 and delavaconitine G 2.Their structures were determinedfrom spectroscopic evidence.     

New C20-diterpenoid alkaloids from Aconitum sinomontanum

Two new denudatine-type C₂₀-diterpenoid alkaloids, named sinomontanidines A (1) and B (2), were isolated from the roots of Aconitum sinomontanum Nakai. Their structures were elucidated by extensive analysis of 1D, 2D NMR, and MS data.     

Comprehensive quality evaluation of the lateral root of Aconitum carmichaelii Debx. (Fuzi): Simultaneous determination of nine alkaloids and chemical fingerprinting coupled with chemometric analysis

Amino alcohol alkaloids are the active components in the lateral root of Aconitum carmichaelii Debx. (Fuzi), and they have a variety of pharmacological activities. However, the chemical fingerprints of the ester alkaloids reported to date were mainly obtained from high‐performance liquid chromatography coupled with ultraviolet detection, and it is difficult to obtain information about amino alcohol alkaloids in Fuzi from such chromatograms. In this paper, a comprehensive fingerprinting method was established using high‐performance liquid chromatography coupled with an evaporative light‐scattering detector for the simultaneous quantitative analysis of both the amino alcohol alkaloids and ester alkaloids. A total of 42 samples of Fuzi from four production areas were analyzed by constructing high‐performance liquid chromatography fingerprints. Then, the quantitative results of the chemical fingerprints combined with chemometrics methods were employed to reveal the factors affecting the geo‐authentic Fuzi and to determine characteristic components that can be used to identify these samples. The results indicated distinct differences in the alkaloid contents among samples from the four regions; the geographical origin may be the primary factor affecting the geo‐authentic Fuzi, and 15 major components (including songorine, neoline, and hypaconitine, which were quantitatively determined) were found to be characteristic components for the discrimination of Fuzi samples from various regions. Neoline might be a critical component for identifying geo‐authentic Fuzi. This approach is convenient, reproducible and provides a promising method for the quality evaluation of Fuzi.     

Synthetic study of hetisine-type aconite alkaloids. Part 2: Preparation of hexacyclic compound lacking the C-ring of the hetisan skeleton

A hexacyclic compound 1, having almost the full hetisine-type aconite alkaloid framework lacking only the C-ring with an exo-methylene group, was synthesized from the intermediate 3 reported in the preceding paper. The synthesis involved the following key reactions the crucial conversion of 3 to 4, a stereoselective hydrocyanation reaction to obtain 5 from 4, and construction of the azabicyclic ring system (5→1).     

Discovery of Hyrtinadine A and Its Derivatives as Novel Antiviral and Anti-Phytopathogenic-Fungus Agents

Plant diseases caused by viruses and fungi have a serious impact on the quality and yield of crops, endangering food security. The use of new, green, and efficient pesticides is an important strategy to increase crop output and deal with the food crisis. Ideally, the best pesticide innovation strategy is to find and use active compounds from natural products. Here, we took the marine natural product hyrtinadine A as the lead compound, and designed, synthesized, and systematically investigated a series of its derivatives for their antiviral and antifungal activities. Compound 8a was found to have excellent antiviral activity against the tobacco mosaic virus (TMV) (inactivation inhibitory effect of 55%/500 μg/mL and 19%/100 μg/mL, curative inhibitory effect of 52%/500 μg/mL and 22%/100 μg/mL, and protection inhibitory effect of 57%/500 μg/mL and 26%/100 μg/mL) and emerged as a novel antiviral candidate. These compound derivatives displayed broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi at 50 μg/mL and the antifungal activities of compounds 5c, 5g, 6a, and 6e against Rhizoctonia cerealis are higher than that of the commercial fungicide chlorothalonil. Therefore, this study could lay a foundation for the application of hyrtinadine A derivatives in plant protection.     

Two new C_(19)-diterpenoid alkaloids from roots Aconitum hemsleyanium var. atropurpureum

A new franchetine-type C19-diterpenoid alkaloid 3-hydroxyfranchetine 1 and a new aconitine-type C19-diterpenoid alkaloid atropurpursine 2 have been isolated from the roots of Aconitum hemsleyanium var. atropurpureum. The structures of these new alkaloids were established on the basis of spectral data.     

Antileishmanial diterpenoid alkaloids from Aconitum spicatum (Bruhl) Stapf

The crude extracts of tubers of Aconitum spicatum (Bruhl) Stapf were investigated for in vitro antileishmanial activity against Leishmania major. The dichloromethane extract at pH 2.5 showed antileishmanial activity with IC₅₀ value of 27.10 ± 0.0 μg/mL. Chromatographic purification of the dichloromethane extract led to isolation of three C-19 norditerpenoid alkaloids indaconitine (1), chasmaconitine (2) and ludaconitine (3). Compounds 3 and 2 showed antileishmanial activity with IC₅₀ = 36.10 ± 3.4 and 56.30 ± 2.1 μg/mL, respectively. Compound 1 was less effective (IC₅₀ > 100 μg/mL). The cytotoxicity of compounds 1, 2 and 3 studied against MCF7, HeLa and PC3 cancer cell lines and 3T3 normal fibroblast cell line did not show cytotoxicity at 30 μM.     

