Lycodine-Type Lycopodium Alkaloids from the Whole Plants of Huperzia serrata

t Three new lycodine-type Lycopodium alkaloids,namely 1-methyllycodine(1),8a-hydroxy-15,16-dehydro-desN-methyl-a-obscurine(2),N-methyl-16-hydroxyhuperzine B(3),and one new natural lycodine-type Lycopodium alkaloid,N-methylhuperzine A(4),along with 11 known analogues(5–15),were isolated from the whole plants of club moss Huperzia serrata.The structures of 1–4 were elucidated on the basis of NMR spectroscopic and mass spectrometry data.Among them,compound 1 was the first lycodine-type alkaloid possessing a methyl group at C-1.In addition,the structure of 5 was confirmed by the single-crystal X-ray crystallography data and its^(13)C NMR was reported for the first time in current study.Compounds 1–5 were tested their BACE1 inhibitory activity.

Carinatines A and B,Lycopodium Alkaloids from Phlegmariurus carinatus

Carinatine A(1),a C16N2-type Lycopodium alkaloid possessing a 5/6/6/6 ring system formed by a new C-4/C-12 bond,and carinatine B(2),the first derivative of lycojaponicumin C,along 16 known compounds,were isolated from the whole plant of Phlegmariurus carinatus.Their structures were elucidated based on the spectroscopic data.The two new isolates were no inhibitory activity for the acetylcholinesterase(AChE).

Lycoplanines B-D,Three Lycopodium Alkaloids from Lycopodium complanatum

A novel Ci7N Lycopodium alkaloid(LA),lycoplanine B(1),containing an unusual formyl group,along with two new LAs,lycoplanines C(2)and D(3),were isolated from the whole plant of Lycopodium complanatum.Their structures were elucidated by extensive NMR techniques,including 1D-and 2D-NMR experiments,as well as comparing their spectral data with those of the known analogues.A possible biogenetic pathway for 1 was also proposed.

Lyconadins G and H,Two Rare Lyconadin-Type Lycopodium Alkaloids from Lycopodium complanatum

Two rare lyconadin-type Lycopodium alkaloids,lyconadins G(1)and H(2),together with four known ones(3–6),were isolated from Lycopodium complanatum.The structures were determined on the basis of their spectroscopic analyses,and the absolute configuration of 1 was established by an X-ray crystallographic analysis.It is the first time to establish the absolute configuration of lyconadin-type Lycopodium alkaloid by an X-ray diffraction experiment.In addition,these findings may provide more information for the biosynthesis of lyconadins.

One-step synthesis of Lycopodium alkaloid(-)-huperzine W via Suzuki-Miyaura coupling

The first total synthesis of(-)-huperzine W(1)has been achieved.Key element of the synthesis is a highly convergent assemblage for the two rings system of target molecule utilizing an efficient Suzuki-Miyaura coupling reaction between chiral iodide 2 and 2-allylpyrrolidinone 4.Evaluation of the AchE inhibition of synthetic huperzine W was also carried out.

Carbonic anhydrase-like enzymes in the formation of Lycopodium alkaloid

Plant alkaloids,renowned for their structural diversity and bioactivity,are prominent in both modern and traditional medicine[1].Unraveling the intricacies of plant alkaloid biosynthesis could pave the way for the discovery of new natural products and pathways.It may also shed light on the roles of existing pathways in host biology and provide valuable tools for metabolic engineering in plants and microbes[2].Unlike other major classes of plant natural products,such as terpenoids and polyketides,the formation of alkaloid scaffolds does not conform to a uniform chemical theme or depend on a singular enzyme class[3].A case in point is the Lycopodium alkaloids in the Lycopodiaceae family,where the enzymes responsible for their core scaffold construction remain unidentified[4].

A new Lycopodium alkaloid from Phlegmariurus fargesii

AIM: To investigate the chemical constituents from the whole plants of Phlegmariurus fargesii. METHOD: Compounds were isolated by repeated silica gel column chromatography. Their structures were elucidated by spectroscopic methods and chemical correlation. The acetylcholinesterase(AChE) inhibitory activity of the isolated compounds was evaluated. RESULTS: A new Lycopodium alkaloid, lycopodine N-oxide(1), along with lycopodine(2), 8,15-dehydrolycopodine(3), 6α-hydroxylycopodine(4), deacetyllycoclavine(5), N-methylhuperzine B(6), lycodine(7), and phlegmarine(8), was isolated. CONCLUSION: Compound 1 is a new Lycopodium alkaloid, and compound 3 was obtained from nature for the first time. Other alkaloids are isolated from this plant for the first time.

