A Longitudinal Study of Alkaloid Synthesis Reveals Functional Group Interconversions as Bad Actors

Chemical Reviews

Volumn 115, Issue 17, 2015, Pages 9465-9531

  Crossley, Steven W M ^a   Shenvi, Ryan A ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOIDS; MOLECULES;

ALKALOID SYNTHESIS; CHEMICAL THEORIES; INTERCONVERSIONS; LONGITUDINAL STUDY; MODERN TECHNIQUES; STEREOCENTERS; STEREOGENIC CENTERS; SYNTHETIC CHEMISTS;

SYNTHESIS (CHEMICAL);

ALKALOID;

PROCEDURES; SYNTHESIS; TRENDS;

ALKALOIDS; CHEMISTRY TECHNIQUES, SYNTHETIC;

EID: 84941114577     PISSN: 00092665     EISSN: 15206890     Source Type: Journal    
DOI: 10.1021/acs.chemrev.5b00154     Document Type: Review

References (291)

1. This historical section was compiled from an extraordinary book on alkaloids: Hesse, M. Alkaloids: Natures Curse or Blessing; Verlag Helvetica Chimica Acta: Zürich, and Wiley-VCH: Weinheim, 2002.
2. Marcet, A. An Essay on the Chemical History and Medical Treatment of Calculous Disorders; London, 1817.
3. Pelletier, P. J.; Magendie, F. Recherches chimiques et physiologiques sur lipecacuanha Ann. Chim. Phys. 1817, 4, 172-185
4. Pelletier, P. J.; Caventou, J. B. Note sur un nouvel alkalai Ann. Chim. Phys. 1818, 8, 323-324
5. Oersted, H. C. Über das Piperin, ein neues Pflanzenalkaloid J. Chem. Phys. 1820, 29, 80-82
6. Pelletier, P. J.; Caventou, J. B. Recherches chimiques sur les quinquinas Ann. Chim. Phys. 1820, 15, 289-318
7. Pelletier, P. J.; Caventou, J. B. Recherches chimiques sur les quinquinas Ann. Chim. Phys. 1820, 15, 337-365
8. Runge, F. F. Neueste phytochemische Entdeckungen zur Begründung einer wissenschaftlichen Phytochemie; G. Reimer: Berlin, 1820; pp 144-159.
9. Garson, M. J.; Simpson, J. S. Marine isocyanides and related natural products-structure, biosynthesis and ecology Nat. Prod. Rep. 2004, 21, 164-179
10. Pronin, S. V.; Shenvi, R. A. Synthesis of a Potent Antimalarial Amphilectene J. Am. Chem. Soc. 2012, 134, 19604-19606
11. Pronin, S. V.; Reiher, C. A.; Shenvi, R. A. Stereoinversion of Tertiary Alcohols to Tertiary-Alkyl Isonitriles and Amines Nature 2013, 501, 195-199
12. Shenvi, R. A.; Schnermann, M. J. Syntheses and Biological Studies of Marine Terpenoids Derived from Inorganic Cyanide Nat. Prod. Rep. 2015, 32, 543-577
13. Ladenburg, A. Synthese der activen Coniine Ber. Dtsch. Chem. Ges. 1886, 19, 2578-2583
14. Orteca, N.; Tang, D.-T. D.; Urban, S.; Zhao, D.; Glorius, F. Ruthenium-NHC Catalyzed Asymmetric Hydrogenation of Indolizines: Access to Indolizidine Alkaloids Angew. Chem., Int. Ed. 2013, 52, 9500-9503
15. Prelog, V.; Szpilfogel, S. Über Cyclopentano-2,3-pyrrolidin Helv. Chim. Acta 1945, 28, 178-182
16. Urbach, H.; Henning, R. Eine einfache diastereoselektive synthese von (1SR, 3SR, 5SR)-2-azabicyclo[3.3.0]-octan-3-carbonsäure Tetrahedron Lett. 1985, 26, 1839-1842
17. Ortiz, C.; Greenhouse, R. The total synthesis of (±)-isoretronecanol from pyrrole Tetrahedron Lett. 1985, 26, 2831-2832
18. Barluenga, J.; Tomas, M.; Kouznetsov, V.; Rubio, E. An extremely short, stereoselective synthesis of (±)-tetraponerine-8 J. Org. Chem. 1994, 59, 3699-3700
19. Scheiper, B.; Glorius, F.; Leitner, A.; Fürstner, A. Catalysis-based enantioselective total synthesis of the macrocyclic spermidine alkaloid isooncinotine Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 11960-11965
20. Glorius, F.; Spielkamp, N.; Holle, S.; Goddard, R.; Lehmann, C. W. Efficient Asymmetric Hydrogenation of Pyridines Angew. Chem., Int. Ed. 2004, 43, 2850-2852
21. Laurent, M. A. Ueber das Hydrobenzamid Ann. Chem. 1837, 21, 130-134
22. Laurent, M. A. Ueber das Amarin und einige andere Producte der bittern Mandeln Ann. Chem. 1845, 36, 1-10
23. Fownes, G. Ueber eine neue organische Base aus Bittermandelöl Ann. Chem. 1845, 54, 363-369
24. Bertagnini, C. Ueber die Bildung von Amarin, Furfurin und einer neuen Base, des Anisins Ann. Chem. 1853, 88, 127-129
25. Schlenk, W.; Bergmann, E. Über Additionsprodukte von Natrium an Kohlenstoff-Stickstoff- und Stickstoff-Stickstoff-Doppelbindungen Ann. Chem. 1928, 463, 281-322
26. Japp, F. R.; Robinson, H. H. On the constitution of amarine and lophine J. Chem. Soc., Trans. 1882, 41, 323-329
27. Corey, E. J.; Kühnle, F. N. M. A simplified synthesis of (±)-1,2-diphenyl-1,2-diaminoethane (1) from benzaldehyde and ammonia. Revision of the structures of the long-known intermediates hydrobenzamide and amarine Tetrahedron Lett. 1997, 38, 8631
28. Arend, M.; Westermann, B.; Risch, N. Modern Variants of the Mannich Reaction Angew. Chem., Int. Ed. 1998, 37, 1044-1070
29. Blicke, F. F. The Mannich Reaction Org. React. (Hoboken, NJ, U. S.) 1942, 1, 303-341
30. van Marie, C. M.; Tollens, B. Ueber Formaldehyd-Derivate des Acetophenons Ber. 1903, 36, 1351-1357
31. Schäfer, H.; Tollens, B. Ueber die Bildung von Basen aus Acetophenon, Formaldehyd und Chlorammonium Ber. Dtsch. Chem. Ges. 1906, 39, 2181-2189
32. Mannich, C.; Krösche, W. Ueber ein Kondensationsprodukt aus Formaldehyd, Ammoniak und Antipyrin Arch. Pharm. 1912, 250, 647-667
33. Borodin, A. Ueber die Einwirkung des Natriums auf Valeraldehyd J. Prakt. Chem. 1864, 93, 413-425
34. Podlech, J. "Try and Fall Sick"-The Composer, Chemist, and Surgeon Aleksandr Borodin Angew. Chem., Int. Ed. 2010, 49, 6490-6495
35. Dewick, P. M. Medicinal Natural Products: A Biosynthetic Approach; Wiley: Chichester, U.K, 2009.
36. Sir Robert Robinson-Biographical. http://www.nobelprize.org/nobel-prizes/chemistry/laureates/1947/robinson-bio.html (accessed March 5, 2015)
37. Medley, J. W.; Movassaghi, M. Robinsons landmark synthesis of tropinone Chem. Commun. 2013, 49, 10775-10777
38. Robinson, R. A synthesis of tropinone J. Chem. Soc., Trans. 1917, 111, 762-768
39. Lapworth, A. Mem. Proc.-Manchester Lit. Philos. Soc. 1920, 64, 1
40. Lapworth, A. A theoretical derivation of the principle of induced alternate polarities J. Chem. Soc. 1922, 121, 416-427
41. Evans, D. A. An Organizational Format for the Classification of Functional Groups. Application to the Construction of Difunctional Relationships. Chemistry 206: Advanced Organic Chemistry, Handout 27A; Harvard University, 2001.
