Lycopodium alkaloids--synthetic highlights and recent developments.

Recent progress in the isolation and synthesis of Lycopodium alkaloids is reviewed. A general discussion of the importance of Lycopodium alkaloids and a brief outline of their biosynthesis is followed by a comprehensive tabular overview of all alkaloids isolated since the last major review in this area in 2005. This section is followed by a discussion of highlights and milestone achievements in the synthesis of Lycopodium alkaloids. The main section of the article is devoted to recent syntheses of Lycopodium alkaloids. Previous synthetic contributions are briefly outlined to allow a direct comparison of different strategies for the preparation of these important natural products. The literature is covered between 2005 and early 2012.

[1]  F. Toste,et al.  Total synthesis of (+)-fawcettimine. , 2007, Angewandte Chemie.

[2]  D. Gang,et al.  The Lycopodium alkaloids. , 2004, Natural product reports.

[3]  H. Takayama,et al.  Asymmetric total syntheses of cyclic nitrone-containing phlegmarine-type Lycopodium alkaloids, lycoposerramines-X and -Z. , 2009, The Journal of organic chemistry.

[4]  M. Jung,et al.  Enantiospecific formal total synthesis of (+)-fawcettimine. , 2010, Organic letters.

[5]  H. Lee,et al.  Synthesis of huperzine B through ring closing metathesis , 2004 .

[6]  Da-yuan Zhu,et al.  Two new N-oxide Lycopodium alkaloids from Huperzia serrata , 2009, Natural Product Research.

[7]  H. Morita,et al.  Nankakurine A, a novel C16N2-type alkaloid from Lycopodium hamiltonii. , 2004, Organic letters.

[8]  R. Gupta,et al.  Biosynthesis of lycopodine from lysine and acetate. The pelletierine hypothesis , 1970 .

[9]  P. Albersheim,et al.  Occurrence of the Primary Cell Wall Polysaccharide Rhamnogalacturonan II in Pteridophytes, Lycophytes, and Bryophytes. Implications for the Evolution of Vascular Plants1 , 2004, Plant Physiology.

[10]  R. H. Burnell,et al.  LYCOPODIUM ALKALOIDS: PART IV. ALKALOIDS OF JAMAICAN LYCOPODIUM CLAVATUM LINN. , 1961 .

[11]  C. Liao,et al.  Concise and efficient total synthesis of Lycopodium alkaloid magellanine. , 2002, Angewandte Chemie.

[12]  C. Chassaing,et al.  Asymmetric palladium annulation: formal synthesis of (+)-huperzine A , 1999 .

[13]  M. Wolff Cyclization of N-Halogenated Amines (The Hofmann-Löffler Reaction). , 1963 .

[14]  Amos B. Smith,et al.  Total syntheses of (+)-lyconadin A and (-)-lyconadin B. , 2007, Journal of the American Chemical Society.

[15]  Davidr . Evans,et al.  Polycyclic molecules from linear precursors: stereoselective synthesis of clavolonine and related complex structures. , 2005, Angewandte Chemie.

[16]  L. Qian,et al.  A total synthesis of (±)-huperzine A , 1989 .

[17]  H. Takayama,et al.  Syntheses of Fawcettimine-Type Lycopodium Alkaloids Utilizing the Pauson-Khand Reaction , 2012 .

[18]  J. Cha,et al.  Total Synthesis of Clavepictines A and B. Cross-Coupling of an Acylenamino Triflate and Cyclization of a δ-Aminoallene , 1997 .

[19]  H. Morita,et al.  Lyconadin A, a novel alkaloid from Lycopodium complanatum. , 2001, The Journal of organic chemistry.

[20]  W. Ayer,et al.  The alkaloids of Lycopodium cernuum L. III. The synthesis of dihydrodeoxyepiallocernuine , 1967 .

[21]  T. Hemscheidt,et al.  Biosynthesis of lycopodine: incorporation of acetate via an intermediate with C2v symmetry , 1993 .

[22]  L. Mander,et al.  Regioselective synthesis of β-ketoesters from lithium enolates and methyl cyanoformate , 1984 .

[23]  C. Bolm,et al.  General synthesis of unsymmetrical norbornane scaffolds as inducers for hydrogen bond interactions in peptides. , 2004, The Journal of organic chemistry.

[24]  D. Barton,et al.  A New Photochemical Reaction1 , 1960 .

[25]  Karl M. Smith,et al.  Total synthesis of (.+-.)-fawcettimine , 1989 .

[26]  C. Heathcock,et al.  Total synthesis of (±)-Lycodine , 1979 .

[27]  B. B. Liau,et al.  Total synthesis of (+)-fastigiatine. , 2010, Journal of the American Chemical Society.

[28]  R. Oda,et al.  Entstehung von P-Ylid aus Triphenylphosphin und Acrylsäurederivaten , 1964 .