Michael addition-based cyclization strategy in the total synthesis of Lycopodium alkaloids

Lycopodium alkaloids, a unique family of biologically important natural products isolated and characterized from various species of Lycopodium(sensu lato), have attracted extensive attention from chemists and pharmacists in the past three decades. Michael addition-based cyclization has been successfully employed as an elegant and efficient ring-construction protocol of constructing key cyclohexanone intermediates in the total synthesis of Lycopodium alkaloids. This mini-review chooses and summarizes several representative total syntheses of various Lycopodium alkaloids in which intramolecular Michael addition severed as the key methodology.

石松生物碱研究进展

本文综述了自1994年以来天然石松生物碱的研究进展和石杉碱甲的抗乙酰胆酯酶生物活性及它的构效关系研究。按照石松生物碱的分类方法,系统归纳了lycopodine,lycodine,fawcettimine和misceualleous四种类型生物碱的结构特点和内在的相互关系,以及各种类型的新天然化合物。石杉碱甲是由我国科学家首先发现的一个天然的石松生物碱,药理实验证明它是一个高选择性的乙酰胆碱酯酶抑制剂,具有口服生物利用度高、作用时间长、副反应小的特点,优于已上市的第一代治疗老年痴呆药物E2020,Tacrine,Physostigmine和Gslanthamine。已合成的大量的石杉碱甲类似物的药理实验表明,作为AChE抑制剂,石杉碱甲是一个紧凑的结构,现有的结构要素一个都不能少。不过,以天然石杉碱甲为原料合成的席夫碱衍生物和用石杉碱甲的结构片断与Tacrine相结合的类似物研究取得了可喜的进展。

石松类生物碱成分研究的新进展

石松生物碱结构多变且具有复杂的多环骨架,该类生物碱奇特的多环结构使其成为化学和生物合成研究的热点之一。我国科学家从民间草药蛇足石杉中分得具有强效、低毒、高选择性抑制乙酰胆碱酯酶活性的石杉碱甲,引起世界各国科学家的广泛注意。最近的关于石松生物碱的综述是由M a和Gang于2004年报道的,文章对1994到2004年间石松生物碱的研究进行了概括。其后又有从17种石松类植物中分离到84个新的石松生物碱报道,其中16个是骨架新颖的新生物碱。由此,文章对这些新生物碱的结构分类和生物活性进行了综述。

蛇足石杉中两个新的过氧羟基取代的石松生物碱(英文)

从我国民间中药蛇足石杉(Huperzia serrata (Thunb.)Trev.)的全草的总碱部位分得3个石松生物碱,经光谱分析鉴定为11α-过氧羟基马尾杉碱乙(1)、7-过氧羟基马尾杉碱乙(2)和马尾杉碱乙(3)。1和2为首次发现的过氧羟基取代的石松生物碱。

石松生物碱研究最新进展

石松生物碱是一类结构新颖的天然产物,其结构复杂多样、手性中心多、绝对构型多变和显著的生物活性,一直是研究的热点之一。从民间草药千层塔中分得具有强效、低毒、高选择性抑制乙酰胆碱酯酶活性的石杉碱甲,引起国内外许多学者的高度关注。迄今为止,发现和报道了300多种石松生物碱。本文旨在将近几年来发现和报道的80余种新生物碱的结构及其生物活性进行综述,以飨有兴趣的天然产物化学工作者。

石杉碱戊和石杉碱己的结构

在石杉［Ｈｕｐｅｒｚｉａｓｅｒｒａｔａ（Ｔｈｕｎｂ．）Ｔｒｅｖ．］中分得了命名为石杉碱成素和已素的２个新生物碱，并用２Ｄ－ＮＭＲ和ＭＳ测定了它们的化学结构．

几个石松类生物碱的质谱分析

采用电子轰击电离高分辨质谱及B/E联动扫描(Linked Scan)法,研究了Huperzine E,F,G三个lycopodine类新生物碱的质谱行为.并应用这些结果确定了另一个新生物碱Huperzine O的结构.

