Lycopodium Alkaloids from Lycopodium obscurum L.

Two new Lycopodium alkaloids, named obscurumines F and G ( 1 and 2 , resp.), together with eleven known alkaloids, were isolated from the club moss Lycopodium obscurum L. Their structures were elucidated on the basis of spectroscopic analyses.     

Lycopladines F and G, new C16N2-type alkaloids with an additional C4N unit from Lycopodium complanatum

Two new Lycopodium alkaloids, lycopladines F (1) and G (2), have been isolated from the club moss Lycopodium complanatum, and the structures and relative stereochemistries of 1 and 2 were elucidated on the basis of spectroscopic data. Lycopladine F (1) is a rare C₁₆N₂-type Lycopodium alkaloid possessing an amino acid residue (C₄N).     

New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C₁₆N₂ type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1-4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7-10.     

Synthesis and reactivity of pelletierine-derived building blocks and pelletierine analogs

Lycopodium alkaloids are unique (and often impressive in terms of structures) polycyclic alkaloids that attract great interest from a biological point of view and that also provide ideal targets for total synthesis. Propylpiperidine units closely related to pelletierine are involved in the biosynthesis of these alkaloids. Therefore, stable pelletierine-like compounds, especially a (R)-phenylglycinol-based oxazolopiperidine analog, were prepared and their reactivity investigated. The compounds described in this work expand the tool-box of small building blocks in the piperidine series and pelletierine analogs and could be suitable for the synthesis of Lycopodium alkaloids following biosynthetically inspired strategies.     

Complanadine B, obscurumines A and B, new alkaloids from two species of Lycopodium

A new dimer of C₁₆N₂ type alkaloid, complanadine B (1), and two new C₁₆N type alkaloids, obscurumines A (2) and B (3), have been isolated from the club moss Lycopodium complanatum and L. obscurum, respectively. The structures and stereochemistry of 1-3 were elucidated by combination of 2D NMR spectra and chemical transformation. Complanadine A (4) isolated together with 1 induced secretion of neurotrophic factors from human astrocytoma cells.     

Two New Lycopodium Alkaloids from Lycopodium obscurum

Two new Lycopodium alkaloids, (+)‐cermizine D N‐oxide ( 1 ) and (8β)‐8‐(acetyloxy)obscurumine A ( 2 ), along with five known compounds, were isolated from the crude alkaloid portion of Lycopodium obscurum. Their structures were elucidated on the basis of spectroscopic data and chemical correlation. All of these alkaloids were tested in an assay for acetylcholine esterase (AChE) inhibitory activity.     

Lannotinidines A-G, new alkaloids from two species of Lycopodium

Seven new Lycopodium alkaloids, lannotinidines A-G (1-7), have been isolated from the club moss Lycopodium annotinum and L. annotinum var. acrifolium. Stereochemistry of 1-7 was elucidated by combination of NOESY correlations and chemical transformation. Lannotinidines B-E (2-5) elevated NGF mRNA expression.     

Two new Lycopodium alkaloids from Phlegmariurus phlegmaria (L.) Holub

Two new Lycopodium alkaloids, 4β-hydroxynankakurine B (1) and Δ^13,N,N_α-methylphlegmarine-N_β-oxide (2), together with three known analogues, lycoposerramine E (3), nankakurine B (4) and lobscurinol (5), were isolated from Phlegmariurus phlegmaria. Their structures were established by mass spectrometry and 1D and 2D NMR techniques.     

Senepodines B-E, new C22N2 alkaloids from Lycopodium chinense

Four new C₂₂N₂Lycopodium alkaloids, senepodines B-E (2-5), consisting of an octahydroquinoline ring and a quinolizidine ring have been isolated together with senepodine A (1) from the club moss Lycopodium chinense. The relative and absolute stereochemistry of 2-5 were determined by combination of NOESY correlations and chemical transformation, while the absolute configuration of 1 was assigned by exciton chirality method.     