[29]  H. Morita,et al.  Lycoperine A, A novel C27N3-type pentacyclic alkaloid from Lycopodium hamiltonii, inhibiting acetylcholinesterase. , 2006, Organic letters.

[30]  J. Kozak,et al.  Total synthesis of (+)-fawcettidine. , 2008, Angewandte Chemie.

[31]  T. Harayama,et al.  Total synthesis of the lycopodium alkaloid (±)-serratinine , 1974 .

[32]  W. Ayer,et al.  THE STRUCTURE OF LYCODINE , 1960 .

[33]  W. Oppolzer,et al.  A total synthesis of d,l-luciduline by a regioselective intramolecular addition of an N-alkenylnitrone , 1976 .

[34]  J. Tsuji,et al.  Preparation and rearrangement of 2-allyloxyethyl aryl sulfoxides; a mercury-free claisen sequence , 1990 .

[35]  Y. Obara,et al.  Lycovatine A, a C16N-Type Quaternary Alkaloid from Lycopodium clavatum var. robustum , 2006 .

[36]  D. MacMillan,et al.  Modern strategies in organic catalysis: The advent and development of iminium activation , 2006 .

[37]  Giuseppe Campiani,et al.  A palladium-catalyzed route to huperzine A and its analogues and their anticholinesterase activity , 1993 .

[38]  S. P. Waters,et al.  Concise total syntheses of the Lycopodium alkaloids (+/-)-nankakurines A and B via luciduline. , 2010, Organic letters.

[39]  R. Grubbs,et al.  Tandem catalysis: the sequential mediation of olefin metathesis, hydrogenation, and hydrogen transfer with single-component Ru complexes. , 2001, Journal of the American Chemical Society.

[40]  H. Morita,et al.  Lycotetrastine A, a novel hexacyclic alkaloid from Huperzia tetrasticha , 2011 .

[41]  J. Stryker,et al.  Hydride-mediated homogeneous catalysis. Catalytic reduction of .alpha.,.beta.-unsaturated ketones using [(Ph3P)CuH]6 and H2 , 1989 .

[42]  Yong-tang Zheng,et al.  Lycojapodine A, a novel alkaloid from Lycopodium japonicum. , 2009, Organic letters.

[43]  A. Kozikowski,et al.  A practical synthesis of the Chinese "nootropic" agent huperzine A: a possible lead in the treatment of Alzheimer's disease , 1989 .

[44]  R. W. Hoffmann,et al.  Allylic 1,3-strain as a controlling factor in stereoselective transformations , 1989 .

[45]  F. Matsuda Hydroxyl-Directed Carbon-Carbon Bond Formation Reactions Mediated by Samarium (II) Iodide , 1995 .

[46]  H. Dugas,et al.  Synthesis in the series of lycopodium alkaloids. VII. The synthesis of 12-epi-lycopodine. , 1967, Tetrahedron letters.

[47]  Y. Liu,et al.  Two New Lycopodine Alkaloids from Huperzia serrata , 2010 .

[48]  Yujin. Huang,et al.  Palladium catalyzed annulation reaction using a bifunctional allylic alkylating agent , 1988 .

[49]  T. Doi,et al.  Facile synthesis of asymmetric quaternary centers based on diastereoselective protection of the carbonyl group at the symmetrical position , 2010 .

[50]  Kan’ichiro Ishiuchi,et al.  Lycopladine A, a new C16N alkaloid from Lycopodium complanatum , 2006 .

[51]  J. Palmer,et al.  Multigene phylogeny of land plants with special reference to bryophytes and the earliest land plants. , 2000, Molecular biology and evolution.

[52]  Kan’ichiro Ishiuchi,et al.  Lycopladines F and G, new C16N2-type alkaloids with an additional C4N unit from Lycopodium complanatum , 2009 .

[53]  A. Padwa,et al.  Utilization of the Intramolecular Cycloaddition-Cationic pi-Cyclization of an Isomünchnone Derivative for the Synthesis of (+/-)-Lycopodine. , 1997, The Journal of organic chemistry.

[54]  Xingxing Wu,et al.  Total synthesis of (-)-8-deoxyserratinine via an efficient Helquist annulation and double N-alkylation reaction. , 2010, Organic letters.

[55]  R. Gupta,et al.  Biosynthesis of lycopodine. Incorporation of Δ1-piperideine and of pelletierine , 1970 .

[56]  H. Nozaki,et al.  Novel template effects of distannoxane catalysts in highly efficient transesterification and esterification , 1991 .

[57]  Liming Zhang,et al.  A two-step, formal [4 + 2] approach toward piperidin-4-ones via Au catalysis. , 2009, Journal of the American Chemical Society.

[58]  H. Morita,et al.  Complanadine F, a novel dimeric alkaloid from Lycopodium complanatum , 2000, Journal of natural medicines.

[59]  H. Morita,et al.  Lycoparins A-C, new alkaloids from Lycopodium casuarinoides inhibiting acetylcholinesterase. , 2008, Bioorganic & medicinal chemistry.

