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.     

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.     

A New Alkaloid from Lycopodium japonicum Thunb.

A new alkaloid, miyoshianine C ( 1 ), was isolated from the whole plants of Lycopodium japonicum Thunb. , together with the known four compounds α‐obscurine ( 2 ), lycodoline ( 3 ), miyoshianine A ( 4 ), and lucidioline ( 5 ). Their structures were elucidated on the basis of in‐depth spectroscopic analysis.     

Huperzine V, A New Lycopodium Alkaloid from Huperzia serrata

Huperzine V, a new Lycopodium alkaloid, was isolated from the whole plant of Huperzia serrata, and the absolute stereochemistry was determined by X-ray crystallographic analysis.     

Malycorins A--C, New lycopodium alkaloids from Lycopodium phlegmaria

A novel C(19)N-type Lycopodium alkaloid, malycorin A (1) consisting of a serratinane skeleton with 2-propanol unit has been isolated from the club moss Lycopodium phlegmaria, together with two new C(16)N-type alkaloids, malycorins B (2) and C (3), and the structures and relative stereochemistry were elucidated on the basis of spectroscopic data.     

Isolation of a new lycodine alkaloid from Lycopodium japonicum

A new lycodine alkaloid, N-methylhydroxypropyllycodine (1), was isolated from the club moss Lycopodium japonicum Thunb, together with five known compounds, N-methyllycodine (2), huperzinine (3), β-obscurine (4), α-obscurine (5) and des-N-methyl-α-obscurine (6). Their structures were elucidated by spectroscopic analyses, including 2D NMR techniques.     

Huperzine W,a Novel 14 Carbons Lycopodium Alkaloid from Huperzia serrata

Lycopodium plants have long been studied and many alkaloids have been reported thus far. Most of the compounds reported have a common formula of C16N1. During the course of chemical investigation on Huperzia serrata, we gained huperzine W (1, 25 mg from 10 kg dry whole plant), a novel compound which possessed a unique structure among Lycopodium alkaloids, along with a known compound, alopecuridine (2)2. In present paper, we report on the isolation and structural elucidation of 1. 1 2 H…     

Sieboldine A, a novel tetracyclic alkaloid from Lycopodium sieboldii, inhibiting acetylcholinesterase

[structure: see text] A novel Lycopodium alkaloid with an unprecedented fused-tetracyclic ring system consisting of an aza-cyclononane ring having a N-hydroxy group, a cyclohexanone, a cyclopentanone, and a tetrahydrofuran ring, sieboldine A (1), was isolated from the club moss Lycopodium sieboldii. The structure and relative stereochemistry were elucidated on the basis of 2D NMR data and X-ray analysis. Sieboldine A (1) exhibited a potent inhibitory activity against acetylcholinesterase and modest cytotoxicity.     

Huperzine H, a New Lycopodium Alkaloid from Huperzia serrata

Huper:iaserrata(Thunb.)Trev.isoneofthemostcommonlyusedtraditionalChineseherbalmedicinesforthetreatmentofcontusions,strains,swellingsandschirophremas'etc..Manylycopodiumalkaloidshavebeenisolated2'3fromitincludinghuperzineA,acompoundwhichhasshownpotentialeffectsonAlzheimedisease.Inourinvestigations.threenewlycopodiumalkaloidswereobtainedandreported"'.ThispaperdealswiththeidentificationofhuperzineH--anewlycopodiumalkaloidwithanovelskeleton.HLlperzineHiscolorlessneedleswithIQ].-216(c0.02.CHC…     

Lycopalhine A, a novel sterically congested Lycopodium alkaloid with an unprecedented skeleton from Palhinhaea cernua

A novel sterically congested Lycopodium alkaloid named lycopalhine A (1) that possesses a fused hexacyclic (5/5/5/6/6/6) ring system comprising a 5,9-diaza-tricyclo[6.2.1.0(4,9)]undecane moiety and a tricyclo[5.2.1.0(4,8)]decane moiety was isolated from Palhinhaea cernua L. The structure and absolute configuration were determined by spectroscopic and computational methods.     

Nankakurine A, a novel C16N2-type alkaloid from Lycopodium hamiltonii

[sstructure: see text] A novel, fused-tetracyclic Lycopodium alkaloid, nankakurine A (1), consisting of a cyclohexane ring and a 3-aza-bicyclo[3.3.1]nonane ring connected to a piperidine ring through a spiro carbon, was isolated from the club moss Lycopodium hamiltonii. The structure and relative stereochemistry were elucidated on the basis of spectroscopic data.     