42. Schöpf, C. Die Synthese von Naturstoffen, insbesondere von Alkaloiden, unter physiologischen Bedingungen. und ihre Bedeutung fiir die Frage der Entstehung einiger pflanzlicher Naturstoffe in der Zelle Angew. Chem. 1937, 50, 779-790
43. Leete, E.; Marion, L.; Spenser, I. D. Biogenesis of hyoscyamine Nature 1954, 174, 650-651
44. Leete, E.; Kim, S. H. A revision of the generally accepted hypothesis for the biosynthesis of the tropane moiety of cocaine J. Am. Chem. Soc. 1988, 110, 2976-2978
45. Robinson, R. LXXV.-A theory of the mechanism of the phytochemical synthesis of certain alkaloids J. Chem. Soc., Trans. 1917, 111, 876-899
46. Verkade, J. M. M.; van Hemert, L. J. C.; Quaedflieg, P. J. L. M.; Rutjes, F. P. J. T. Organocatalysed asymmetric Mannich reactions Chem. Soc. Rev. 2008, 37, 29-41
47. Corey, E. J.; Balanson, R. D. A total synthesis of (±)-porantherine J. Am. Chem. Soc. 1974, 96, 6516-6517
48. Siengalewicz, P.; Mulzer, J.; Rinner, U. Lycopodium Alkaloids-Synthetic Highlights and Recent Developments. In The Alkaloids; Wiley: Chichester, U.K., 2013; Vol. 72.
49. Heathcock, C. H.; Kleinman, E.; Binkley, E. S. A highly efficient synthesis of (±)-lycopodine J. Am. Chem. Soc. 1978, 100, 8036-8037
50. Heathcock, C. H.; Kleinman, E.; Binkley, E. S. Total synthesis of lycopodium alkaloids: (±)-lycopodine, (±)-lycodine, and (±)-lycodoline J. Am. Chem. Soc. 1982, 104, 1054-1068
51. Liau, B. B.; Shair, M. D. Total synthesis of (+)-fastigiatine J. Am. Chem. Soc. 2010, 132, 9594-9595
52. Lee, A. S.; Liau, B. B.; Shair, M. D. A Unified Strategy for the Synthesis of 7-Membered-Ring-Containing Lycopodium Alkaloids J. Am. Chem. Soc. 2014, 136, 13442-13452
53. Hofmann, A. W. Zur Kenntniss der Coniin-Gruppe Ber. Dtsch. Chem. Ges. 1885, 18, 5-23
54. Lellmann, E. Ueber die Coniceïne Ber. Dtsch. Chem. Ges. 1890, 23, 2141-2142
55. Daly, J. W.; Spande, T. F.; Garraffo, H. M. Alkaloids from Amphibian Skin: A Tabulation of Over Eight-Hundred Compounds J. Nat. Prod. 2005, 68, 1556-1575
56. Corey, E. J.; Hertler, W. R. The Synthesis of Dihyrdoconessine. A Method for Functionalizing Steroids at C18 J. Am. Chem. Soc. 1958, 80, 2903-2904
57. Corey, E. J.; Hertler, W. R. The Synthesis of Dihydroconessine J. Am. Chem. Soc. 1959, 81, 5209-5212
58. Buchschacher, P.; Kalvoda, J.; Arigoni, D.; Jeger, O. Direct Introduction of a Nitrogen Function at C-18 in a Steroid J. Am. Chem. Soc. 1958, 80, 2905-2906
59. Corey, E. J.; Arnett, J. F.; Widiger, G. N. A simple total synthesis of (±)-perhydrohistrionicotoxin J. Am. Chem. Soc. 1975, 97, 430-431
60. Barton, D. H. R.; Beaton, J. M.; Geller, L. E.; Pechet, M. M. A New Photochemical Reaction J. Am. Chem. Soc. 1960, 82, 2640-2641
61. Cherney, E. C.; Lopchuk, J. M.; Green, J. S.; Baran, P. S. A Unified Approach to ent-Atisane Diterpenes and Related Alkaloids: Synthesis of (-)-Methyl Atisenoate, (-)-Isoatisine, and the Hetidine Skeleton J. Am. Chem. Soc. 2014, 136, 12592-12595
62. Francisco, C. G.; Herrera, A. J.; Suárez, E. Intramolecular Hydrogen Abstraction Reaction Promoted by N-Radicals in Carbohydrates. Synthesis of Chiral 7-Oxa-6-azabicyclo[3.2.1]octane Ring Systems J. Org. Chem. 2003, 68, 1012-1017
63. Woodward, R. B.; Bader, F. E.; Bickel, H.; Frey, A. J.; Kierstead, R. W. The total synthesis of reserpine Tetrahedron 1958, 2, 1-57
64. Woodward, R. B.; Bader, F. E.; Bickel, H.; Frey, A. J.; Kierstead, R. W. The Total Synthesis of Reserpine J. Am. Chem. Soc. 1956, 78, 2023-2025
65. Woodward, R. B.; Bader, F. E.; Bickel, H.; Frey, A. J.; Kierstead, R. W. A Simplified Route to a Key Intermediate in the Total Synthesis of Reserpine J. Am. Chem. Soc. 1956, 78, 2657-2657
66. Boger, D. L.; Panek, J. S. Inverse Electron Demand Diels-Alder Reactions of Heterocyclic Azadienes: Formal Total Synthesis of Streptonigrin J. Am. Chem. Soc. 1985, 107, 5745-5754
67. Heathcock, C. H. The Enchanting Alkaloids of Yuzuriha Angew. Chem., Int. Ed. 1992, 31, 665-681
68. 20-Diterpenoid Alkaloids. A Concise Synthesis of Nominine via Oxidoisoquinolinium-1,3-Dipolar and Dienamine-Diels-Alder Cycloadditions J. Am. Chem. Soc. 2006, 128, 8734-8735
69. Müller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Hydroamination: Direct Addition of Amines to Alkenes and Alkynes Chem. Rev. 2008, 108, 3795-3892
70. Pronin, S. V.; Tabor, M. G.; Jansen, D. J.; Shenvi, R. A. A Stereoselective Hydroamination Transform to Access Polysubstituted Indolizidines J. Am. Chem. Soc. 2012, 134, 2012-2015
71. Seayad, J.; Tillack, A.; Hartung, C. G.; Beller, M. Base-Catalyzed Hydroamination of Olefins: An Environmentally Friendly Route to Amines Adv. Synth. Catal. 2002, 344, 795-813
72. Danforth, J. D. French Patent 917060, 1946.
73. Danforth, J. D. Canadian Patent 461783, 1949.
74. Danforth, J. D. U.S. Patent 2,449,644, 1948.
75. Weston, A. W. U.S. Patent 2,437,984, 1948.
76. Howk, W.; Little, E. L.; Scott, S. L.; Whitman, G. M. Alkali Metal-catalyzed Amination of Olefins J. Am. Chem. Soc. 1954, 76, 1899-1902
77. Evans, D. A.; Weber, A. E. Synthesis of the Cyclic Hexapeptide Echinocandin D. New Approaches to the Asymmetric Synthesis of β-Hydroxy α-Amino Acids J. Am. Chem. Soc. 1987, 109, 7151-7157
78. Arredondo, V. M.; Tian, S.; McDonald, F. E.; Marks, T. J. Organolanthanide-Catalyzed Hydroamination/Cyclization. Efficient Allene-Based Transformations for the Syntheses of Naturally Occurring Alkaloids J. Am. Chem. Soc. 1999, 121, 3633-3639
79. Müller, T. E.; Beller, M. Metal-Initiated Amination of Alkenes and Alkynes Chem. Rev. 1998, 98, 675-703
80. Schlott, R. J.; Falk, J. C.; Narducy, K. W. Lithium Amide Catalyzed Amine-Olefin Addition Reactions J. Org. Chem. 1972, 37, 4243-4245
81. Parker, K. A.; Fokas, D. Convergent Synthesis of (±)-dihydroisocodeine in 11 steps by the tandem radical cyclization strategy. A Formal Total Synthesis of (±)-morphine J. Am. Chem. Soc. 1992, 114, 9688-9689
82. Trauner, D.; Bats, J. W.; Werner, A.; Mulzer, J. Synthesis of Enantiomerically Pure Morphine Alkaloids: The Hydrophenanthrene Route J. Org. Chem. 1998, 63, 5908-5918
83. Mulzer, J.; Bats, J. W.; List, B.; Opatz, T.; Trauner, D. The Phenanthrenone Approach to Opium Alkaloids: Formal Total Synthesis of Morphine by Sigmatropic Rearrangement Synlett 1997, 441-444
84. Mulzer, J.; Duerner, G.; Trauner, D. Formal Total Synthesis of (-)-Morphine by Cuprate Conjugate Addition Angew. Chem., Int. Ed. Engl. 1996, 2830-2832
85. Nagata, H.; Miyazawa, N.; Ogasawara, K. A Concise Route to (-)-morphine Chem. Commun. 2001, 1094-1095
86. Nagata, H.; Miyazawa, N.; Ogasawara, K. Tandem Single-Step Construction of Chiral Haxahydrophenanthrenes: A Concise Route to (+)-Ferruginol Org. Lett. 2001, 3, 1737-1740
87. Trost, B. M.; Tang, W.; Toste, F. D. Divergent Enantioselective Synthesis of (-)-Galanthamine and (-)-Morphine J. Am. Chem. Soc. 2005, 127, 14785-14803
88. Jansen, D. J.; Shenvi, R. A. Synthesis of (-)-Neothiobinupharidine J. Am. Chem. Soc. 2013, 135, 1209-1212
89. 13C Nuclear Magnetic Resonance of Piperidine Nuphar Alkaloids J. Org. Chem. 1977, 42, 2113-2118
90. Iwasaki, K.; Wan, K. K.; Oppedisano, A.; Crossley, S. W. M.; Shenvi, R. A. Simple, Chemoselective Hydrogenation with Thermodynamic Stereocontrol J. Am. Chem. Soc. 2014, 136, 1300-1303
91. Overman, L. E.; Sworin, M.; Burk, R. M. Synthesis applications of aza-Cope rearrangements. Part 10. A new approach for the total synthesis of pentacyclic Aspidosperma alkaloids. Total synthesis of dl-16-methoxytabersonine J. Org. Chem. 1983, 48, 2685-2690
92. Zeng, Y.; Aubé, J. An expeditious total synthesis of (±)-stenine J. Am. Chem. Soc. 2005, 127, 15712-15713
93. Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis; Wiley: New York, 1995.