[60]  S. Condon,et al.  Synthetic applications of gilman reagents derived from 2-bromo-2-cycloalken-1-one Ethylene Ketals , 1991 .

[61]  W. Ayer,et al.  The alkaloids of Lycopodium cernuum L. II. The stereochemistry of cernuine and lycocernuine , 1967 .

[62]  Jin Sung Kim,et al.  Stereocomplementary Construction of Optically Active Bicyclo[4.3.0]nonenone Derivatives. , 1999, The Journal of organic chemistry.

[63]  Kan’ichiro Ishiuchi,et al.  Lycopladine H, a novel alkaloid with fused-tetracyclic skeleton from Lycopodium complanatum , 2009 .

[64]  X. Tang,et al.  [Effects of huperzine A and B on skeletal muscle and the electroencephalogram]. , 1987, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[65]  R. Manske,et al.  The alkaloids of Lycopodium species; Lycopodium lucidulum Michx. (Urostachys lucidulus Herter). , 1946, Canadian journal of research.

[66]  J. Inanaga,et al.  SmI2-induced reductive cross-coupling of carbonyl compounds with (α,β-unsaturated esters , 1986 .

[67]  M. Sugiura,et al.  Enantioselective transfer aminoallylation: synthesis of optically active homoallylic primary amines. , 2006, Journal of the American Chemical Society.

[68]  L. Overman,et al.  Total synthesis of (+)-nankakurines A and B and (±)-5-epi-nankakurine A. , 2010, The Journal of organic chemistry.

[69]  R. Al-awar,et al.  IMDA/retro-Mannich approach to cis-perhydroquinoline Lycopodium alkaloids: asymmetric synthesis of (+)-luciduline. , 1999, Organic letters.

[70]  Z. Horii,et al.  Total synthesis of (±)-anhydrolycodoline and (±)-lycopodine , 1978 .

[71]  J. Inanaga,et al.  SmI2-Induced highly regioselective reduction of α,β-epoxy esters and γ,δ-epoxy-α,β-unsaturated esters. An efficient route to optically active β-hydroxy and δ-hydroxy esters , 1987 .

[72]  Y. Obara,et al.  Lycopladine E, a new C16N1-type alkaloid from Lycopodium complanatum , 2007 .

[73]  Yongcheng Song,et al.  A concise asymmetric synthesis of 5,8-disubstituted indolizidine alkaloids. Total synthesis of ()-indolizidine 209B , 2002 .

[74]  D. Bai,et al.  The First Total Synthesis of (±)-Huperzine B , 1997 .

[75]  J. Inanaga,et al.  A direct synthesis of γ-, δ-, and ε-lactones utilizing SmI2-induced Barbier-type reaction in the presence of hexamethylphosphoric triamide (HMPA) , 1987 .

[76]  R. Manske,et al.  The alkaloids of Lycopodium species; Lycopodium annotinum var. acrifolium, Fern. and the structure of annotinine. , 1947, Journal of the American Chemical Society.

[77]  D. Zhu,et al.  Three Lycopodium Alkaloid N-Oxides from Huperzia serrata , 2000, Planta medica.

[78]  H. Takayama,et al.  Asymmetric total synthesis of a pentacyclic Lycopodium alkaloid: huperzine-Q. , 2011, Angewandte Chemie.

[79]  C. Poon,et al.  A new one-flask Ramberg–Bäcklund reaction , 1994 .

[80]  T. Honda Development of Samarium Diiodide-Promoted Reductive Carbon—Nitrogen Bond Cleavage Reaction of α-Amino Carbonyl Compounds: Application to the Synthesis of Biologically Active Alkaloids , 2011 .

[81]  D. Evans,et al.  The total synthesis of ( )-luciduline. , 1972, Journal of the American Chemical Society.

[82]  D. Grotjahn,et al.  A general bifunctional catalyst for the anti-Markovnikov hydration of terminal alkynes to aldehydes gives enzyme-like rate and selectivity enhancements. , 2004, Journal of the American Chemical Society.

[83]  F. Inagaki,et al.  Total syntheses of (+)-fawcettimine and (+)-lycoposerramine-B. , 2010, The Journal of organic chemistry.

[84]  A. F. Heyduk,et al.  Isolation and characterization of a neutral imino-semiquinone radical. , 2008, Journal of the American Chemical Society.

[85]  D. Taber,et al.  Conjugate addition of lithiated methyl pyridines to enones. , 2010, The Journal of organic chemistry.

[86]  W. Ayer,et al.  LYCOPODIUM ALKALOIDS: VII. LYCODOLINE (ALKALOID L.8) , 1964 .

[87]  Y. Obara,et al.  Lannotinidines A–G, new alkaloids from two species of Lycopodium , 2005 .

[88]  E. Prabhakaran,et al.  Free Radical-Mediated Vinyl Amination: Access to N,N-Dialkyl Enamines and Their β-Stannyl and β-Thio Derivatives , 2002 .