A New Lycopodine-type Alkaloid from Lycopodium japonicum

A new lycopodine-type alkaloid, 12β-hydroxy-acetylfawcettiine N-oxide (1), together with seven known analogues, acetyllycoposerramine M (2), lycopodine (3), lycoclavine (4), diphaladine A (5), lycoposerramine K (6), 11β-hydroxy-12-epilycodoline (7) and fawcettiine (8), were isolated from Lycopodium japonicum. Their structures were established by mass spectrometry and 1D and 2D NMR techniques. The isolated alkaloids were assayed for their inhibition activities against acetylcholinesterase, but no inhibitory activities for the compounds were detected.     

Himeradine A,a novel C27N3-type alkaloid from Lycopodium chinense

A novel C(27)N(3)-type Lycopodium alkaloid consisting of a fastigiatine-type skeleton (C(16)N(2)) and a quinolizidine moiety (C(11)N), himeradine A (1), has been isolated from the club moss Lycopodium chinense, and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data.     

Lycoperine A, A novel C27N3-type pentacyclic alkaloid from Lycopodium hamiltonii, inhibiting acetylcholinesterase

[structure: see text] A novel C(27)N(3)-type pentacyclic Lycopodium alkaloid, lycoperine A (1) consisting of two octahydroquinoline rings and a piperidine ring, was isolated from the club moss Lycopodium hamiltonii. The structure and relative stereochemistry were elucidated on the basis of 2D NMR data and chemical transformation. Lycoperine A (1) exhibited an inhibitory activity against acetylcholinesterase.     

Exploratory studies towards a total synthesis of the unusual bridged tetracyclic Lycopodium alkaloid lycopladine H

A strategy for a total synthesis of the structurally novel Lycopodium alkaloid lycopladine H has been investigated. Key steps that have been tested include: 1. a regioselective Diels-Alder cycloaddition of nitroethylene with an o-quinone ketal to produce the bicyclo[2.2.2]octane moiety of the alkaloid; 2. a stereoselective Henry reaction to generate the requisite functionality and configuration at C-5; 3. a stereoselective catalytic hydrogenation of a trisubstituted alkene to set the C-15 methyl configuration.     

Construction of the azocane (azacyclooctane) moiety of the Lycopodium alkaloid lycopladine H via an intramolecular hydroaminomethylation strategy

An efficient synthetic strategy has been developed for annulation of an azocane ring onto a bicyclo[2.2.2]octane scaffold via an intramolecular hydroaminomethylation protocol to generate an advanced intermediate bearing three of the four rings of the structurally unique Lycopodium alkaloid lycopladine H (1).     

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.     

Optimization of Pressurized Liquid Extraction of Lycopodiaceae Alkaloids Obtained from Two Lycopodium Species

Alkaloids of the Lycopodiaceae family are of great interest to researchers due to their numerous properties and wide applications in medicine. They play a very important role mainly due to their potent antioxidant, antidepressant effects and a reversible ability to inhibit acetylcholinesterase (AChE) enzyme activity. This property is of immense importance due to the growing problem of an increasing number of patients with neurodegenerative diseases in developed countries and a lack of effective and efficient treatment for them. Numerous studies have shown that Lycopodiaceae alkaloids are a rich source of AChE inhibitors. In the obtaining of new therapeutic phytochemicals from plant material, the extraction process and its efficiency is crucial. Therefore, the aim of this work was to optimize the conditions of modern PLE to obtain bioactive alkaloids from two Lycopodium species: L. clavatum L. and L. annotinum L. Five different solvents of different polarity were used for prepared plant extracts in order to compare the alkaloid content in and thereby effectiveness of the entire extraction. PLE parameters were used based on multiple studies conducted that gave the highest alkaloids recovery. Crude extracts were purified using solid-phase extraction (SPE) on Oasis HLB cartridge and examined by HPLC/ESI-QTOF–MS of the highly abundant alkaloids. To the best of our knowledge, this is the first time such high recoveries have been obtained for known Lycopodiaceae alkaloids. The best extraction results of alkaloid-lycopodine were detected in the dichloromethane extract from L. clavatum, where the yield exceeded 45%. The high recovery of annotinine above 40% presented in L. annotinum was noticed in dichloromethane and ethyl acetate extracts. Moreover, chromatograms were obtained with all isolated alkaloids and the best separation and quality of the bands in methanolic extracts. Interestingly, no alkaloid amounts were detected in cyclohexane extracts belonging to the non-polar solvent. These results could be helpful for understanding and optimizing the best conditions for isolating potent AChE inhibitors.     

IMDA/retro-Mannich approach to cis-perhydroquinoline Lycopodium alkaloids: asymmetric synthesis of (+)-luciduline

[formula: see text] The first chiral auxiliary mediated asymmetric synthesis of the naturally occurring Lycopodium alkaloid (+)-luciduline has been accomplished. Key steps include an IMDA reaction of a chiral dihydropyridine, a subsequent retro-Mannich ring opening, and a novel cationic reductive cyclization reaction.     

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.