94. Yunusov, S. Y.; Akramov, S. T. Alkaloids of seeds of Lolium cuneatum Zh. Obshch. Khim. 1955, 25, 1813-1820
95. Akramov, S. T.; Yunusov, S. Y. Structure of norloline, loline, and lolinine Khim. Prir. Soedin. 1965, 4, 262-271
96. Cunningham, I. J. A note on the cause of tall fescue lameness in cattle Aust. Vet. J. 1949, 25, 27-28
97. Yates, S. G. Toxicity of tall fescue forage: A review Econ. Bot. 1962, 16, 295-303
98. Jacobson, D. R.; Cam, S. B.; Hutton, R. H.; Brucker, R. C.; Graden, A. P.; Dowden, D. R.; Miller, W. M. Growth, physiological responses, and evidence of toxicity in yearling dairy cattle grazing different grasses J. Dairy Sci. 1970, 53, 575-587
99. Williams, D. J.; Tyler, D. E.; Papp, E. Abdominal fat necrosis as a herd problem in Georgia cattle J. Am. Vet. Med. Assoc. 1969, 154, 1017-1021
100. Forney, M. M.; Williams, D. J.; Papp, E. M.; Tyler, D. E. Limited survey of Georgia cattle for fat necrosis J. Am. Vet. Med. Assoc. 1969, 155, 1603-1604
101. Schardl, C. L.; Grossman, R. B.; Nagabhyru, P.; Faulkner, J. R.; Mallik, U. P. Loline alkaloids: Currencies of mutualism Phytochemistry 2007, 68, 980-996
102. Jacobson, D. R.; Miller, W. M.; Seath, D. M.; Yates, S. G.; Tookey, H. L.; Wolff, I. A. Nature of fescue toxicity and progress toward identification of the toxic entity J. Dairy Sci. 1963, 46, 416-422
103. Spiering, M. J.; Moon, C. D.; Wilkinson, H. H.; Schardl, C. L. Gene Clusters for Insecticidal Loline Alkaloids in the Grass-Endophytic Fungus Neotyphodium uncinatum Genetics 2005, 169, 1403-1414
104. Glass, R. S.; Deardorff, D. R.; Gains, L. H. Synthesis and Diels Alder reaction of 2,3-dihydro-2,3-dimethylene-1,4-benzodioxin Tetrahedron Lett. 1978, 33, 2965-2968
105. Wilson, S. R.; Sawicki, R. A.; Huffman, J. C. Synthetic and Structural Studies of the Lolium Alkaloids J. Org. Chem. 1981, 46, 3887-3891
106. Tufariello, J. J.; Meckler, H.; Winzenberg, K. Synthesis of the Lolium Alkaloids J. Org. Chem. 1986, 51, 3556-3557
107. Tufariello, J. J.; Lee, G. E. Functionalized Nitrones. A Highly Stereoselective and Regioselective Synthesis of dl-Retronecine J. Am. Chem. Soc. 1980, 102, 373-374
108. Blakemore, P. R.; Schulze, V. K.; White, J. D. Asymmetric Synthesis of (+)-loline Chem. Commun. 2000, 1263-1264
109. Blakemore, P. R.; Kim, S.-K.; Schulze, V. K.; White, J. D.; Yokochi, A. F. T. Asymmetric Synthesis of (+)-loline, a Pyrrolizidine Alkaloid from rye grass and tall fescue J. Chem. Soc., Perkin Trans. 1 2001, 1831-1847
110. Naruse, M.; Aoyagi, S.; Kibayashi, C. New Chiral Route to (-)-Swainsonine via an Aqueous Acylnitroso Cycloaddition Approach J. Org. Chem. 1994, 59, 1358-1364
111. Li, G.; Chang, H.-T.; Sharpless, K. B. Catalytic Asymmetric Aminohydroxylation (AA) of Olefins Angew. Chem., Int. Ed. Engl. 1996, 35, 451-454
112. Hovey, M. T.; Eklund, E. J.; Pike, R. D.; Mainkar, A. A.; Scheerer, J. R. Synthesis of (±)-Acetylnorloline via Stereoselective Tethered Aminohydroxylation Org. Lett. 2011, 13, 1246-1249
113. Miller, K. E.; Wright, A. J.; Olesen, M. K.; Hovey, M. T.; Scheerer, J. R. Stereoselective synthesis of (+)-loline alkaloid skeleton J. Org. Chem. 2015, 80, 1569-1579
114. Blake, J.; Willson, C. D.; Rapoport, H. 3-pyrrolidinones by Intramolecular Condensation J. Am. Chem. Soc. 1964, 86, 5293-5299
115. Williams, R. M.; Cao, J. H.; Tsujishima, H.; Cox, R. J. Asymmetric, Stereocontrolled Total Synthesis of Paraherquamide A J. Am. Chem. Soc. 2003, 125, 12172-12178
116. Chincholkar, P. M.; Kale, A. S.; Gumaste, V. K.; Deshmukh, A. An efficient formal synthesis of (S)-dapoxetine from enantiopure 3-hydroxy azetidin-2-one Tetrahedron 2009, 65, 2605-2609
117. Mintz, M. J.; Walling, C. t-Butyl Hypochlorite. Organic Syntheses; Wiley: New York, 1973; Collect. Vol. 5, pp 184-187.
118. Cakmak, M.; Mayer, P.; Trauner, D. An Efficient Synthesis of Loline Alkaloids Nat. Chem. 2011, 3, 543-545
119. Tokuyama, T.; Uenoyama, K.; Brown, G.; Daly, J. W.; Witkop, B. Allenic and Acetylenic Spiropiperidine Alkaloids from the Neotropical Forg, Dendrobates histrionicus Helv. Chim. Acta 1974, 57, 2597-2604
120. Daly, J. W.; Witkop, B.; Tokuyama, T.; Nishikawa, T.; Karle, I. L. Gephyrotoxins, Histrionicotoxins and Pumiliotoxins from the Neotropical Frog Dendrobates histrionicus Helv. Chim. Acta 1977, 60, 1128-1140
121. Daly, J. W. Alkaloids of neotropical poison frogs (Dendrobatidae) Fortschr. Chem. Org. Naturst. 1982, 41, 205-340
122. Mensah-Dwumah, M.; Daly, J. W. Pharmacological activity of alkaloids from poison-dart frogs (Dendrobatidae) Toxicon 1978, 16, 189-194
123. Aronstam, R. S.; Daly, J. W.; Spande, T. F.; Narayanan, T. K.; Albuquerque, E. X. Interaction of gephyrotoxin and indolizidine alkaloids with the nicotinic acetylcholine receptor-ion channel complex of Topedo electroplax Neurochem. Res. 1986, 11, 1227-1240
124. Souccar, C.; Varanda, W. A.; Daly, J. W.; Albuquerque, E. X. Interactions of gephyrotoxin with the acetylcholine receptor-ionic channel complex. I. Blockade of the ionic channel Mol. Pharmacol. 1984, 25, 384-394
125. Souccar, C.; Varanda, W. A.; Aronstam, R. S.; Daly, J. W.; Albuquerque, E. X. Interactions of gephyrotoxin with the acetylcholine receptor-ionic channel complex. II. Enhancement of desensitization Mol. Pharmacol. 1984, 25, 395-400