Synthetic study of hetisine-type aconite alkaloids. Part 1: Preparation of tetracyclic intermediate containing the C14-C20 bond

Full details for the total synthesis of (±)-nominine, a hetisine-type aconite alkaloid, are presented in three parts. Here (part 1), we describe the preparation of the key tetracyclic intermediate 6. Our palladium-catalyzed intramolecular α-arylation was adopted for preparation of the intermediate 4 with an angular formyl group. An acetal-ene reaction was then employed for C14-C20 bond formation to secure 6 from 5. The reaction mechanism of the acetal-ene reaction is discussed, and a method for removal of the 2-hydroxyethyl group from 6 is developed.     

Microcalorimetric study on the bacteriostatic activity of isoquinoline alkaloids

The isoquinoline alkaloids were isolated from traditional Chinese drugs of Phellodendri Cortex, Radix Stephaniae Tetrandrae, Corydalis Yanhusuo and Corydalis Bungeana. The power-time curves of growth of E. coli at different concentrations of isoquinoline alkaloid at 37°C were determined by a 2277 Thermal Activity Monitor. The rate constant of bacteriostastic activity was calculated. The relationship between growth rate constant and concentration was established. The optimum bacteriostastic concentration was determined. Experimental results have indicated that all the isoquinoline alkaloids isolated from the four kinds of traditional Chinese drugs have bacteriostastic activity and the order is Phellodendri Cortex>Radix Stephaniae Tetrandrae>Corydalis Yanhusuo>Corydalis Bungeana.     

Synthetic study of hetisine-type aconite alkaloids. Part 3: Total synthesis of (±)-nominine

Completion of the total synthesis of (±)-nominine (1) is described in detail. Based on the results of the preceding two papers, total synthesis of (±)-nominine was accomplished diverging from the intermediate 7. Thus, following pyrrolidine ring formation through transformation from 7 to 8, the C-ring was constructed by radical cyclization to form 10 from the enyne precursor 9. Subsequent elaboration of the C-ring, followed by formation of the azabicyclic ring system, completed a total synthesis of (±)-1. Single-crystal X-ray analysis of (±)-1 unambiguously confirmed its molecular structure and racemic crystal structure.     

Antiviral properties from plants of the Mediterranean flora

Natural products are a successful source in drug discovery, playing a significant role in maintaining human health. We investigated the in vitro cytotoxicity and antiviral activity of extracts from 18 traditionally used Mediterranean plants. Noteworthy antiviral activity was found in the extract obtained from the branches of Daphne gnidium L. against human immunodeficiency virus type-1 (EC₅₀ = 0.08 μg/mL) and coxsackievirus B5 (EC₅₀ = 0.10 μg/mL). Other relevant activities were found against BVDV, YFV, Sb-1, RSV and HSV-1. Interestingly, extracts from Artemisia arborescens L. and Rubus ulmifolius Schott, as well as those from D. gnidium L., showed activities against two different viruses. This extensive antiviral screening allowed us to identify attractive activities, offering opportunities to develop lead compounds with a great pharmaceutical potential.     

Chemical UPLC‐ESI‐MS/MS profiling of aconitum alkaloids and their metabolites in rat plasma and urine after oral administration of Aconitum carmichaelii Debx. Root extract

In this paper, an ultra high performance liquid chromatography tandem mass spectrometric (UPLC‐ESI‐MS/MS) method in positive ion mode was established to systematically identify and to compare the major aconitum alkaloids and their metabolites in rat plasma and urine after oral administration of Fuzi extract. A total twenty‐nine components including twenty‐five C19‐diterpenoid alkaloids and four C20‐diterpenoid alkaloids were identified in Fuzi extract. Thirteen of the parent components and five metabolites were detected in rat plasma and sixteen parent compounds and six metabolites in urine. These parent components found in rat plasma and urine were mainly C19‐diterpenoid alkaloids. All of the metabolites in vivo were demethylated metabolites (phase I metabolites), which suggested that demethylation was the major metabolic pathway of aconitum alkaloids in vivo. A comparison of the parent components in rat plasma and urine revealed that 3‐deoxyacontine was found in plasma but not in urine, while kalacolidine, senbusine and 16‐β‐hydroxycardiopetaline existed in urine but not in plasma, which indicated that most alkaloids components were disposed and excreted in prototype form. This research provides some important information for further metabolic investigations of Fuzi in vivo.     

Two New C20‐Diterpenoid Alkaloids from Aconitum carmichaelii

Two new C₂₀‐diterpenoid alkaloids, named aconicarchamines A and B ( 1 and 2 , resp.), were isolated from Aconitum carmichaelii. By UV, IR, MS, and 1D‐ and 2D‐NMR analyses, their structures were elucidated as 14,17‐dihydro‐14,17‐dihydroxyajabicine and 15‐O‐acetyllassiocarpine. Compound 1 is the third C₂₀‐diterpenoid alkaloid with the lycoctine skeleton bearing an exocyclic C‐atom at C(14).     

黄草乌中的新二萜生物碱

从黄草乌(Aconitum vilmorinianum Kom.)根中分离得到三个新C~1~9-二萜生物碱: 黄乌宁(vilmorinine, 1), 黄乌生(vilmorisine20和黄乌亭(vilmoritine, 3)。采用波谱分析及化学方法确定了它们的结构。