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.

Two New C_(19)-Diterpenoid Alkaloids from Delphinium davidii Franch

Two new C19-diterpenoid alkaloids, davidisines A （1） and B （2） along with thirteen known alkaloids were isolated from the whole herb of Delphinium davidii Franch. Their structures were established by spectral methods, especially 2D NMR techniques.

Three new C_(19)-diterpenoid alkaloids from Delphinium laxicymosum var. pilostachyum

Three new lycoctonine-type C19-diterpenoid alkaloids, laxicymine 1, laxicymisine 2, and laxicyminine 3 have been isolated from the whole herb of Delphinium laxicymosum var. pilostachyum W.T. Wang. Their structures were established by spectra data.

Two novel aconane-type diterpenes derived from C-nor-C_(19)-diterpenoid alkaloid

Two novel C-nor-B-homo aconane-type diterpenes 4 and 5, featuring a unique eight-membered ring system, were obtained by the treatment of C-nor-C19-diterpenoid alkaloid 3 with HNO2 in 8% and 21% yields, respectively. Structures of these two compounds were established based on the combination of spectroscopic data, including HRESIMS, 1D and 2D NMR data. A olausible mechanism for the formation of 4 and 5 is also presented.

Three new C_(20)-diterpenoid alkaloids from Delphinium anthriscifolium var.savatieri

Three new C20-diterpenoid alkaloids, designated as anthriscifolmines A-C （1-3）, together with two known alkaloids denudatine and delgramine, were isolated from the whole herb of Delphinium anthriscifolium var. savatieri. The structures of these new alkaloids were elucidated on the basis of spectral data.

直缘乌头中新的C_(19)-二萜生物碱的结构研究

从直缘乌头 (AconitumtranssectumDiels .)根中分离得到 4个新的乌头碱型C19- 二萜生物碱 .由光谱法 (IR ,1HNMR ,13 CNMR ,2D NMR ,MS)确定其结构为 :8 O 乙基滇乌碱 (8 O ethylyunaconitine) (1)、去氮乙基查斯曼宁 (N deethylchasmanine) (2 )、直缘乌碱丁 (transconitineD) (3 )和直缘乌碱戊 (transconitineE) (4 ) .

C_(19)-二萜生物碱贡乌生的结构研究

Silica gel chromatography was adopted during the further study on the roots of Aconitum liljestrandii Hand Mazz and led to isolating a new C 19 dierpenoid alkaloid liljestrandisine(1). Its structure was established on the basis of spectral methods 2D NMR( 1H 1H COSY, HMQC, HMBC). Liljestrandisine was the second naturally occurring aconitine type diterpenoid alkaloid with an 16 α OH.

丽江紫乌头中一种新型C-19二萜生物碱的单晶结构解析

本实验对丽江紫乌头中的二萜生物碱进行研究,利用反复硅胶柱层析、重结晶等分离手段,从中分离得到一种新型C-19二萜生物碱,利用溶剂缓慢挥发法得到单晶并对其进行结构解析,通过CCDC数据库查询为一新型晶体结构,CCDC:2007957。

若干非天然产C_(19)-二萜生物碱的结构及其核磁共振谱的研究

根据光谱分析确定了16个非天然产二萜生物碱1-16的结构。指定了化合物1-9、12-16的氢谱和1-10、12-14的碳谱。有趣的是N-氧化物8在乙酰氯(-5℃,2日)作用下生成去氮乙基化合物15。讨论了化合物12-16形成的可能反应机理。

天然C_(19)-二萜生物碱的研究进展及其核磁共振波谱特征

C_(19)-二萜生物碱是二萜生物碱中数量最多的一类,主要分布于毛茛科的乌头属、翠雀属和飞燕草属植物中.C_(19)-二萜生物碱结构复杂、生理活性显著,一直吸引着科研工作者的广泛关注.本文主要对2010～2018年报道的天然来源C_(19)-二萜生物碱的研究进行总结,并归纳了C_(19)-二萜生物碱各子类型的核磁共振(NMR)结构特征和解析方式,以期为C_(19)-二萜生物碱的深入研究及开发提供参考依据.

Two New C19-Diterpenoid Alkaloids with Anti-inflammatory Activity from Aconitum iochanicum

Two new C ig-diterpenoid alkaloids, 7,8-epoxy-franchetine （1） and N（19）-en-austroconitine A （2）, were isolated from Aconitum iochanicum. Compound 1 was a new C19-diterpenoid alkaloid with a 7,8-epoxy unit. Their structures were elucidated by comprehensive spectroscopic analyses including UV, IR, MS, 1D and 2D NMR. Biological ac- tivity tests indicated that two new compounds exhibited inhibitory activity against nitric oxide （NO） production in LPS-activated RAW264.7 macrophages. Compared with positive control, the two new compounds showed weak an- ti-inflammatory effects with the inhibition rate of 27.3% and 29.2%, respectively.