[89]  R. Sarpong,et al.  Total synthesis of alkaloid (+/-)-G. B. 13 using a Rh(I)-catalyzed ketone hydroarylation and late-stage pyridine reduction. , 2009, Journal of the American Chemical Society.

[90]  K. A. Parker,et al.  Asymmetric catalysis route to anti,anti stereotriads, illustrated by applications. , 2008, Organic letters.

[91]  V. Musil,et al.  Syntheses in the series of Lycopodium alkaloids. IX. Two simple stereospecific syntheses of 12-epi-lycopodine. , 1968, Tetrahedron letters.

[92]  W. Ayer,et al.  Luciduline: a unique type of Lycopodium alkaloid , 1968 .

[93]  P. Potier,et al.  Modification de la reaction de polonovsky , 1967 .

[94]  B. P. Doctor,et al.  Synthesis of a hybrid analog of the acetylcholinesterase inhibitors huperzine A and huperzine B , 2001 .

[95]  C. Sha,et al.  Tandem Radical Cyclizations Initiated with α-Carbonyl Radicals: First Total Synthesis of (+)-Paniculatine , 1999 .

[96]  R. Fournier,et al.  Enantiospecific synthesis of RPR 107880: A new non peptide substance P antagonist , 1996 .

[97]  G. Stork,et al.  The stereospecific total synthesis of dl-lycopodine. , 1968, Journal of the American Chemical Society.

[98]  Fei Liu,et al.  Preparation of enantiopure substituted piperidines containing 2-alkene or 2-alkyne chains: application to total syntheses of natural quinolizidine-alkaloids. , 2010, The Journal of organic chemistry.

[99]  Gang Xu,et al.  Diphaladine A, a New Lycopodium Alkaloid from Diphasiastrum complanatum (Lycopodiaceae): Diphaladine A, a New Lycopodium Alkaloid from Diphasiastrum complanatum (Lycopodiaceae) , 2010 .

[100]  Jae Nyoung Kim,et al.  Synthesis of 1,5-dicarbonyl and related compounds from Baylis–Hillman adducts via Pd-mediated decarboxylative protonation protocol , 2008 .

[101]  R. Sarpong,et al.  Total synthesis of (+)-complanadine A using an iridium-catalyzed pyridine C-H functionalization. , 2010, Journal of the American Chemical Society.

[102]  Raja R. Narayan,et al.  Total synthesis of (+)-lyconadin A and related compounds via oxidative C-N bond formation. , 2009, Journal of the American Chemical Society.

[103]  I. Singh,et al.  Paniculatine. A New Alkaloid from L. paniculatum Desvaux , 1975 .

[104]  S. Martin,et al.  Concise total synthesis of (+/-)-lycopladine A. , 2010, Organic letters.

[105]  H. Morita,et al.  Malycorins A--C, New lycopodium alkaloids from Lycopodium phlegmaria. , 2008, Chemical & pharmaceutical bulletin.

[106]  H. Takayama,et al.  A New Lycopodium Alkaloid, Lycoposerramine‐R, with a Novel Skeleton and Three New Fawcettimine‐Related Alkaloids from Lycopodium serratum , 2009 .

[107]  D. G. Lewis,et al.  THE ALKALOIDS OF LYCOPODIUM SPECIES: XII. RELATIONSHIP BETWEEN SOME OF THE MINOR ALKALOIDS AND LYCOPODINE , 1953 .

[108]  B. Snider,et al.  Synthesis of (±)-7-hydroxylycopodine. , 2012, The Journal of organic chemistry.

[109]  Y. Kita,et al.  Asymmetric total synthesis of clavolonine. , 2011, Organic letters.

[110]  A. Fürstner,et al.  A catalytic approach to (R)-(+)-muscopyridine with integrated "self-clearance". , 2003, Angewandte Chemie.

[111]  H. Takayama,et al.  A new type of lycopodium alkaloid, lycoposerramine-A, from Lycopodium serratum Thunb. , 2001, Organic letters.

[112]  I. Singh,et al.  The alkaloids of L. magellanicum and the structure of magellanine , 1976 .

[113]  J. Richards,et al.  The stereochemistry of the enzymic decarboxylation of L-arginine and of L-ornithine , 1982 .

[114]  Kan’ichiro Ishiuchi,et al.  Lannotinidines H-J, new Lycopodium alkaloids from Lycopodium annotinum. , 2009, Chemical & pharmaceutical bulletin.

[115]  H. Bestmann,et al.  An Improved One-pot Procedure for the Synthesis of Alkynes from Aldehydes , 1996 .

[116]  T. Doi,et al.  Total synthesis of optically active lycopladine A by utilizing diastereoselective protection of carbonyl group in a 1,3-cyclohexanedione derivative. , 2011, The Journal of organic chemistry.