126. Witkop, B.; Gossinger, E. The Alkaloids; Academic Press: New York, 1983; Vol. 21, p 205.
127. Hart, D. J. Synthesis of (±)-gephyrotoxin J. Org. Chem. 1981, 46, 3576-578
128. Ito, Y.; Nakajo, E.; Nakatsuka, M.; Saegusa, T. A new approach to gephyrotoxin Tetrahedron Lett. 1983, 24, 2881-2884
129. Pearson, W. H.; Fang, W.-K. Synthesis of Benzo-Fused 1-Azabicyclo[m.n.0]alkanes via the Schmidt Reaction: A Formal Synthesis of Gephyrotoxin J. Org. Chem. 2000, 65, 7158-7174
130. Wei, L.-L.; Hsung, R. P.; Sklenicka, H. M.; Gerasyuto, A. I. A novel and highly stereoselective intramolecular formal [3 + 3] cycloaddition reaction of vinylogous amides tethered with α,β-unsaturated aldehydes: a formal total synthesis of (+)-gephyrotoxin Angew. Chem., Int. Ed. 2001, 40, 1516-1518
131. Wei, L.-L.; Hsung, R. P.; Sklenicka, H. M.; Gerasyuto, A. I. A Novel and Highly Stereoselective Intramolecular Formal [3 + 3] Cycloaddition Reaction of Vinylogous Amides Tethered with α,β-Unsaturated Aldehydes: A Formal Total Synthesis of (+)-Gephyrotoxin Angew. Chem. 2001, 113, 1564-1566
132. Santarem, M.; Vanucci-Bacqué, C.; Lhommet, G. Formal Total Synthesis of (+)-Gephyrotoxin J. Org. Chem. 2008, 73, 6466-6469
133. Miao, L.; Shu, H.; Noble, A. R.; Fournet, S. P.; Stevens, E. D.; Trudell, M. L. An enantioselective formal synthesis of (+)-gephyrotoxin 287C ARKIVOC (Gainesville, FL, U. S.) 2010, 6, 6-14
134. Pichette, S.; Winter, D. K.; Lessard, J.; Spino, C. Converting Cycloalkanones into N-Heterocycles: Formal Synthesis of (-)-Gephyrotoxin 287C J. Org. Chem. 2013, 78, 12532-12544
135. Fujimoto, R.; Kishi, Y.; Blount, J. F. Total synthesis of (±)-gephyrotoxin J. Am. Chem. Soc. 1980, 102, 7154-7156
136. Fujimoto, R.; Kishi, Y. On the absolute configuration of gephyrotoxin Tetrahedron Lett. 1981, 22, 4197-4198
137. Corey, E. J.; Ruden, R. A. Stereoselective methods for the synthesis of terminal cis and trans enyne units Tetrahedron Lett. 1973, 1495-1499
138. Roth, M.; Dubs, P.; Gotschi, E.; Eschenmoser, A. Sulfidkontraktion via alkylative Kupplung: Eine methode zur darstellung von β-dicarbonylderivaten. Über synthetische methoden, 1. Mitteilung Helv. Chim. Acta 1971, 87, 229-734
139. Corey, E. J.; Rucker, C. Useful synthetic reagents derived from 1-triisopropylsilylpropyne and 1,3-[triisopropylsilyl]propyne, direct, stereoselective synthesis of either Z- or E- enynes Tetrahedron Lett. 1982, 719-722
140. Zhang, S.; Xu, L.; Miao, L.; Shu, H.; Trudell, M. L. General Strategy for the Construction of Enantiopure Pyrrolidine-Based Alkaloids. Total Synthesis of (-)-Monomorine J. Org. Chem. 2007, 72, 3133-3136
141. Zhang, C.; Lomenzo, S. A.; Ballay, C.; Trudell, M. L. An Improved Synthesis of (+)-2-Tropinone J. Org. Chem. 1997, 62, 7888-7889
142. Föhlisch, B.; Joachimi, R. Erzeugung und [4 + 3]-Cycloaddition von Cyclopentenylium-2-olat aus 2-Chlorcyclopentanon unter Alkoholyse-Bedingungen Chem. Ber. 1987, 120, 1951
143. Shirokane, K.; Wada, T.; Yoritate, M.; Minamikawa, R.; Takayama, N.; Sato, T.; Chida, N. Total Synthesis of (±)-Gephyrotoxin by Amide-Selective Reductive Nucleophilic Addition Angew. Chem., Int. Ed. 2014, 53, 512-516
144. Chu, S.; Wallace, S.; Smith, M. D. A Cascade Strategy Enables a Total Synthesis of (-)-Gephyrotoxin Angew. Chem., Int. Ed. 2014, 53, 13826-13829
145. DAmbrosio, M.; Guerriero, A.; Debitus, C.; Ribes, O.; Pusset, J.; Leroy, S.; Pietra, F. Agelastatin A, a New Skeleton Cytotoxic Alkaloid of the Oroidin Family. Isolation from the Axinellid Sponge Agelas dendromorpha of the Coral Sea J. Chem. Soc., Chem. Commun. 1993, 1305-1306
146. DAmbrosio, M.; Guerriero, A.; Chiasera, G.; Pietra, F. Conformational Preferences and Absolute Configuration of Agelastatin A, a Cytotoxic Alkaloid of the Axinellid Sponge Agelas dendromorpha from the Coral Sea, via Combined Molecular Modelling, NMR, and Exciton Splitting for Diamide and Hydroxyamide Derivatives Helv. Chim. Acta 1994, 77, 1895-1902
147. DAmbrosio, M.; Guerriero, A.; Ripamonti, M.; Debitus, C.; Waikedre, J.; Pietra, F. The Active Centres of Agelastatin A, a Strongly Cytotoxic Alkaloid of the Coral Sea Axinellid Spong Agelas dendromorpha Helv. Chim. Acta 1996, 79, 727-735
148. Pettit, G. R.; Ducki, S.; Herald, D. L.; Schmidt, J. M.; Chapuis, J.-C. Antineoplastic agents 470. Absolute configuration of the marine sponge bromopyrrole agelastatin A Oncol. Res. 2005, 15, 11-20
149. Hale, K. J.; Domostoj, M. M.; El-Tanani, M.; Campbell, F. C.; Mason, C. K. Strategies and Tactics in Organic Synthesis; Harmata, M., Ed.; Elsevier Academic Press: London, 2005; Vol. 6, Chapter 11, pp 352-394.