New C_(19)-Diterpenoid Alkaloids from the Roots of Delphinium Giraldii

Three new C19-diterpenoid alkaloids, giraldines A (1), B (3) and C (4), were isolated from the roots of Delphinium giraldii Diels, together with three known C19-diterpenoid alkaloids, di-hydrogadesine (5), tatsiensine (6) and siwanine A (7), as well as their structures were elucidated by chemical evidence and spectral analyses, including IR, MS, 1D NMR and 2D NMR.

C_(19)-Diterpenoid alkaloid arabinosides from an aqueous extract of the lateral root of Aconitum carmichaelii and their analgesic activities

Eight new C_(19)-diterpenoid alkaloid arabinosides, named aconicarmichosides E–L(1–8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii(Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds 1–8, together with the previously reported four neoline 14-O-arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg(i.p.), as compared with the black control, compounds 1, 2, and 4–6 exhibited analgesic effects with 465.6% inhibitions against acetic acid-induced writhing of mice. Structure–activity relationship was also discussed.

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.

Efficient synthesis of the C/D rings of atisine-type C_(20)-diterpenoid alkaloids

A bicyclo[2.2.2]octane C/D ring system, with a lactonic ring at C-8 and C-9, of the atisine-type C20-diterpenoid alkaloids, was successfully synthesized, using an oxidative dearomatization/intramolecular Diels-Alder reaction.

Napelline-type C_(20)-diterpenoid alkaloid iminiums from an aqueous extract of ‘‘fu zi'': Solvent-/base-/acid-dependent transformation and equilibration between alcohol iminium and aza acetal forms

Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates（1 and 2） and aconicarmichinium C chloride（3）,were isolated from an aqueous extract of ＂fu zi＂,the lateral roots of Aconitum carmichaelii.Their structures were elucidated by extensive spectroscopic data analysis.Compounds 1-3 represent the first examples of napelline-type C20 diterpenoid alkaloid alcohol iminiums,of which the structures were fully characterized.In addition,transformation and equilibration between the alcohol iminiums（1-3） and the aza acetals la-3a were investigated by measurements of the NMR spectra in protic and aprotic deuterium solvents including alkali pyridine-d5,along with evaporation under reduced pressure and gradual additions of TFA,AcOH,and HC1.The results demonstrated that the transformation and equilibration were solvent-,base-,and acid-dependent.Especially,in aqueous biological fluid,these C20-diterpenoid alkaloids would more likely exist as the alcohol iminiums accompanied by anion counterparts in biosystems to increase their solubility, bioavailability, transportations, and functions.The absolute configurations of 1-3 were confirmed by X-ray crystallographic analysis of 2a.

Structure, property, biogenesis, and activity of diterpenoid alkaloids containing a sulfonic acid group from Aconitum carmichaelii

Three new C20-diterpenoid alkaloids with a sulfonic acid unit,named aconicarmisulfonines B and C(1 and 2)and chuanfusulfonine A(3),respectively,were isolated from the Aconitum carmichaelii lateral roots("fu zi"in Chinese).Structures of 1-3 were determined by spectroscopic data analysis.Intriguing chemical properties and reactions were observed for the C20-diterpenoid alkaloids:(a)specific selective nucleophilic addition of the carbonyl(C-12)in 1 with CD3 OD;(b)interconversion between 1 and 2 in D2 O;(c)stereo-and/or regioselective deuterations of H-11αin 1-3 and both H-11αand H-11βin aconicarmisulfonine A(4);(d)TMSP-2,2,3,3-d4 promoted cleavage of the C-12-C-13 bond of 4 in D2 O;(e)dehydrogenation of 4 in pyridine-d5,and(f)Na2 SO3-assisted dehydrogenation and N-deethylation of songorine(5,a putative precursor of 1-4).Biogenetically,1 and 2 are correlated with 4,for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements via migrations of C-13-C-16 and C-15-C-16 bonds of the napelline-type skeleton,respectively.Meanwhile,3 is a highly possible precursor or a concurrent product in the biosynthetic pathways of 1,2,and 4.In the acetic acid-induced mice writhing assay,at 1.0 mg/kg(i.p.),compounds 1,2,5,5 a,and 5 b exhibited analgesic effects against mice writhing.

Two New Diterpenoid Alkaloids from Spiraea japonica L. f. var.fortunei （Planchon） Rehd.

Abstract: Two new hetisine-type C20-diterpenoid alkaloids named spiraqine (1) and 6-hydroxylspiraqine (2), and four known alkaloids, namely spiredine (3), spiradine A (4), spiradine B (5), and spirasine V/VI (6), were isolated from Spiraea japonica L. f. var. fortunei(Planchon) Rehd. The structures of the alkaloids were elucidated using nuclear magnetic resonance analysis (1H-NMR, 13C-NMR, DEPT, HMQC, and HMBC) and mass spectrometry data.

