Tropine is a derivative of tropane containing a hydroxyl group at the third carbon. It is also called 3-tropanol. It is a poisonous white hygroscopic crystalline powder. It is a heterocyclic alcohol and an amine.
Tropine is a central building block of many chemicals active in the nervous system, including tropane alkaloids. Some of these compounds, such as long-acting muscarinic antagonists are used as medicines because of these effects.
Occurrence Tropine is a natural product found in the plants of deadly nightshade (Atropa belladonna) and devil's trumpet (Datura stramonium).
Chemistry Synthesis It can be prepared by hydrolysis of atropine or other solanaceous alkaloids.
In the laboratory it is made by the reduction of tropinone: Patent:Rolf Sachse & Albert Schaupp, (1999 to Pfleger R Chemische Fabrik GmbH).Van de Kamp, Sletzinger, (1945 to Merck & Co.)
Derivatives List of derivatives that can be made from tropine: AHN 1-055 HCl: [202646-03-5]Newman, Amy Hauck; Allen, Andrew C.; Izenwasser, Sari; Katz, Jonathan L. (1994). "Novel 3.alpha.-(Diphenylmethoxy)tropane Analogs: Potent Dopamine Uptake Inhibitors without Cocaine-like Behavioral Profiles". Journal of Medicinal Chemistry. 37 (15): 2258–2261. doi:10.1021/jm00041a002.Newman, Amy Hauck; Kline, Richard H.; Allen, Andrew C.; Izenwasser, Sari; George, Clifford; Katz, Jonathan L. (1995). "Novel 4'-Substituted and 4',4-Disubstituted 3.alpha.-(Diphenylmethoxy)tropane Analogs as Potent and Selective Dopamine Uptake Inhibitors". Journal of Medicinal Chemistry. 38 (20): 3933–3940. doi:10.1021/jm00020a006. Patent:Amy Hauck Newman, (1998 to US Department of Health and Human Services). Selfsame as JHW-007 (N-butyl group). This benzhydrol aromatic entity is the same as for flunamine & vanoxerine. AtropineAl-Badr, A. A., Muhtadi, F. J. (1985). "Analytical Profiles of Drug Substances". Atropine. Vol. 14. Elsevier. pp. 325–389. doi:10.1016/S0099-5428(08)60585-7. AtromepineMelone, Gaetano; Vecchi, Alberto; Pagani, Giuseppe; Testa, Emilio (1960). "Notes- Tropine DL-α-Methyltropate (Methylatropine) and Its Optical Antipodes". The Journal of Organic Chemistry. 25 (5): 859–861. doi:10.1021/jo01075a624.Scarselli, Veniero; Cignarella, Giorgio; Maffii, Giulio (1964). "Structural Changes and Anticholinergic Activity in a Class of Tropic and α-Methyltropic Acid Derivatives". Journal of Medicinal Chemistry. 7 (2): 237–238. doi:10.1021/jm00332a026. BenztropineRichard P. Phillips, (1952 to Merck a Co).Weijlard John, (1952 to Merck & Co Inc). BemesetronJohn Richard Fozard, Maurice Ward Gittos, EP0067770 (1982 to Merrell Dow France Et Cie). Butropium bromide (Coliopan®)Tanaka, Satoru; Wakabayashi, Tsuneo; Hashimoto, Kazunori; Toyoshima, Shoji (1972). "Studies on Diphenyl Ether Derivatives. III. : Synthesis and Spasmolytic Screening of New Quaternary Salts of Tropine Tropates". YAKUGAKU ZASSHI. 92 (4): 510–513. doi:10.1248/yakushi1947.92.4_510. DE1950378 idem Satoru Tanaka, Kazunori Hasimoto, US3696110 (1972 to Gisai Kk). Ciclotropium (wrong stereochemistry if employing this method) DE2026661 idem R Bauer, W Schulz, W Sirrenberg, G Walther US3743735 (1973 to Boehringer Sohn Ingelheim). ClobenztropineFromer Stephen, FR1249205 (1961).Stephen Fromer, (1957).Dr Stephan Fromer, DE1020634 (1957 to Schenley Lab Inc).Cyril H. Meld, (1957 to Schenley Labora). D-13264 (atropine quat). Decitropine [1242-69-9]Dr August Franciscus Harms, DE1152410 (1963 to Koninklijke Pharma Fab Nv). Deptropine Harms August Franciscus, (1964 to Koninklijke Pharmaceutische Fabrieken NV). FentoniumTeotino, U.M . et al, Eur. J. Med. Chem .