150. Mason, C. K.; McFarlane, S.; Johnston, P. G.; Crowe, P.; Erwin, P. J.; Domostoj, M. M.; Campbell, F. C.; Manaviazar, S.; Hale, K. J.; El-Tanani, M. Agelastatin A: a novel inhibitor of osteopontin-mediated adhesion, invasion, and colony formation Mol. Cancer Ther. 2008, 7, 548-558
151. Meijer, L.; Thunnissen, A. M. W. H.; White, A. W.; Garnier, M.; Nikolic, M.; Tsai, L. H.; Walter, J.; Cleverley, K. E.; Salinas, P. C.; Wu, Y. Z.; Biernat, J.; Mandelkow, E. M.; Kim, S. H.; Pettit, G. R. Inhibition of cyclin-dependent kinases, GSK-3β and CK1 by hymenialkisine, a marine sponge constituent Chem. Biol. 2000, 7, 51-63
152. Hong, T. W.; Jimenez, D. R.; Molinski, T. F. Agelastatins C and D, New Pentacyclic Bromopyrroles from the Sponge Cymbastela sp., and Potent Arthropod Toxicity of (-) Agelastatin A J. Nat. Prod. 1998, 61, 158-161
153. For formal syntheses, see refs 153-159. Hale, K. J.; Domostoj, M. M.; Tocher, D. A.; Irving, E.; Scheinmann, F. Enantiospecific Formal Total Synthesis of the Tumor and GSK-3β Inhibiting Alkaloid, (-)-Agelastatin A Org. Lett. 2003, 5, 2927-2930
154. Endeshaw, M. M.; Bayer, A.; Hansen, L. K.; Gautun, O. R. Lewis Acid-Catalyzed [4 + 2] Benzannulation between Enynal Units and Enols or Enol Ethers: Novel Synthetic Tools for Polysubstituted Aromatic Compounds Including Indole and Benzofuran Derivatives Eur. J. Org. Chem. 2006, 5249-5259
155. Menjo, Y.; Hamajima, A.; Sasaki, N.; Hamada, Y. Asymmetric Aziridination of Cyclic Enones Using Chiral Diamine Catalysts and Its Application to the Total Synthesis of (-)-Agelastatin A Org. Lett. 2011, 13, 5744-5747
156. Kano, T.; Sakamoto, R.; Akakura, M.; Maruoka, K. Stereocontrolled Synthesis of Vicinal Diamines by Organocatalytic Asymmetric Mannich Reaction of N-Protected Aminoacetaldehydes: Formal Synthesis of (-)-Agelastatin A J. Am. Chem. Soc. 2012, 134, 7516-7520
157. Behenna, D. C.; Liu, Y.; Yurino, T.; Kim, J.; White, D. E.; Virgil, S. C.; Stoltz, B. M. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams Nat. Chem. 2012, 4, 130-133
158. Shigeoka, D.; Kamon, T.; Yoshimitsu, T. Formal synthesis of (-)-agelastatin A: an iron(II)-mediated cyclization strategy Beilstein J. Org. Chem. 2013, 9, 860-865
159. Anderson, G. T.; Chase, C. E.; Koh, Y.-h.; Stien, D.; Weinreb, S. M.; Shang, M. Studies on Total Synthesis of the Cytotoxic Marine Alkaloid Agelastatin A J. Org. Chem. 1998, 63, 7594-7595
160. Stien, D.; Anderson, G. T.; Chase, C. E.; Koh, Y.-h.; Weinreb, S. M. Total Synthesis of the Antitumor Marine Sponge Alkaloid Agelastatin A J. Am. Chem. Soc. 1999, 121, 9574-9579
161. Sharpless, K. B.; Hori, T. Allylic amination of olefins and acetylenes by imido sulfur compounds J. Org. Chem. 1976, 41, 176-177
162. Bussas, R.; Kresze, G. En-Reaktionen mit Schwefeldiimiden-Struktur der En-Komponente und Reaktivität bei der Umsetzung mit Ditosylschwefeldiimid Liebigs Ann. Chem. 1980, 629-649
163. Feldman, K. S.; Saunders, J. C. Alkynyliodonium Salts in Organic Synthesis. Application to the Total Synthesis of (-)-Agelastatin A and (-)-Agelastatin B J. Am. Chem. Soc. 2002, 124, 9060-9061
164. Feldman, K. S.; Saunders, J. C.; Wrobleski, M. L. Alkynyliodonium Salts in Organic Synthesis. Development of a Unified Strategy for the Syntheses of (-)-Agelastatin A and (-)-Agelastatin B J. Org. Chem. 2002, 67, 7096-7109
165. 2 Tetrahedron Lett. 2001, 42, 4995-4999
166. 2-Transfer Agent J. Am. Chem. Soc. 1991, 113, 4571-4576
167. Hale, K. J.; Domostoj, M. M.; Tocher, D. A.; Irving, E.; Scheinmann, F. Enantiospecific Formal Total Synthesis of the Tumor and GSK-3β Inhibiting Alkaloid, (-)-Agelastatin A Org. Lett. 2003, 5, 2927-2930
168. Domostoj, M. M.; Irving, E.; Scheinmann, F.; Hale, K. J. New Total Synthesis of the Marine Antitumor Alkaloid (-)-Agelastatin A Org. Lett. 2004, 6, 2615-2618
169. Gibbs, C. F.; Hough, L.; Richardson, A. C. A new synthesis of a 2,3-epimino-α-D-allopyranoside Carbohydr. Res. 1965, 1, 290-296
170. Ali, Y.; Richardson, A. C.; Gibbs, C. F.; Hough, L. Some further ring-opening reaction of methyl 4,6-O-benzylidene-2,3-dideoxy-2,3-epimino-α-D-allopyranoside and its derivatives Carbohydr. Res. 1968, 7, 255-271
171. Bernet, B.; Vasella, A. Carbocyclische Verbindungen aus Monosacchariden. I. Umsetzungen in der Glucosereihe Helv. Chim. Acta 1979, 62, 1990-2016
172. Bernet, B.; Vasella, A. Carbocyclische Verbindungen aus Monosacchariden. II. Umsetzungen in der Mannosereihe Helv. Chim. Acta 1979, 62, 2400-2410
173. Davis, F. A.; Deng, J. Asymmetric Total Synthesis of (-)-Agelastatin A Using Sulfinimine (N-Sulfinyl Imine) Derived Methodologies Org. Lett. 2005, 7, 621-623
174. Davis, F. A.; Zhang, J.; Zhang, Y.; Qiu, H. Improved Synthesis of (-)-Agelastatin Synth. Commun. 2009, 39, 1914-1919
175. Trost, B. M.; Dong, G. New Class of Nucleophiles for Palladium-Catalyzed Asymmetric Allylic Alkylation. Total Synthesis of Agelastatin A J. Am. Chem. Soc. 2006, 128, 6054-6055
176. Trost, B. M.; Dong, G. A Stereodivergent Strategy to Both Product Enantiomers from the Same Enantiomer of a Stereoinducing Catalyst: Agelastatin A Chem.-Eur. J. 2009, 15, 6910-6919
177. Ichikawa, Y.; Yamaoka, T.; Nakano, K.; Kotsuki, H. Synthesis of (-)-Agelastatin A by [3.3] Sigmatropic Rearrangement of Allyl Cyanate Org. Lett. 2007, 9, 2989-2992
178. Yoshimitsu, T.; Ino, T.; Tanaka, T. Total Synthesis of (-)-Agelastatin A Org. Lett. 2008, 10, 5457-5460
179. Dickson, D. P.; Wardrop, D. J. Total Synthesis of (±)-Agelastatin A, A Potent Inhibitor of Osteopontin-Mediated Neoplastic Transformations Org. Lett. 2009, 11, 1341-1344
180. Deardorff, D. R.; Shambayati, S.; Myles, D. C.; Heerding, D. Studies on the Synthesis of (-)-Neplanocin A. Homochiral Preparation of a Key Cyclopentanoid Intermediate J. Org. Chem. 1988, 53, 3614-3615
181. Deardorff, D. R.; Myles, D. C. Palladium(0)-catalyzed syn-1,4-addition of carboxylic acids to cyclopentadiene monoepoxide: cis-3-acetoxy-5-hydroxycyclopent-1-ene. Organic Syntheses; Wiley: New York, 1993; Collect. Vol. VIII, p 13.