中国乌头属植物药用亲缘学研究

毛茛科Ranunculaceae乌头属AconitumL.植物作为有毒植物及药用植物一直受到广泛的关注。本属全世界约有300余种,其中超过半数分布在中国。本文在总结乌头属二萜生物碱的化学分类及其分布、特征性二萜生物碱及其分类价值以及二萜生物碱的生源关系及其分类学意义的基础上,结合其毒性和疗效讨论了国产乌头属植物亲缘关系、化学成分和疗效及毒性之间的相关性,亦即药用亲缘学的初步研究。发现牛扁亚属subgen.Lycoctonum是以牛扁碱和C18-二萜生物碱为主的类群,由于其毒性中等,因而是寻找镇痛、抗炎等新药的一个对象。从二萜生物碱化学成分来看,露蕊乌头亚属subgen.Gymnaconitum并不显得最为进化,对其分类位置尚难作出最后的结论。乌头亚属subgen.Aconitum亚属下系之间的化学分类表现出如下特征:(1)唐古特乌头系ser.Tangutica和圆叶乌头系ser.Rotundifolia是以内酯型二萜生物碱为主的类群,毒性较小,是新药寻找的重点研究类群。保山乌头系ser.Bullatifolia以C20-二萜生物碱如光翠雀碱和宋果灵以及C19-二萜生物碱如乌头碱、滇乌碱和尼奥灵等为主。短柄乌头系ser.Brachypoda显示以3-乙酰乌头碱、乌头碱、伏乌碱等高度进化的乌头碱型二萜生物碱为主,胺醇类如尼奥灵次之,有时共存其他纳哌啉型C20-二萜生物碱的特征。准噶尔乌头系ser.Grandituberosa的化学特征是以高度进化的乌头碱型如乌头碱等和比较原始的胺醇如塔拉萨敏、尼奥灵等以及C20-二萜生物碱为主,均有较大毒性。褐紫乌头系ser.Brunnea则以C20-二萜生物碱如光翠雀碱和宋果灵为主,杂有高度进化的乌头碱型二萜生物碱如乌头碱等成分。化学分类上不支持其独立成为一个分支。以上各系组成乌头亚属的原始和中间过渡类群。其中唐古特乌头系和圆叶乌头系最为相近,褐紫乌头系可能是连接保山乌头系和短柄乌头系的“桥梁”,而准噶尔乌头系更靠近保山乌头系。(2)显柱乌头系ser.Stylosa是以含大茴香酸酯基的乌头碱型二萜生物碱以及塔拉萨敏和查斯曼宁胺醇类为主的类群,是块根较大的“大乌头”的主要来源,具有很大的毒性。兴安乌头系ser.Ambigua以含大茴香酸酯基的乌头碱型和原始胺醇类如塔拉萨敏、尼奥灵等二萜生物碱为主。蔓乌头系ser.Volubilia是以含大茴香酸酯基/苯甲酸酯基的乌头碱型和塔拉萨敏胺醇类以及高度进化的乌头碱型二萜生物碱为主的中间过渡类群。乌头系ser.Inflata以含15-羟基的单酯、双酯或多酯以及胺醇类乌头碱型二萜生物碱为主,且酯基中无大茴香酸酯基,此系是草乌的主要植物来源,具有很大的毒性,应十分慎用。这些系可能代表乌头亚属进化的类群。其中显柱乌头系与兴安乌头系可能较近缘。蔓乌头系可能是连接显柱乌头系/兴安乌头系与乌头系的中间类群。另外,保山乌头系、短柄乌头系和准噶尔乌头系可能是直接向显柱乌头系、蔓乌头系和乌头系过渡的较为原始的类群。(3)岩乌头系ser.Racemulosa从化学分类角度来看是一个特殊的类群,支持其独立成一个分支。其化学特征以牛扁碱型和乌头碱型的胺醇二萜生物碱如牛扁碱、异塔拉萨亭定和C20-二萜生物碱为主。如果单纯从化学成分来看,它与牛扁亚属植物似乎有一定关系。

附子化学成分和药理作用研究进展

通过查阅国内外文献,对附子的化学成分及药理作用进行了综述。结果表明:附子中主要含有生物碱成分,经分离鉴定的有百余个,主要骨架类型为C-19型二萜生物碱;其次为C-20型二萜生物碱,除生物碱以外,还含有黄酮、多糖、甾醇、有机酸等化学成分。附子的药理作用研究已久,主要有对心血管的作用、镇痛抗炎作用、免疫调节作用、抗肿瘤作用、抗衰老作用、降低胆固醇作用等。附子有"回阳救逆第一品药"之称,为广泛应用的有毒中药,目前临床观测附子毒副反应的项目及其标准既不系统,也不明确,还没有实用的指南对其进行安全性监控。对附子的化学成分和药理作用进行全面系统地整理,期待在转化研究的启发下,运用代谢组学等新技术为附子应用的安全性评价带来突破,使其能更好地服务于临床。