Tropine

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Tropine
Tropanol - tropine.svg
Tropine.png
Names
Preferred IUPAC name
(1R,3r,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-ol
Other names
α-Tropine; Tropanol; 3-Tropanol
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.003.986 OOjs UI icon edit-ltr-progressive.svg
MeSH Tropine
PubChem CID
UNII
  • InChI=1S/C8H15NO/c1-9-6-2-3-7(9)5-8(10)4-6/h6-8,10H,2-5H2,1H3/t6-,7+,8+ X mark.svgN
    Key: CYHOMWAPJJPNMW-JIGDXULJSA-N X mark.svgN
  • InChI=1/C8H15NO/c1-9-6-2-3-7(9)5-8(10)4-6/h6-8,10H,2-5H2,1H3/t6-,7+,8+
    Key: CYHOMWAPJJPNMW-JIGDXULJBD
  • CN1[C@@H]2CC[C@H]1C[C@H](C2)O
Properties
C8H15NO
Molar mass 141.214 g·mol−1
AppearanceWhite hygroscopic crystalline powder [1] [2] [3] or plates
Odor Amine-like [2]
Density 1.045 g/cm3 at 25 °C [2]
1.016 g/cm3 at 100 °C
Melting point 64 °C (147 °F; 337 K)
Boiling point 233 °C (451 °F; 506 K)
Solubility Very soluble in water, diethyl ether, ethanol [4]
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
Toxic
GHS labelling:
GHS-pictogram-skull.svg GHS-pictogram-exclam.svg
Danger
H301, H302, H312, H332
P261, P264, P270, P271, P280, P301+P316, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, P405, P501
Lethal dose or concentration (LD, LC):
  • >2000 mg/kg (rat, oral) [2]
  • 139 mg/kg (mouse, intraperitoneal)
  • >50 mg/kg (rabbit, intravenous)
  • 280 mg/kg (mouse, intraperitoneal)
  • >50 mg/kg (rabbit, intravenous) [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Tropine is a derivative of tropane containing a hydroxyl group at the third carbon. It is also called 3-tropanol. [4] It is a poisonous white hygroscopic crystalline powder. [3] It is a heterocyclic alcohol and an amine. [3]

Contents

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. [5]

Occurrence

Tropine is a natural product found in the plants of deadly nightshade (Atropa belladonna) and devil's trumpet (Datura stramonium). [1]

Chemistry

Synthesis

It can be prepared by hydrolysis of atropine [6] or other solanaceous alkaloids. [3] [7]

In the laboratory it is made by the reduction of tropinone: [8] Patent: [9] [10]

Derivatives

List of derivatives that can be made from tropine:

  1. AHN 1-055 HCl: [202646-03-5] [11] [12] Patent: [13] Selfsame as JHW-007 (N-butyl group). This benzhydrol aromatic entity is the same as for flunamine & vanoxerine.
  2. Atropine [14]
  3. Atromepine [15] [16]
  4. Benztropine [17] [18]
  5. Bemesetron [19] [20]
  6. Butropium bromide (Coliopan®) [21] [22]
  7. Ciclotropium (wrong stereochemistry if employing this method) [23]
  8. Clobenztropine [24] [25] [26] [27]
  9. Decitropine [1242-69-9] [28]
  10. Deptropine [29] [30]
  11. Fentonium [31] [32]
  12. Flutropium bromide (wrong stereoisomer using this method of synthesis). [33]
  13. Homatropine [34]
  14. PG-9 [156143-26-9] Maleate salt: [155649-00-6] Synthesis: [35] [36] Pharmacol: [37] [38] [39]
  15. Methoxytropacin HCl: [74051-44-8]
  16. Prampine [7009-65-6][ citation needed ]
  17. Pudafensine [40] (by Mitsunobu inversion chemistry)
  18. SM-21 (other codenames covered too) [36] [41]
  19. SM-25 is the ester between tropine and clofibric acid. [41]
  20. Tropabazate [ citation needed ]
  21. Tropacine [42] [43] [44]
  22. Tropacocaine (by Mitsunobu inversion chemistry) [6]
  23. Tropanserin [45] [46]
  24. Tropatepine [47]
  25. Tropine benzilate ("BAT")
  26. Tropirine [48] [49]
  27. Tropodifene [50]
  28. Xenytropium [51]
  29. Zepastine [52]
  30. 3-Perfluorophenoxytropane (PC14575207) [53]
  31. PC46905316 (Ibuprofen) [35] &PC16115711 (Naproxen).[ citation needed ]
  32. Tropine p-chlorophenoxyacetate [6658-61-3] [54] (c.f. Meclofenoxate).