182. Wehn, P. M.; Du Bois, J. A Stereoselective Synthesis of the Bromopyrrole Natural Product (-)-Agelastatin A Angew. Chem., Int. Ed. 2009, 48, 3802-3805
183. Hama, N.; Matsuda, T.; Sato, T.; Chida, N. Total Synthesis of (-)-Agelastatin A: The Application of a Sequential Sigmatropic Rearrangement Org. Lett. 2009, 11, 2687-2690
184. Movassaghi, M.; Siegel, D. S.; Han, S. Total synthesis of all (-)-agelastatin alkaloids Chem. Sci. 2010, 1, 561-566
185. Han, S.; Siegel, D. S.; Morrison, K. C.; Hergenrother, P. J.; Movassaghi, M. Synthesis and Anticancer Activity of All Known (-)-Agelastatin Alkaloids J. Org. Chem. 2013, 78, 11970-11984
186. Reyes, J. C. P.; Romo, D. Bioinspired Total Synthesis of Agelastatin A Angew. Chem., Int. Ed. 2012, 51, 6870-6873
187. Dilley, A. S.; Romo, D. Enantioselective Strategy to the Spirocyclic Core of Palauamine and Related Bisguanidine Marine Alkaloids Org. Lett. 2001, 3, 1535-1538
188. Duspara, P. A.; Batey, R. A. A Short Total Synthesis of the Marine Sponge Pyrrole-2-aminoimidazole Alkaloid (±)-Agelastatin A Angew. Chem., Int. Ed. 2013, 52, 10862-10866
189. Garro-Helion, F.; Merzouk, A.; Guibé, F. Mild and Selective Palladium(0)-Catalyzed Deallylation of Allylic Amines. Allylamine and Diallylamine as Very Convenient Ammonia Equivalents for the Synthesis of Primary Amines J. Org. Chem. 1993, 58, 6109-6113
190. Tsuda, M.; Sasaki, M.; Mugishima, T.; Komatsu, K.; Sone, T.; Tanaka, M.; Mikami, Y.; Kobayashi, J. Scalusamides A-C, New Pyrrolidine Alkaloids from the Marine-Derived Fungus Penicillium citrinum J. Nat. Prod. 2005, 68, 273-276
191. Tsuda, M.; Kasai, Y.; Komatsu, K.; Sone, T.; Tanaka, M.; Mikami, Y.; Kobayashi, J. Citrinadin A, a Novel Pentacyclic Alkaloid from Marine-Derived Fungus Penicillium citrinum Org. Lett. 2004, 6, 3087-3089
192. Mugishima, T.; Tsuda, M.; Kasai, Y.; Ishiyama, H.; Fukushi, E.; Kawabata, J.; Watanabe, M.; Akao, K.; Kobayashi, J. Absolute Stereochemistry of Citrinadins A and B from Marine-Derived Fungus J. Org. Chem. 2005, 70, 9430-9435
193. Bian, Z.; Marvin, C. C.; Martin, S. F. Enantioselective Total Synthesis of (-)-Citrinadin A and Revision of Its Stereochemical Structure J. Am. Chem. Soc. 2013, 135, 10886-10889
194. Bian, Z.; Marvin, C. C.; Pettersson, M.; Martin, S. F. Enantioselective Total Syntheses of Citrinadins A and B. Stereochemical Revision of Their Assigned Structures J. Am. Chem. Soc. 2014, 136, 14184-14192
195. Kong, K.; Enquist, J. A.; McCallum, M. E.; Smith, G. M.; Matsumaru, T.; Menhaji-Klotz, E.; Wood, J. L. An Enantioselective Total Synthesis and Stereochemical Revision of (+)-Citrinadin B J. Am. Chem. Soc. 2013, 135, 10890-10893
196. Trost, B. M.; Rise, F. A Reductive Cyclization of 1,6- and 1,7-Enynes J. Am. Chem. Soc. 1987, 109, 3161-3163
197. Lu, B.; Li, C.; Zhang, L. Gold-Catalyzed Highly Regioselective Oxidation of C-C Triple Bonds without Acid Additives: Propargyl Moieties as Masked α,β-Unsaturated Carbonyls J. Am. Chem. Soc. 2010, 132, 14070-14072
198. Enders, D.; Zhu, J.; Raabe, G. Asymmetric Epoxidation of Enones With Oxygen in the Presence of Diethylzinc and (R,R)-N-Methylpseudoephedrine Angew. Chem., Int. Ed. Engl. 1996, 35, 1725-1728
199. Comins, D. L.; Al-awar, R. S. Model Studies toward the Synthesis of the Lycopodium Alkaloid, Phlegmarine J. Org. Chem. 1995, 60, 711-716
200. Guerrero, C. A.; Sorensen, E. J. Concise, Stereocontrolled Synthesis of the Citrinadin B Core Architecture Org. Lett. 2011, 13, 5164-5167
201. Pettersson, M.; Knueppel, D.; Martin, S. F. Concise, Stereoselective Approach to the Spirooxindole Ring System of Citrinadin A Org. Lett. 2007, 9, 4623-4626
202. McIver, A. L.; Deiters, A. Tricyclic Alkaloid Core Structures Assembled by a Cyclotrimerization-Coupled Intramolecular Nucleophilic Substitution Reaction Org. Lett. 2010, 12, 1288-1291
203. Chandler, B. D.; Roland, J. T.; Li, Y.; Sorensen, E. J. Seebachs Conjunctive Reagent Enables Double Cyclizations Org. Lett. 2010, 12, 2746-2749
204. Mundal, D. A.; Sarpong, R. Synthetic Studies toward the Citrinadin A and B Core Architecture Org. Lett. 2013, 15, 4952-4955
205. Matsumaru, T.; McCallum, M. E.; Enquist, J. A.; Smith, G. M.; Kong, K.; Wood, J. L. Synthetic studies toward the citrinadins: enantioselective preparation of an advanced spirooxindole intermediate Tetrahedron 2014, 70, 4089-4093
206. Baudoin, O.; Guenard, D.; Gueritte, F. The chemistry and biology of rhazinilam and analogues Mini-Rev. Org. Chem. 2004, 1, 333-341 and references therein.
207. Linde, H. H. A. Die Alkaloide aus Melodinus australis (F. MUELLER) PIERRE (Apocynaceae) Helv. Chim. Acta 1965, 48, 1822-1842
208. Abraham, D. J.; Rosenstein, R. D.; Lyon, R. L.; Fong, H. H. S. The structure elucidation of Rhazinilam, a new class of Alkaloids from the apocynaceae, by X-ray analysis Tetrahedron Lett. 1972, 13, 909-912
209. Gerasimenko, I.; Sheludko, Y.; Stöckigt, J. 3-Oxo-Rhazinilam: A New Indole Alkaloid from Rauvolfia serpentina × Rhazya stricta Hybrid Plant Cell Cultures J. Nat. Prod. 2001, 64, 114-116
210. Kam, T. S.; Subramaniam, G.; Chen, W. Alkaloids from Kopsia dasyrachis Phytochemistry (Elsevier) 1999, 51, 159-169
211. David, B.; Sévenet, T.; Morgat, M.; Guénard, D.; Moisand, A.; Tollon, Y.; Thoison, O.; Wright, M. Rhazinilam mimics the cellular effects of taxol by different mechanisms of action Cell Motil. Cytoskeleton 1994, 28, 317-326
212. Kholod, I.; Vallat, O.; Buciumas, A.-M.; Neier, R. Synthesis of Rhazinilam: A Comparative Review of Forty Years of Synthetic Endeavors Heterocycles 2011, 82, 917-948
213. Ratcliffe, A. H.; Smith, G. F.; Smith, G. N. The synthesis of rhazinilam Tetrahedron Lett. 1973, 14, 5179-5184
214. Johnson, J. A.; Sames, D. C-H Bond Activation of Hydrocarbon Segments in Complex Organic Molecules: Total Synthesis of the Antimitotic Rhazinilam J. Am. Chem. Soc. 2000, 122, 6321-6322
215. Johnson, J. A.; Li, N.; Sames, D. Total Synthesis of (-)-Rhazinilam: Asymmetric C-H Bond Activation via the Use of a Chiral Auxiliary J. Am. Chem. Soc. 2002, 124, 6900-6903
216. Grigg, R.; Myers, P.; Somasunderam, A.; Sridharan, V. X=Y-ZH Systems as Potential 1,3-Dipoles. Part 36. Tertiary 1,5-Electrocyclisation Processes via Oxidation of Tertiary Amines. Pyrrolo-dihydroisoquinolines and -dihydro-β-carbolines Tetrahedron 1992, 48, 9735-9744
217. II center Inorg. Chim. Acta 1998, 270, 467-478
218. Johansson, L.; Ryan, O. B.; Tilset, M. Hydrocarbon Activation at a Cationic Platinum(II) Diimine Aqua Complex under Mild Conditions in a Hydroxylic Solvent J. Am. Chem. Soc. 1999, 121, 1974-1975
219. Magnus, P.; Rainey, T. Concise synthesis of (±)-rhazinilam Tetrahedron 2001, 57, 8647-8651