Lycopodium Alkaloids from Huperzia serrata

Three new Lycopodium alkaloids, 2‐chlorohuperzine E ( 1 ), huperzines E′ ( 2 ), and F′ ( 3 ), along with two known compounds, huperzines E and F, were isolated from Huperzia serrata (Thunb .) Trev . Their structures were elucidated by spectroscopic methods.     

Lycopladine A, a new C16N alkaloid from Lycopodium complanatum

A new C₁₆N type alkaloid, lycopladine A (1), has been isolated from the club moss Lycopodium complanatum, and the structure and relative stereochemistry of 1 were elucidated on the basis of spectral data.     

Lycogladines A-H,fawcettimine-type Lycopodium alkaloids from Lycopodium complanatum var. glaucum Ching

Five new fawcettimine-type alkaloids (1–5) and three new natural products (6–8), along with four known analogues, fawcettimine (9), fewcettidine (10), lycopoclavamine B (11), and lycopladine B (12), were isolated from the whole plant of Lycopodium complanatum var. glaucum Ching. The structures of lycogladines A-H (1–8) were determined based on HRESIMS, 1D and 2D NMR spectroscopic analysis, as well as single-crystal X-ray diffraction. Compound 1 possesses a new ring system that is formed through the linkage of C-13-OC-2, which is rarely present in Lycopodium alkaloids (LAs). Compounds 1–8 were tested for their β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) inhibitory activities.     

The Lycopodium alkaloids

Lycopodium alkaloids are quinolizine, or pyridine and alpha-pyridone type alkaloids. Some Lycopodium alkaloids are potent inhibitors of acetylcholinesterase (AChE). Huperzine A (HupA) is reported to increase efficiency for learning and memory in animals, and it shows promise in the treatment of Alzheimer's disease (AD). 201 Lycopodium alkaloids from 54 species of Lycopodium (sensu lato) have been reported so far. This review is intended to to cover the chemical, pharmacological and clinical research on Lycopodium alkaloids reported in the literature from the spring of 1993 to August 2004. Structures of 81 new Lycopodium alkaloids are presented, classified and analyzed. The structural characters and biogenetic relationships of the four major Lycopodium alkaloid groups (lycopodine, lycodine, fawcettimine and miscellaneous) are discussed. Bioactivities of Lycopodium alkaloids, especially HupA, are summarized. In particular, the effect of HupA and other cholinesterase inhibitors (anti-AD drugs) on acetylcholine esterase (AChE) activity in the rat cortex and butylcholine esterase activity are compared. Structure-activity relationships and structure modifications of HupA and its analogs are described. Information on clinical trials with HupA and its derivative ZT-1 is presented. The state of HupA availability and recent advances in in vitro propagation of HupA producing plants are outlined. Finally, hypotheses about Lycopodium alkaloid biosynthetic pathways are discussed.     

Lycochinines A-C, novel C27N3 alkaloids from Lycopodiumchinense

Three novel C₂₇N₃-type Lycopodium alkaloids, lycochinines A-C (1-3) consisting of an octahydroquinoline or a decahydroquinoline, a quinolizidine, and a piperidine, were isolated from the club moss Lycopodium chinense. The relative stereochemistry of 1-3 was determined by a combination of NOESY correlations and chemical transformations.     