See also

References

  1. 1 2 3 "8-Methyl-8-azabicyclo[3.2.1]octan-3-ol".
  2. 1 2 3 4 "Safety Data Sheet - Tropine". www.sigmaaldrich.com.
  3. 1 2 3 4 "Medical Definition of TROPINE".
  4. 1 2 Lide, David R. (1998), Handbook of Chemistry and Physics (87 ed.), Boca Raton, Florida: CRC Press, pp. 3–564, ISBN   0-8493-0594-2
  5. ↑ Ping, Yu; Li, Xiaodong; You, Wenjing; Li, Guoqiang; Yang, Mengquan; Wei, Wenping; Zhou, Zhihua; Xiao, Youli (10 June 2019). "Production of the Plant-Derived Tropine and Pseudotropine in Yeast". ACS Synthetic Biology. 8 (6): 1257–1262. doi:10.1021/acssynbio.9b00152. PMID   31181154. S2CID   184484993.
  6. 1 2 "[2008-09-10] Cocaine analog in two steps from native plant material". www.seanmichaelragan.com.
  7. ↑ Ladenburg, A (January 1902). "Bildung von Tropin aus Tropidin und die Synthese des Atropins". Berichte der deutschen chemischen Gesellschaft. 35 (1): 1159–1162. doi:10.1002/cber.190203501191.
  8. ↑ Beckett, AH, Harper, NJ, Balon, ADJ, Watts, THE (January 1959). "Stereochemistry of the reduction of tropinone" . Tetrahedron. 6 (4): 319–330. doi:10.1016/0040-4020(59)80012-0.
  9. ↑ Rolf Sachse & Albert Schaupp, U.S. patent 6,005,110 (1999 to Pfleger R Chemische Fabrik GmbH).
  10. ↑ Van de Kamp, Sletzinger, U.S. patent 2,366,760 (1945 to Merck & Co.)
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Amy Hauck Newman, U.S. patent 5,792,775 (1998 to US Department of Health and Human Services).
  14. ↑ Al-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.
  15. ↑ Melone, 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.
  16. ↑ 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.
  17. ↑ Richard P. Phillips, U.S. patent 2,595,405 (1952 to Merck a Co).
  18. ↑ Weijlard John, U.S. patent 2,706,198 (1952 to Merck & Co Inc).
  19. ↑ Pento, J. T. (1985). "MDL-72222" . Drugs of the Future. 10 (10): 820. doi:10.1358/dof.1985.010.10.61916. ISSN   0377-8282 . Retrieved 8 December 2025.
  20. ↑ John Richard Fozard, Maurice Ward Gittos, EP0067770 (1982 to Merrell Dow France Et Cie).
  21. ↑ 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.
  22. ↑ DE1950378 idem Satoru Tanaka, Kazunori Hasimoto, US3696110 (1972 to Gisai Kk).
  23. ↑ DE2026661 idem R Bauer, W Schulz, W Sirrenberg, G Walther US3743735 (1973 to Boehringer Sohn Ingelheim).
  24. ↑ Fromer Stephen, FR1249205 (1961).
  25. ↑ Stephen Fromer, U.S. patent 2,799,680 (1957).
  26. ↑ Dr Stephan Fromer, DE1020634 (1957 to Schenley Lab Inc).
  27. ↑ Cyril H. Meld, U.S. patent 2,782,200 (1957 to Schenley Labora).
  28. ↑ Dr August Franciscus Harms, DE1152410 (1963 to Koninklijke Pharma Fab Nv).
  29. ↑ Van Der Stelt, C., Harms, A. F., Nauta, W. Th. (September 1961). "The Effect of Alkyl-Substitution in Drugs--V. Synthesis and Chemical Properties of Some Dibenzo [a,d]1,4-cycloheptadienyl Ethers" . Journal of Medicinal and Pharmaceutical Chemistry. 4 (2): 335–349. doi:10.1021/jm50018a008.