[117]  W. Ayer,et al.  LYCOPODIUM ALKALOIDS: V. THE BROMINATION OF LYCOPODINE AND THE STRUCTURE OF ALKALOID L.20 , 1963 .

[118]  E. S. Binkley,et al.  Total synthesis of lycopodium alkaloids: (.+-.)-lycopodine, (.+-.)-lycodine, and (.+-.)-lycodoline , 1982 .

[119]  H. Morita,et al.  The Lycopodium alkaloids. , 2007, The Alkaloids. Chemistry and biology.

[120]  X. Tang,et al.  [Effects of huperzine A on learning and the retrieval process of discrimination performance in rats]. , 1986, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[121]  Kan’ichiro Ishiuchi,et al.  Lyconadins C and F, new Lycopodium alkaloids from Lycopodium complanatum , 2011 .

[122]  H. Hara,et al.  A formal total synthesis of Lycopodium alkaloid, (±)-magellanine, by using the intramolecular Pauson Khand reaction , 2005 .

[123]  J. Hwu,et al.  Chlorotrimethylsilane, hexamethyldisilane, and 1,2-dimethyl-1,1,2,2-tetraphenyldisilane as oxidizing agents in the conversion of hydrazines to 2-tetrazenes. Trimethylsilyl anion as a leaving group , 1989 .

[124]  Stephen M. Canham,et al.  Total synthesis of (+)-sieboldine A. , 2010, Journal of the American Chemical Society.

[125]  W. Ayer,et al.  The synthesis of dl-lycopodine. , 1968, Journal of the American Chemical Society.

[126]  A. Charette,et al.  Asymmetric total synthesis of (+)-luciduline: toward a general approach to related Lycopodium alkaloids. , 2011, The Journal of organic chemistry.

[127]  Y. Obara,et al.  Lycopladines B-D and lyconadin B, new alkaloids from Lycopodium complanatum. , 2006, Bioorganic & medicinal chemistry.

[128]  H. Takayama,et al.  First asymmetric total syntheses of cernuane-type Lycopodium alkaloids, cernuine, and cermizine D. , 2008, Organic letters.

[129]  S. Ohira Methanolysis of Dimethyl (1-Diazo-2-oxopropyl) Phosphonate: Generation of Dimethyl (Diazomethyl) Phosphonate and Reaction with Carbonyl Compounds , 1989 .

[130]  J. Muszyński Alkaloide der europäischen Lykopodiumarten , 1935 .

[131]  T. Fukuyama,et al.  Total Synthesis of Lycoposerramine-R , 2012, Synlett : Accounts and Rapid Communications in Synthetic Organic Chemistry.

[132]  Jia-sen Liu,et al.  The structures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity , 1986 .

[133]  C. Heathcock,et al.  Preparation and reactions of .beta.-chloro-.alpha.,.beta.-unsaturated ketones , 1976 .

[134]  I. Singh,et al.  The alkaloids of L. paniculatum and the structure of paniculatine , 1976 .

[135]  J. Cha,et al.  Diels-Alder Reactions of 2-(N-Acylamino)-1,3-dienes. Atypical Regioselectivity and Endo/Exo Selectivity , 1998 .

[136]  E. Pinard,et al.  Total Synthesis of the Lycopodium Alkaloids Magellanine and Magellaninone by Three-fold Annulation of 2-Cyclopentenone , 1994 .

[137]  R. Manske,et al.  THE ALKALOIDS OF LYCOPODIUM SPECIES: III. LYCOPODIUM ANNOTINUM L. , 1943 .

[138]  H. Tokuyama,et al.  Total synthesis of (-)-strychnine. , 2004, Journal of the American Chemical Society.

[139]  H. Müller,et al.  Eine weitere Synthese von (±)‐Lycopodin , 1982 .

[140]  T. Hemscheidt Tropane and Related Alkaloids , 2000 .

[141]  D. Ramachary,et al.  Organocatalytic sequential one-pot double cascade asymmetric synthesis of Wieland-Miescher ketone analogues from a Knoevenagel/hydrogenation/Robinson annulation sequence: scope and applications of organocatalytic biomimetic reductions. , 2007, The Journal of organic chemistry.

[142]  M. Hirama,et al.  Concise Total Synthesis of (±)‐Lycodine , 2010 .

[143]  Robert M. Williams,et al.  Unified total syntheses of fawcettimine class alkaloids: fawcettimine, fawcettidine, lycoflexine, and lycoposerramine B. , 2012, The Journal of organic chemistry.

[144]  H. Morita,et al.  Carinatumins A-C, new alkaloids from Lycopodium carinatum inhibiting acetylcholinesterase. , 2007, Bioorganic & medicinal chemistry.

[145]  F. Inagaki,et al.  Thermal [2+2] cycloaddition of allenynes: easy construction of bicyclo[6.2.0]deca-1,8-dienes, bicyclo[5.2.0]nona-1,7-dienes, and bicyclo[4.2.0]octa-1,6-dienes. , 2007, The Journal of organic chemistry.