220. Bowie, A. L.; Hughes, C. C.; Trauner, D. Concise Synthesis of (±)-Rhazinilam through Direct Coupling Org. Lett. 2005, 7, 5207
221. Liu, Z.; Wasmuth, A. S.; Nelson, S. G. Au(I)-Catalyzed Annulation of Enantioenriched Allenes in the Enantioselective Total Synthesis of (-)-Rhazinilam J. Am. Chem. Soc. 2006, 128, 10352
222. Zhu, C.; Shen, X.; Nelson, S. G. Cinchona Alkaloid-Lewis Acid Catalyst Systems for Enantioselective Ketene-Aldehyde Cycloadditions J. Am. Chem. Soc. 2004, 126, 5352-5353
223. Banwell, M. G.; Edwards, A. J.; Jolliffe, K. A.; Smith, J. A.; Hamel, E.; Verdier-Pinard, P. Total synthesis of (±)-rhazinal, an alkaloidal spindle toxin from Kopsia teoi Org. Biomol. Chem. 2003, 1, 296-305
224. Banwell, M. G.; Beck, D. A. S.; Willis, A. C. Enantioselective total syntheses of the alkaloids (-)-rhazinal, (-)-rhazinilam, (-)-leuconolam and (+)-epi-leuconolam ARKIVOC (Gainesville, FL, U. S.) 2006, 3, 163-174
225. Paras, N. A.; MacMillan, D. W. C. New Strategies in Organic Catalysis: The First Enantioselective Organocatalytic Friedel-Crafts Alkylation J. Am. Chem. Soc. 2001, 123, 4370-4371
226. Gu, Z.; Zakarian, A. Total Synthesis of Rhazinilam: Axial to Point Chirality Transfer in an Enantiospecific Pd-Catalyzed Transannular Cyclization Org. Lett. 2010, 12, 4224-4227
227. Morrison, M. D.; Hanthorn, J. J.; Pratt, D. A. Synthesis of Pyrrolnitrin and Related Halogenated Phenylpyrroles Org. Lett. 2009, 11, 1051-1054
228. Birman, V. B.; Li, X. Benzotetramisole: A Remarkably Enantioselective Acyl Transfer Catalyst Org. Lett. 2006, 8, 1351-1354
229. McMurray, L.; Beck, E. M.; Gaunt, M. J. Chemical Synthesis of Aspidosperma Alkaloids Inspired by the Reverse of the Biosynthesis of the Rhazinilam Family of Natural Products Angew. Chem., Int. Ed. 2012, 51, 9288-9291
230. Cho, J.-Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E.; Smith, M. R., III. Remarkably Selective Iridium Catalysts for the Elaboration of Aromatic C-H Bonds Science 2002, 295, 305-308
231. Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. Mild Iridium-Catalyzed Borylation of Arenes. High Turnover Numbers, Room Temperature Reactions, and Isolation of a Potential Intermediate J. Am. Chem. Soc. 2002, 124, 390-391
232. Takagi, J.; Sato, K.; Hartwig, J. F.; Ishiyama, T.; Miyaura, N. Concise synthesis of (±)-rhazinilam Tetrahedron Lett. 2002, 43, 5649-5651
233. Beck, E. M.; Hatley, R.; Gaunt, M. J. Synthesis of Rhazinicine by a Metal-Catalyzed C-H Bond Functionalization Strategy Angew. Chem. 2008, 120, 3046-3049
234. Liégault, B.; Fagnou, K. Palladium-Catalyzed Intramolecular Coupling of Arenes and Unactivated Alkanes in Air Organometallics 2008, 27, 4841-4843
235. Sugimoto, K.; Toyoshima, K.; Nonaka, S.; Kotaki, K.; Ueda, H.; Tokuyama, H. Protecting-Group-Free Total Synthesis of (-)-Rhazinilam and (-)-Rhazinicine using a Gold-Catalyzed Cascade Cyclization Angew. Chem., Int. Ed. 2013, 52, 7168-7171
236. dAngelo, J.; Desmaële, D.; Dumas, F.; Guingant, A. The asymmetric Michael addition reactions using chiral imines Tetrahedron: Asymmetry 1992, 3, 459-505
237. Gualtierotti, J.-B.; Pasche, D.; Wang, Q.; Zhu, J. Phosphoric acid catalyzed desymmetrization of bicyclic bislactones bearing an all-carbon stereogenic center: Total syntheses of (-)-rhazinilam and (-)-leucomidine B Angew. Chem., Int. Ed. 2014, 53, 9926
238. Su, Y.; Zhou, H.; Chen, J.; Xu, J.; Wu, X.; Lin, A.; Yao, H. Solvent-Controlled Switchable C-H Alkenylation of 4-Aryl-1H-pyrrole-3-carboxylates: Application to the Total Synthesis of (±)-Rhazinilam Org. Lett. 2014, 16, 4884
239. 3-1,3,4-oxadiazolines derived from α,β-epoxyketones. An alternative method for the conversion of α,β-epoxyketones to alkynones and alkynals Can. J. Chem. 1978, 56, 308-315
240. Markiewicz, J. T.; Wiest, O.; Helquist, P. Synthesis of Primary Aryl Amines Through a Copper-Assisted Aromatic Substitution Reaction with Sodium Azide J. Org. Chem. 2010, 75, 4887-4890
241. van Leusen, D.; van Echten, E.; van Leusen, A. M. Synthesis of 3,4-Disubstituted Pyrroles Bearing Substituents of Electron- Withdrawing and/or Electron-Donating Nature J. Org. Chem. 1992, 57, 2245-2249
242. Yang, Y.; Bai, Y.; Sun, S.; Dai, M. Biosynthetically Inspired Divergent Approach to Monoterpene Indole Alkaloids: Total Synthesis of Mersicarpine, Leuconodines B and D, Leuconoxine, Melodinine E, Leuconolam, and Rhazinilam Org. Lett. 2014, 16, 6216-6219
243. Witkop, B.; Patrick, J. P.; Rosenblum, M. Ring Effects in Autoxidation. A New Type of Camps Reaction J. Am. Chem. Soc. 1951, 73, 2641-2647
244. Winterfeldt, E. Reaktionen an Indolderivaten, XIII. Chinolon-Derivate durch Autoxydation Liebigs Ann. Chem. 1971, 745, 23-30
245. Sugimoto, K.; Miyakawa, Y.; Tokuyama, H. Total synthesis of (-)-rhazinilam using 1,3-dipolar cycloaddition of optically active münchnone intermediate Tetrahedron 2015, 71, 3619-3624
246. 4-Tetrahydroquinolinic Acids and Hexahydroindolo[2,3-a]quinolizines from L-Aspartic Acid. Racemization on the Route to Vindoline J. Org. Chem. 1986, 51, 3882-3890
247. Su, S.; Seiple, I. B.; Young, I. S.; Baran, P. S. Total Syntheses of (±)-Massadine and Massadine Chloride J. Am. Chem. Soc. 2008, 130, 16490-16491
248. Nishimura, S.; Matsunaga, S.; Shibazaki, M.; Suzuki, K.; Furihata, K.; van Soest, R. W. M.; Fusetani, N. Massadine, a Novel Geranylgeranyltransferase Type I Inhibitor from the Marine Sponge Stylissa aff. massa Org. Lett. 2003, 5, 2255-2257
249. Grube, A.; Immel, S.; Baran, P. S.; Köck, M. Massadine Chloride: A Biosynthetic Precursor of Massadine and Stylissadine Angew. Chem., Int. Ed. 2007, 46, 6721-6724
250. Kinnel, R. B.; Gehrken, H.-P.; Swali, R.; Skoropowski, G.; Scheuer, P. J. Palauamine and Its Congeners: A Family of Bioactive Bisguanidines from the Marine Sponge Stylotella aurantium J. Org. Chem. 1998, 63, 3281-3286
251. Grube, A.; Köck, M. Structural Assignment of Tetrabromostyloguanidine: Does the Relative Configuration of the Palauamines Need Revision? Angew. Chem., Int. Ed. 2007, 46, 2320-2324
252. Seiple, I. B.; Su, S.; Young, I. S.; Nakamura, A.; Yamaguchi, J.; Jorgensen, L.; Rodriguez, R. A.; OMalley, D. P.; Gaich, T.; Köck, M.; Baran, P. S. Enantioselective Total Syntheses of (-)-Palauamine, (-)-Axinellamines, and (-)-Massadines J. Am. Chem. Soc. 2011, 133, 14710-14726
253. Su, S.; Rodriguez, R. A.; Baran, P. S. Scalable, Stereocontrolled Total Syntheses of (±)-Axinellamines A and B J. Am. Chem. Soc. 2011, 133, 13922-13925
254. Sakakura, A.; Kondo, R.; Matsumura, Y.; Akakura, M.; Ishihara, K. Rational Design of Highly Effective Asymmetric Diels-Alder Catalysts Bearing 4,4′-Sulfonamidomethyl Groups J. Am. Chem. Soc. 2009, 131, 17762-17764