-Chim. Ther ., 1968, 3, 453 (synth, pharmacol), GB1026640 idem Davide Della Bella, Uberto Teotino, US3436458 (1969 to Whitefin Holding Sa). Flutropium bromide (wrong stereoisomer using this method of synthesis). DE2540633 idem Rolf Banholzer, Rudolf Bauer, Alex Heusner, Werner Schulz, (1977 to Boehringer Ingelheim Gmbh). Homatropine Chemnitius, F. (1927). "Zur Darstellung des Homatropins". Journal für Praktische Chemie. 17 (1): 142–146. ISSN 0021-8383. doi:10.1002/prac.19271170105. PG-9 [156143-26-9] Maleate salt: [155649-00-6] Synthesis: Pharmacol:Ghelardini, Carla; Galeotti, Nicoletta; Bartolini, Alessandro; Furukawa, Shoei; Nitta, Atsumi; Manetti, Dina; Gualtieri, Fulvio (1998). "Memory Facilitation and Stimulation of Endogenous Nerve Growth Factor Synthesis by the Acetylcholine Releaser PG-9". The Japanese Journal of Pharmacology. 78 (3): 245–251. doi:10.1254/jjp.78.245. ISSN 0021-5198.Ghelardini C, Galeotti N, Gualtieri F, Marchese V, Bellucci C, Bartolini A. Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG-9. J Pharmacol Exp Ther. 1998;284(3):806-16. PMID: 9495837.Ghelardini, C., Galeotti, N., Romanelli, M. N., Gualtieri, F., Bartolini, A. (March 2000). "Pharmacological Characterization of the Novel ACh Releaser α‐tropanyl 2‐(4‐bromophenyl)propionate (PG‐9)". CNS Drug Reviews. 6 (1): 63–78. doi:10.1111/j.1527-3458.2000.tb00138.x. Methoxytropacin HCl: [74051-44-8] Prampine [7009-65-6] PudafensineDan Peters, et al. WO2011092061 (to NTG Nordic Transport Group AS). (by Mitsunobu inversion chemistry) SM-21 (other codenames covered too)Alessandro Bartolini, et al. WO1994001435 (Abiogen Pharma SRL). SM-25 is the ester between tropine and clofibric acid. Tropabazate TropacineBasel Gesellschaft Fuer Chemis [ch], CH202181 (1939 to Ciba), C.A. 33, 89228(1939).Friess, S.L.; Reber, L.J.; Thommesen, W.C.; Greenbaum, L.J.; Standaert, F.G.; Hudak, W.V. (1960). "Toxicologic properties and stereochemical configuration in derivatives of the tropanol series". Toxicology and Applied Pharmacology. 2 (5): 574–588. ISSN 0041-008X. doi:10.1016/0041-008X(60)90024-7.XU, Rong; SIM, Meng-Kwoon; GO, Mei-Lin (1998). "Synthesis, Antimuscarinic Activity and Quantitative Structure-Activity Relationship (QSAR) of Tropinyl and Piperidinyl Esters". CHEMICAL & PHARMACEUTICAL BULLETIN. 46 (2): 231–241. doi:10.1248/cpb.46.231. Tropacocaine (by Mitsunobu inversion chemistry) Tropanserin J. R. Fozard and M. W. Gittos, US4563465 (1986 to Merrell Dow Pharmaceuticals Inc.)Fozard John Richard; Gittos Maurice Ward +, GB2131420 (1984 to Merrell Toraude & Co +); CA, 101,230355 Tropatepine DE1952206 idem J Boissier, R Ratouis, US3725415 (1973 to Ind Pour La Fab Antibiotiques). Tropine benzilate ("BAT") Tropirine Harms, A. F., Chim. Ther., 1968, 3, 277. van der Stelt C, Hofman PS, Funcke AB, Nauta WT. Synthesis and pharmacological properties of some 5H-benzo(4,5)cyclohepta(1,2-b)pyridine derivatives. Arzneimittelforschung. 1968 Jun;18(6):756-8. PMID: 4387811. Tropodifene Fedosowa; Magidson Zhurnal Obshchei Khimii, 1956 , vol. 26, p. 3475, 3477; engl. Ausg. S. 3867, 3868. XenytropiumLaszlo Gyermek, (1958). Zepastine Abraham Weber, Jacques Jean Frossard, (1972 to Mead Johnson & Co). 3-Perfluorophenoxytropane (PC14575207)Grover C. Helsley, Larry Davis, Gordon E. Olsen, (1989 to Hoechst-Roussel Pharmaceuticals, Inc.). PC46905316 (Ibuprofen) &PC16115711 (Naproxen). Tropine p-chlorophenoxyacetate [6658-61-3] (c.f. Meclofenoxate).
See also Atropine Pseudotropine Scopine Tropane alkaloid Tropinone
References