[146]  C. Price,et al.  d- and l-Polyconidine , 1960 .

[147]  G. Stork Progress in the synthesis of polycyclic natural products: The total synthesis of lycopodine , 1968 .

[148]  T. Harayama,et al.  Stereoselective syntheses of lycopodium alkaloids, (±)-fawcettimine and (±)-8-deoxyserratinine , 1979 .

[149]  C. Bolm,et al.  Practical and highly enantioselective ring opening of cyclic meso-anhydrides mediated by cinchona alkaloids. , 2000, The Journal of organic chemistry.

[150]  T. Katoh,et al.  AN ENANTIOSELECTIVE SYNTHESIS OF NATURAL (-)-HUPERZINE A VIA CINCHONA ALKALOIDS-PROMOTED ASYMMETRIC MICHAEL REACTIONS , 1997 .

[151]  T. Fukuyama,et al.  A practical synthesis of (−)-oseltamivir , 2009 .

[152]  C. Chassaing,et al.  A Formal Synthesis of (+)-Huperzine A , 2000 .

[153]  Da-yuan Zhu,et al.  Lycopodine‐Type Lycopodium Alkaloids from Huperzia serrata , 2004 .

[154]  R. Sarpong,et al.  Unified strategy for the synthesis of the "miscellaneous" lycopodium alkaloids: total synthesis of (+/-)-lyconadin A. , 2008, Journal of the American Chemical Society.

[155]  L. Overman,et al.  First total synthesis of Lycopodium alkaloids of the magellanane group. Enantioselective total syntheses of (-)-magellanine and (+)-magellaninone , 1993 .

[156]  R. Sarpong,et al.  Methoxypyridines in the synthesis of Lycopodium alkaloids: total synthesis of (+/-)-lycoposerramine R. , 2010, Organic letters.

[157]  Hua Yang,et al.  Development of an enantioselective route toward the Lycopodium alkaloids: total synthesis of lycopodine. , 2010, The Journal of organic chemistry.

[158]  S. Buchwald,et al.  Catalysts for Suzuki-Miyaura coupling processes: scope and studies of the effect of ligand structure. , 2005, Journal of the American Chemical Society.

[159]  L. Zakharov,et al.  Enantioselective total synthesis of lycopodine. , 2008, Journal of the American Chemical Society.

[160]  H. Takayama,et al.  Asymmetric total syntheses of two phlegmarine-type alkaloids, lycoposerramines-V and -W, newly isolated from Lycopodium serratum. , 2007, Organic letters.

[161]  W. Ayer,et al.  The alkaloids of Lycopodium cernuum L. I. The structures of cernuine and lycocernuine , 1967 .

[162]  E. S. Binkley,et al.  A highly efficient total synthesis of (.+-.)-lycopodine , 1978 .

[163]  J. Mann,et al.  A concise and convergent (formal) total synthesis of huperzine A. , 2007, Organic & biomolecular chemistry.

[164]  D. Schumann,et al.  Synthese des Lycopodium-Alkaloids rac-Lucidulin aus Hexahydro-7-methylchinolin , 1984 .

[165]  N. Miyaura,et al.  Mild iridium-catalyzed borylation of arenes. High turnover numbers, room temperature reactions, and isolation of a potential intermediate. , 2002, Journal of the American Chemical Society.

[166]  H. Hailes,et al.  Synthesis of methyl epijasmonate and cis-3-(2-oxopropyl)-2-(pent-2Z-enyl)-cyclopentan-1-one , 2001 .

[167]  F. Toste,et al.  Gold(I)-catalyzed cyclizations of silyl enol ethers: application to the synthesis of (+)-lycopladine A. , 2006, Angewandte Chemie.

[168]  Y. Obara,et al.  Lyconadins D and E, and complanadine E, new Lycopodium alkaloids from Lycopodium complanatum. , 2011, Bioorganic & medicinal chemistry.

[169]  L. Overman,et al.  Enantioselective total syntheses of nankakurines A and B: confirmation of structure and establishment of absolute configuration. , 2008, Journal of the American Chemical Society.

[170]  B. Snider,et al.  Total synthesis of (-)-senepodine G and (-)-cermizine C. , 2007, The Journal of organic chemistry.

[171]  B. Breit,et al.  Total synthesis of (+)-clavolonine, (-)-deacetylfawcettiine, and (+)-acetylfawcettiine. , 2010, Angewandte Chemie.

[172]  T. Harayama,et al.  Structure of Serratinidine and Fawcettidine. A New Type of Lycopodium Alkaloid , 1970 .

[173]  L. Mander,et al.  C-Acylation of Enolates by Methyl Cyanoformate: An Examination of Site- and Stereoselectivity , 1990 .

[174]  L. Overman,et al.  Strategic use of pinacol-terminated Prins cyclizations in target-oriented total synthesis. , 2003, The Journal of organic chemistry.