  30. ↑ Harms August Franciscus, U.S. patent 3,119,829 (1964 to Koninklijke Pharmaceutische Fabrieken NV).
  31. ↑ Teotino, U.M . et al, Eur. J. Med. Chem .-Chim. Ther ., 1968, 3, 453 (synth, pharmacol)
  32. ↑ , GB1026640 idem Davide Della Bella, Uberto Teotino, US3436458 (1969 to Whitefin Holding Sa).
  33. ↑ DE2540633 idem Rolf Banholzer, Rudolf Bauer, Alex Heusner, Werner Schulz, U.S. patent 4,042,700 (1977 to Boehringer Ingelheim Gmbh).
  34. ↑ Chemnitius, F. (1927). "Zur Darstellung des Homatropins". Journal für Praktische Chemie. 17 (1): 142–146. ISSN 0021-8383. doi:10.1002/prac.19271170105.
  35. 1 2 Gualtieri, F., Conti, G., Dei, S., Giovannoni, M. P., Nannucci, F., Romanelli, M. N., Scapecchi, S., Teodori, E., Fanfani, L., Ghelardini, C., Giotti, A., Bartolini, A. (May 1994). "Presynaptic Cholinergic Modulators as Potent Cognition Enhancers and Analgesic Drugs. 1. Tropic and 2-Phenylpropionic Acid Esters". Journal of Medicinal Chemistry. 37 (11): 1704–1711. doi:10.1021/jm00037a022.
  36. 1 2 Romanelli, M. N., Bartolini, A., Bertucci, C., Dei, S., Ghelardini, C., Giovannini, M. G., Gualtieri, F., Pepeu, G., Scapecchi, S., Teodori, E. (1996). <225::AID-CHIR1>3.0.CO;2-G "Synthesis and enantioselectivity of the enantiomers of PG9 and SM21, new potent analgesic and cognition-enhancing drugs" . Chirality. 8 (3): 225–233. doi:10.1002/(SICI)1520-636X(1996)8:3<225::AID-CHIR1>3.0.CO;2-G.
  37. ↑ 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.
  38. ↑ 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.
  39. ↑ 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.
  40. ↑ Dan Peters, et al. WO2011092061 (to NTG Nordic Transport Group AS).
  41. 1 2 Alessandro Bartolini, et al. WO1994001435 (Abiogen Pharma SRL).
  42. ↑ Basel Gesellschaft Fuer Chemis [ch], CH202181 (1939 to Ciba), C.A. 33, 89228(1939).
  43. ↑ 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.
  44. ↑ 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.
  45. ↑ J. R. Fozard and M. W. Gittos, US4563465 (1986 to Merrell Dow Pharmaceuticals Inc.)
  46. ↑ Fozard John Richard; Gittos Maurice Ward +, GB2131420 (1984 to Merrell Toraude & Co +); CA, 101,230355
  47. ↑ DE1952206 idem J Boissier, R Ratouis, US3725415 (1973 to Ind Pour La Fab Antibiotiques).
  48. ↑ Harms, A. F., Chim. Ther., 1968, 3, 277.
  49. ↑ 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.
  50. ↑ Fedosowa; Magidson Zhurnal Obshchei Khimii, 1956 , vol. 26, p. 3475, 3477; engl. Ausg. S. 3867, 3868.
  51. ↑ Laszlo Gyermek, U.S. patent 2,833,773 (1958).
  52. ↑ Abraham Weber, Jacques Jean Frossard, U.S. patent 3,700,663 (1972 to Mead Johnson & Co).
  53. ↑ Grover C. Helsley, Larry Davis, Gordon E. Olsen, U.S. patent 4,861,889 (1989 to Hoechst-Roussel Pharmaceuticals, Inc.).
  54. ↑ Zakharevskiĭ AS, Shadurskiĭ KS (1975). "[Pharmacological properties of some p-chlorophenoxyacetic acid derivatives]". Farmakologiia I Toksikologiia (in Russian). 38 (2): 154–9. PMID   1227878.
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