255. Ma, Z.; Wang, X.; Wang, X.; Rodriguez, R. A.; Moore, C. E.; Gao, S.; Tan, X.; Ma, Y.; Rheingold, A. L.; Baran, P. S.; Chen, C. Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence Science 2014, 346, 219-224
256. Wang, X.; Ma, Z.; Lu, J.; Tan, X.; Chen, C. Asymmetric Synthesis of Ageliferin J. Am. Chem. Soc. 2011, 133, 15350-15353
257. Wang, X.; Wang, X.; Tan, X.; Lu, J.; Cormier, K. W.; Ma, Z.; Chen, C. A Biomimetic Route for Construction of the [4 + 2] and [3 + 2] Core Skeletons of Dimeric Pyrrole-Imidazole Alkaloids and Asymmetric Synthesis of Ageliferins J. Am. Chem. Soc. 2012, 134, 18834-18842
258. Rodriguez, R. A.; Barrios Steed, D.; Kawamata, Y.; Su, S.; Smith, P. A.; Steed, T. C.; Romesberg, F. E.; Baran, P. S. Axinellamines as broad-spectrum antibacterial agents: scalable synthesis and biology J. Am. Chem. Soc. 2014, 136, 15403-15413
259. Moore, R. E.; Cheuk, C.; Patterson, G. M. L. Hapalindoles: New Alkaloids from the Blue-Green Alga Hapalosiphon fontinalis J. Am. Chem. Soc. 1984, 106, 6456-6457
260. Richter, J. M.; Ishihara, Y.; Masude, T.; Whitefield, B. W.; Llamas, T.; Pohjakallio, A.; Baran, P. S. Enantiospecific Total Synthesis of the Hapalindoles, Fischerindoles, and Welwitindolinones via a Redox Economic Approach J. Am. Chem. Soc. 2008, 130, 17938-17954
261. Moore, R. E.; Cheuk, C.; Yang, X.-Q. G.; Patterson, G. M. L.; Bonjouklian, R.; Smitka, T. A.; Mynderse, J. S.; Foster, R. S.; Jones, N. D.; Swartzendruber, J. K. et al. Hapalindoles, Antibacterial and Antimycotic Alkaloids from the Cyanophyte Hapalosiphon fontinalis J. Org. Chem. 1987, 52, 1036-1043
262. Vaillancourt, V.; Albizati, K. F. Synthesis and absolute configuration of (+)-hapalindole Q J. Am. Chem. Soc. 1993, 115, 3499-3502
263. Vaillancourt, V.; Albizati, K. F. A One-step Method for the α-arylation of camphor. Synthesis of (-)-cannabidiol and (-)-cannabidiol dimethyl ether J. Org. Chem. 1992, 57, 3627-3631
264. Kinsman, A. C.; Kerr, M. A. Total Synthesis of (±)-Hapalindole Q Org. Lett. 2001, 3, 3189-3191
265. Kinsman, A. C.; Kerr, M. A. The Total Synthesis of (+)-Hapalindole Q by an Organomediated Diels-Alder Reaction J. Am. Chem. Soc. 2003, 125, 14120-14125
266. Baran, P. S.; Richter, J. M. Direct Coupling of Indoles with Carbonyl Compounds: Short, Enantioselective, Gram-Scale Synthetic Entry into the Hapalindole and Fischerindole Alkaloid Families J. Am. Chem. Soc. 2004, 126, 7450-7451
267. Richter, J. M.; Ishihara, Y.; Masuda, T.; Whitefield, B. W.; Llamas, T.; Pohjakallio, A.; Baran, P. S. Enantiospecific Total Synthesis of the Hapalindoles, Fischerindoles, and Welwitindolinones via a Redox Economic Approach J. Am. Chem. Soc. 2008, 130, 17938-17954
268. Lu, Z.; Yang, M.; Chen, P.; Xiong, X.; Li, A. Total Synthesis of Hapalindole-Type Natural Products Angew. Chem., Int. Ed. 2014, 53, 13840-13844
269. Henry, T. A.; Sharp, T. M. The alkaloids of Picralima Klaineana J. Chem. Soc. 1927, 3, 1950-1959
270. Henry, T. A. The alkaloids of Picralima Klaineana, pierre. Part II J. Chem. Soc. 1932, 5, 2759-2768
271. Kamarajan, P.; Sekar, N.; Mathuram, V.; Govindasamy, S. Antitumor effect of echitamine chloride on methylchonlonthrene induced fibrosarcoma in rats Biochem. Int. 1991, 25, 491-498
272. Saraswathi, V.; Subramanian, S.; Ramamurthy, N.; Mathuram, V.; Govindasamy, S. In vitro cytotoxicity of echitamine chloride and adriamycin on Ehrlich ascites carcinoma cell culture Med. Sci. Res. 1997, 25, 167-170
273. Keawpradub, N.; Kirby, G. C.; Steele, J. C. P.; Houghton, P. J. Antiplasmodial activity of extracts and alkaloids of three Alstonia species from Thailand Planta Med. 1999, 65, 690-694
274. Husain, K.; Jantan, I.; Kamaruddin, N.; Said, I. M.; Aimi, N.; Takayama, H. J. Methyl chanofruticosinates from leaves of Kopsia flavida Blume Phytochemistry (Elsevier) 2001, 57, 603-606
275. Husain, K.; Jantan, I.; Said, I. M.; Aimi, N.; Takayama, H. J. Two new methyl chanofruticosinates from Kopsia flavida blume Asian Nat. Prod. Res. 2003, 5, 63-67
276. Jagetia, G. C.; Baliga, M. S. Evaluation of anticancer activity of the alkaloid fraction of Alstonia scholaris (Sapthaparna) in vitro and in vivo Phytother. Res. 2006, 20, 103-109
277. Khan, M. R.; Omoloso, A. D.; Kihara, M. Antibacterial activity of Alstonia Scholaris and Leea tetramera Fitoterapia 2003, 74, 736-740
278. Gupta, R. S.; Bhatnager, A. K.; Joshi, Y. C.; Sharma, M. C.; Khushalani, V.; Kachawa, J. B. Induction of Antifertility with Lupeol Acetate in Male Albino Rats Pharmacology 2005, 75, 57-62
279. Mokry, J.; Dubravkova, L.; Sefcovic, P. Alkaloids from Vinca minor L.: Vincadine, minovine and vincorine Experientia 1962, 18, 564-564 (in German)
280. Cai, X.-H.; Tan, Q.-G.; Liu, Y.-P.; Feng, T.; Du, Z.-Z.; Li, W.-Q.; Luo, X.-D. A Cage-Monoterpene Indole Alkaloid from Alstonia scholaris Org. Lett. 2008, 10, 577-580
281. Smith, J. M.; Moreno, J.; Boal, B. W.; Garg, N. K. Cascade reactions: a driving force in akuammiline alkaloid total synthesis Angew. Chem., Int. Ed. 2015, 54, 400-412
282. Eckermann, R.; Gaich, T. The akuammiline alkaloids; origin and synthesis Synthesis 2013, 45, 2813-2823
283. Zhang, M.; Huang, X.; Shen, L.; Qin, Y. Total Synthesis of the Akuammiline Alkaloid (±)-Vincorine J. Am. Chem. Soc. 2009, 131, 6013-6020
284. Zi, W.; Xie, W.; Ma, D. Total synthesis of Akuammiline alkaloid (-)-vincorine via intramolecular oxidative coupling J. Am. Chem. Soc. 2012, 134, 9126-9129
285. Horning, B. D.; MacMillan, D. W. Nine-step enantioselective total synthesis of (-)-vincorine J. Am. Chem. Soc. 2013, 135, 6442-6445
286. Shen, L.; Zhang, M.; Wu, Y.; Qin, Y. Efficient Assembly of an Indole Alkaloid Skeleton by Cyclopropanation: Concise Total Synthesis of (±)-Minfiensine Angew. Chem., Int. Ed. 2008, 47, 3618-3621
287. Adams, G. L.; Carroll, P. J.; Smith, A. B., III. Total Synthesis of (+)-Scholarisine A J. Am. Chem. Soc. 2012, 134, 4037-4040
288. Smith, M. W.; Snyder, S. A. A Concise Total Synthesis of (+)-Scholarisine A Empowered by a Unique C-H Arylation J. Am. Chem. Soc. 2013, 135, 12964-12967
289. Adams, G. L.; Carroll, P. J.; Smith, A. B., III. Access to the Akuammiline Family of Alkaloids: Total Synthesis of (+)-Scholarisine A J. Am. Chem. Soc. 2013, 135, 519-528
290. Kuttruff, C. A.; Eastgate, M. D.; Baran, P. S. Natural product synthesis in the age of scalability Nat. Prod. Rep. 2014, 31, 419-432
291. Jansen, D. J.; Shenvi, R. A. Synthesis of Medicinally Relevant Terpenes: Reducing the Cost and Time of Drug Discovery Future Med. Chem. 2014, 6, 1127-1146