[175]  C. Mukai,et al.  Stereoselective total syntheses of three Lycopodium alkaloids, (-)-magellanine, (+)-magellaninone, and (+)-paniculatine, based on two Pauson-Khand reactions. , 2007, The Journal of organic chemistry.

[176]  N. Wikström,et al.  Evolution of Lycopodiaceae (Lycopsida): estimating divergence times from rbcL gene sequences by use of nonparametric rate smoothing. , 2001, Molecular phylogenetics and evolution.

[177]  Y. Obara,et al.  Nankakurine B, A new alkaloid from Lycopodium hamiltonii and revised stereostructure of nankakurine A , 2006 .

[178]  M. Yamaguchi,et al.  The Intra- and Intermolecular Pauson-Khand Reaction Promoted by Alkyl Methyl Sulfides , 1999 .

[179]  E. Pinard,et al.  Total synthesis of the tetracyclic diquinane Lycopodium alkaloids magellanine and magellaninone , 1993 .

[180]  H. Morita,et al.  Cryptadines A and B, novel C27N3-type pentacyclic alkaloids from Lycopodium cryptomerinum. , 2007, Bioorganic & medicinal chemistry.

[181]  T. Fukuyama,et al.  Concise total synthesis of (+)-lyconadin A. , 2011, Journal of the American Chemical Society.

[182]  H. Morita,et al.  Lycochinines A–C, novel C27N3 alkaloids from Lycopodium chinense , 2009 .

[183]  R. Manske,et al.  The alkaloids of Lycopodium species; Lycopodium cernuum L. , 1948, Canadian journal of research.

[184]  F. Anet,et al.  LYCODINE, A NEW ALKALOID OF LYCOPODIUM ANNOTINUM , 1958 .

[185]  T. Harayama,et al.  Total Syntheses of the Lycopodium Alkaloids (±)-Fawcettimine and (±)-8-Deoxyserratinine , 1980 .

[186]  Hee-Seung Lee,et al.  Enantiomerically pure synthesis of β-substituted γ- butyrolactones: A key intermediate to concise synthesis of pregabalin , 2007 .

[187]  G. Sang,et al.  [Drug evaluation of huperzine A in the treatment of senile memory disorders]. , 1991, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[188]  C. Sha,et al.  Intermolecular radical addition reactions of alpha-iodo cycloalkenones and a synthetic study of the formal synthesis of enantiopure fawcettimine. , 2008, Chemical communications.

[189]  Y. Kita,et al.  Concise asymmetric synthesis of a model compound, (4S,5S,6S)-6-(2,2-dimethoxy)ethyl-4,5-epoxy-6-hydroxy-2-cyclohexenone, for the cyclohexenone core of scyphostatin , 2002 .

[190]  J. Mulzer,et al.  Synthesis of the lycopodium alkaloid (+)-lycoflexine. , 2010, Journal of the American Chemical Society.

[191]  W. Ayer The lycopodium alkaloids. , 1991, Natural product reports.

[192]  H. Takayama,et al.  First asymmetric total syntheses of fawcettimine-type Lycopodium alkaloids, lycoposerramine-C and phlegmariurine-A. , 2009, Organic letters.

[193]  D. Maclean,et al.  The total synthesis of (±)-luciduline , 1979 .

[194]  D. MacMillan,et al.  New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Diels−Alder Reaction , 2000 .

[195]  Da-yuan Zhu,et al.  Two New Nitrone Alkaloids from Huperzia serrata , 2008 .

[196]  T. Hemscheidt,et al.  A CLASSICAL PARADIGM OF ALKALOID BIOGENESIS REVISITED : ACETONEDICARBOXYLIC ACID AS A BIOSYNTHETIC PRECURSOR OF LYCOPODINE , 1996 .

[197]  Y. Obara,et al.  Complanadine B, obscurumines A and B, new alkaloids from two species of Lycopodium , 2005 .

[198]  J. Inanaga,et al.  A Mild and Convenient Method for the Reduction of Organic Halides by Using a SmI2-THF Solution in the Presence of Hexamethylphosphoric Triamide (HMPA) , 1987 .

[199]  W. Ayer,et al.  Lycoflexine, a new type of lycopodium alkaloid , 1973 .

[200]  J. Falck,et al.  Application of copper(I)-induced thiophenoxide removal to ring expansions or chain extensions of aldehydes and ketones. Detection, Isolation, and independent preparation of the .alpha.-epoxy thioether intermediate , 1975 .

[201]  J. Kobayashi,et al.  Serratezomines D and E, new Lycopodium alkaloids from Lycopodium serratum var. serratum. , 2009, Bioorganic & medicinal chemistry letters.

[202]  G. Kraus,et al.  Bridgehead intermediates in organic synthesis: two direct syntheses of (.+-.)-lycopodine , 1985 .