Antifungal Activity of New Diterpenoid Alkaloids Isolated by Different Chromatographic Methods from Delphinium peregrinum L. var. eriocarpum Boiss

This paper aimed to investigate the potential antifungal influences of new alkaloids from Delphinium peregrinum L. var. eriocarpum Boiss. New Diterpenoid alkaloids Delcarpum (1), Hydrodavisine (4) and known alkaloids Peregrine (2), Delphitisine (3) were isolated by different chromatographic methods from the aerial parts of D. Peregrinum eriocarpum Boiss, which grows in Syria. The structures of alkaloids were proposed based on 1D NMR spectroscopy ¹H-NMR, ¹³C-NMR, DEPT-135, DEPT-90, 2D NMR spectroscopy DQF-COSY, HMQC, EI-Ms mass spectrum, and IR spectroscopic measurements. The antifungal activity of the isolated alkaloids was evaluated against different dermatophyte fungal isolates compared with fluconazole. In the case of Peregrine (2) the minimum inhibitory concentrations(MICs) recorded 128–256, 32–64, and 32 for Epidermophyton floccosum, Microsporum canis, and Trichophyton rubrum, respectively, compared to 32–64, 16, and 32 μg/mL in the case of fluconazole, respectively. The MICs recorded on application of the four alkaloids mixture were 64, 32, and 16 in the case of E. floccosum, M. canis, and T. rubrum, respectively, which were significantly lower than that measured for each of the individual alkaloid and were compatible for fluconazole. In conclusion, MICs of the tested alkaloids showed a variable potential effect on the investigated fungal isolates. Peregrine (2) was the most effective alkaloid, however, the application of the mixture of alkaloids induced significant synergistic activity that was more pronounced than the application of individual ones.     

Alcaloïdes indoliques—CII : Deux nouveaux types d'alcaloïdes indoliques l'ibophyllidine,dérivé du nor-21(+)pandolane et l'iboxyphylline dérivé de l'abeo-21(20→19) (+)pandolane,retirés des feuilles de tabernanthe iboga baillon et de t. subsessilis stapf

Two alkaloids from Iboga, ibophyllidine and iboxyphylline, were isolated from the leaves of T. iboga and T. subsessilis. Chemical and physical data led to their structural assignments. The structure of iboxyphylline was confirmed by X-ray analysis. These alkaloids belong to a new Iboga sub-group.     

Alcaloides du peripterygia marginata (baill.) lues. (célastracées)—I : Révision de la structure de la périphylline

Six new alkaloids, periphylline 1, isoperiphylline 5, dihydroperiphylline 21, neoperiphylline 22, perimargine 23 and dihydroperimargine 24 have been isolated from the leaves of Peripterygia marginata. All these alkaloids contain a thirteen-membered ring system derived from dicinnamoylspermidine.     

New oxindole and indole alkaloids from Gelsemium rankinii

Six new humantenine-type (1-6) and two new gelsemine-type (7, 8) oxindole alkaloids and one new indole alkaloid (9) were isolated from the leaves and branches of Gelsemium rankinii. The structures of the new alkaloids were determined by spectroscopic analyses. Among them, 6-hydroxyhumantenine (5) is the first example of a Gelsemium alkaloid with an oxygen function at C-6 position, and is a plausible biogenetic precursor of gelsemine-type alkaloids.     

Leucomidines A–C,novel alkaloids from Leuconotis griffithii

Two novel indole alkaloids and new quinazoline alkaloids, namely leucomidines A–C (1–3), were isolated from the barks of Leuconotis griffithii. The structures including the absolute configuration were elucidated on the basis of spectroscopic data, chemical means, and CD calculations. The quinazoline alkaloid, 3, is proposed to be derived from the same biogenetic precursor as the indole alkaloids 1 and 2.     

Lycodine‐Type Alkaloids from Lycopodium casuarinoides

Two new lycodine‐type alkaloids, huperzinine N‐oxide ( 1 ) and 8,15‐dihydrohuperzinine ( 2 ) as well as five known compounds, huperzinine ( 3 ), huperzine B ( 4 ), huperzine D ( 5 ), N‐demethylhuperzinine ( 6 ), and β‐obscurine ( 7 ), were isolated from the club moss Lycopodium casuarinoides. The structures of 1 and 2 were elucidated by spectroscopic methods and chemical transformation. The absolute configuration of 1 was established by chemical correlation with 3 , and that of 2 was determined by its CD spectrum.