东北石杉生物碱成分的研究

从东北石杉中分离得到7个石松生物碱,通过NMR、MS及IR等光谱分析,分别鉴定为:luciduline(1),dithydroluciduline(2),lycodine(3),huperzine B(4),serratinine(5),serratidine(6),mecleanine(7)。这些化合物均为首次从该植物中分得。

伸筋草醇提工艺研究

目的:优选伸筋草总生物碱提取工艺。方法:以醇溶液的PH值、乙醇体积分数、提取时间、料液比为影响生物碱提取量的因素,采用L9(34)正交设计试验,以总生物碱为考察指标进行正交实验。结果:最佳工艺为pH值为3的30%乙醇,提取60min,提取料液比为1:10。结论:该提取工艺可用于伸筋草总生物碱的提取,并适用于工业化生产。

石松生物碱对东乡伊蚊幼虫体内乙酰胆碱酯酶活性的影响

目的通过检测不同浓度石松生物碱对东乡伊蚊Ⅳ龄幼虫体内乙酰胆碱酯酶(AChE)活性的变化,以初步了解石松生物碱对蚊幼虫的杀灭机制。方法采用微板法检测经不同浓度石松生物碱不同时间处理后的东乡伊蚊Ⅳ龄幼虫的AChE活性。结果经浓度为0.625、1.25、2.50、5、10mg/L石松生物碱处理4h内的蚊幼虫体内AChE活性呈增强趋势,于4h左右其吸光度(A)值分别达到最大值0.3714、0.3839、0.3752、0.3750、0.3882,但随着处理时间的延长,其活性转而迅速下降,除0.625mg/L组外,均于6h达到较低点,A值分别为0.3567、0.3176、0.2890、0.3020。此后又逐渐回升。而浓度为20mg/L的石松生物碱2h内即可抑制AChE的活性,并使其活性逐步降低,于6h左右其A值达到最小,为0.3158。此后,随着处理时间的延长,A值又逐渐回升。结论石松生物碱对东乡伊蚊Ⅳ龄幼虫体内AChE有较显著抑制作用,但在应用中需注意使用剂量及时间。

伸筋草总生物碱对类风湿关节炎大鼠脾脏淋巴细胞增殖及IL-17A、TGF-β水平的影响

目的探究伸筋草总生物碱对类风湿关节炎大鼠脾脏淋巴细胞增殖及白细胞介素-17A(IL-17A)、转化生长因子-β(TGF-β)水平的影响。方法取60只雄性SD大鼠,随机选取10只作为正常对照组,余大鼠采用皮下注射弗氏佐剂的方法复制类风湿关节炎模型。将造模成功大鼠随机分为模型组、伸筋草低剂量组、伸筋草高剂量组和甲氨蝶呤组,每组10只。伸筋草低、高剂量组大鼠每日分别灌胃4 mg/kg和8 mg/kg的伸筋草总生物碱,甲氨蝶呤组每日灌胃0.5 mg/kg的甲氨蝶呤溶液,正常对照组和模型组每日灌胃等体积的生理盐水。连续灌胃21 d后,取各组大鼠脾脏,HE染色后光镜下观察脾脏组织病理形态;采用细胞增殖法(体外分离模型组大鼠脾脏中淋巴细胞,设空白组、伴刀豆球蛋白组、伸筋草25μmol/L组和伸筋草12.5μmol/L组)测定大鼠脾脏淋巴细胞增殖情况,采用酶联免疫吸附法测定脾细胞上清液中IL-17A和TGF-β水平。结果与模型组比较,伸筋草高、低剂量组和甲氨蝶呤组大鼠脾脏组织结构轮廓清晰,红髓充血、白髓增生减少,炎性浸润减少。细胞增殖实验显示,伸筋草25μmol/L组和伸筋草12.5μmol/L组脾脏淋巴细胞增殖OD值均明显低于伴刀豆球蛋白组(P均<0.05)。与模型组比较,伸筋草高剂量组和甲氨蝶呤组IL-17A水平均明显降低(P均<0.05),伸筋草高、低剂量组和甲氨蝶呤组TGF-β水平均明显升高(P均<0.05)。结论伸筋草总生物碱可以明显抑制类风湿关节炎大鼠脾脏组织淋巴细胞增殖和炎性细胞浸润,其作用与部分恢复辅助性T细胞17(Th17)/调节性T细胞(Treg)的动态平衡密切相关。