[203]  Xiaoguang Lei,et al.  Total Syntheses of Lycopodium Alkaloids ( + )-Fawcettimine , ( + )-Fawcettidine , and ( )-8-Deoxyserratinine * * , 2011 .

[204]  H. Takayama,et al.  Lycopodium alkaloids: isolation and asymmetric synthesis. , 2012, Topics in current chemistry.

[205]  E. Giacobini,et al.  Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat , 1989, Journal of neuroscience research.

[206]  M. Nishizawa,et al.  Organoselenium chemistry. A facile one-step synthesis of alkyl aryl selenides from alcohols , 1976 .

[207]  A. Orechoff Untersuchung einiger Heil‐ und Giftpflanzen der UdSSR. auf deren Alkaloidgehalt , 1934 .

[208]  H. Morita,et al.  Serratezomines A--C, new alkaloids from Lycopodium serratum var. serratum. , 2000, The Journal of organic chemistry.

[209]  G. Molander Application of lanthanide reagents in organic synthesis , 1992 .

[210]  Y. Kita,et al.  New perspective for natural products synthesis: concise synthesis of (+)-sch 642305 by chiral auxiliary multiuse methodology. , 2007, Organic letters.

[211]  R. Gupta,et al.  Biosynthesis of lycopodine. Incorporation of pelletierine , 1970 .

[212]  Yujia Dai,et al.  CARBOCYCLIC RING CONSTRUCTION VIA AN INTRAMOLECULAR DIELS-ALDER REACTION OF AN IN SITU-GENERATED, HETEROATOM-STABILIZED ALLYL CATION : TOTAL SYNTHESIS OF ()-LYCOPODINE , 1998 .

[213]  H. Morita,et al.  New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium , 2004 .

[214]  T. Katoh,et al.  A novel enantioselective synthesis of the key intermediate of (−)-huperzine a employing asymmetric palladium-catalyzed bicycloannulation , 1997 .

[215]  D. Schumann,et al.  Synthese des Lycopodium-Alkaloids rac-α-Obscurin durch 1,3-Anellierung eines Enimins , 1983 .

[216]  T. Harayama,et al.  Total synthesis of the lycopodium alkaloid dl-serratinine. , 1975 .

[217]  P. G. Gassman,et al.  Acrolein acetals as allyl cation precursors in the ionic Diels-Alder reaction , 1987 .

[218]  D. E. Ward,et al.  A general method for the selective reduction of ketones in the presence of enones. , 1988 .

[219]  J. N. Johnston,et al.  Total synthesis of the lycopodium alkaloid (+)-serratezomine A. , 2009, Journal of the American Chemical Society.

[220]  C. Fan,et al.  Lycodine-Type Alkaloids from Lycopodium casuarinoides , 2006 .

[221]  Robert V. Gerard,et al.  Fastigiatine, a lycopodium alkaloid with a new ring system , 1986 .

[222]  L. Overman,et al.  Origin of stereocontrol in the construction of the 12-oxatricyclo[6.3.1.0(2,7)]dodecane ring system by Prins-pinacol reactions. , 2010, The Journal of organic chemistry.

[223]  D. Flynn,et al.  A mild two-step method for the hydrolysis of lactams and secondary amides , 1983 .

[224]  Y. Tu,et al.  Total synthesis of (±)-alopecuridine and its biomimetic transformation into (±)-sieboldine A. , 2011, Angewandte Chemie.

[225]  H. Takayama,et al.  A divergent approach for the total syntheses of cernuane-type and quinolizidine-type Lycopodium alkaloids , 2009 .

[226]  Abram Axelrod,et al.  Synthesis of (+)-complanadine A, an inducer of neurotrophic factor excretion. , 2010, Journal of the American Chemical Society.

[227]  G. Kraus,et al.  The total synthesis of lycopodine using bridgehead intermediates , 1987 .

[228]  Karl Bödeker Lycopodin, das erste Alkaloïd der Gefässkryptogamen , 1881 .

[229]  Tao Xu,et al.  Application of the Helquist annulation in Lycopodium alkaloid synthesis: unified total syntheses of (-)-8-deoxyserratinine, (+)-fawcettimine, and (+)-lycoflexine. , 2011, The Journal of organic chemistry.

[230]  S. Kirsch,et al.  Gold(I)-catalyzed divergence in the reactivity of 3-silyloxy 1,6-enynes: pinacol-terminated vs claisen-terminated cyclization cascades. , 2008, Organic letters.

[231]  E. Leistner,et al.  Stereochemistry of reactions catalysed by l-lysine decarboxylase and diamine oxidase , 1979 .

[232]  Chunnian He,et al.  A New Alkaloid from Lycopodium japonicum Thunb. , 2008 .

[233]  Karl M. Smith,et al.  Total synthesis of (±)-fawcettimine (Burnell's base A) , 1986 .

[234]  Yan Xia,et al.  Synthesis of Huperzine A and Its Analogues and Their Anticholinesterase Activity , 1991 .