Tropine

Tropine
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 Edit this at Wikidata
MeSH Tropine
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 markN
    Key: CYHOMWAPJJPNMW-JIGDXULJSA-N X markN
  • 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
Appearance White hygroscopic crystalline powder or plates
Odor Amine-like
Density 1.045 g/cm3 at 25 °C
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
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Toxic
GHS labelling:
GHS06: ToxicGHS07: Exclamation mark
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)
  • 139 mg/kg (mouse, intraperitoneal)
  • >50 mg/kg (rabbit, intravenous)
  • 280 mg/kg (mouse, intraperitoneal)
  • >50 mg/kg (rabbit, intravenous)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X markN verify (what is checkYX markN ?)

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

Derivatives

List of derivatives that can be made from tropine:

  1. AHN 1-055 HCl: [202646-03-5] Patent: Selfsame as JHW-007 (N-butyl group). This benzhydrol aromatic entity is the same as for flunamine & vanoxerine.
  2. Atropine
  3. Atromepine
  4. Benztropine
  5. Bemesetron
  6. Butropium bromide (Coliopan®)
  7. Ciclotropium (wrong stereochemistry if employing this method)
  8. Clobenztropine
  9. D-13264 (atropine quat).
  10. Decitropine [1242-69-9]
  11. Deptropine
  12. Fentonium
  13. Flutropium bromide (wrong stereoisomer using this method of synthesis).
  14. Homatropine
  15. PG-9 [156143-26-9] Maleate salt: [155649-00-6] Synthesis: Pharmacol:
  16. Methoxytropacin HCl: [74051-44-8]
  17. Prampine [7009-65-6][citation needed]
  18. Pudafensine (by Mitsunobu inversion chemistry)
  19. SM-21 (other codenames covered too)
  20. SM-25 is the ester between tropine and clofibric acid.
  21. Tropabazate[citation needed]
  22. Tropacine
  23. Tropacocaine (by Mitsunobu inversion chemistry)
  24. Tropanserin
  25. Tropatepine
  26. Tropine benzilate ("BAT")
  27. Tropirine
  28. Tropodifene
  29. Xenytropium
  30. Zepastine
  31. 3-Perfluorophenoxytropane (PC14575207)
  32. PC46905316 (Ibuprofen) &PC16115711 (Naproxen).[citation needed]
  33. Tropine p-chlorophenoxyacetate [6658-61-3] (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. ↑ Castañer, J., Thiemer, K., Klinger, K. H., Engel, J. (1982). "D-13,264". Drugs of the Future. 7 (12): 869. doi:10.1358/dof.1982.007.12.1003955. ISSN 0377-8282.
  29. ↑ Dr August Franciscus Harms, DE1152410 (1963 to Koninklijke Pharma Fab Nv).
  30. ↑ 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. PMID 14039500.
  31. ↑ Harms August Franciscus, U.S. patent 3,119,829 (1964 to Koninklijke Pharmaceutische Fabrieken NV).
  32. ↑ Teotino, U.M . et al, Eur. J. Med. Chem .-Chim. Ther ., 1968, 3, 453 (synth, pharmacol)
  33. ↑ , GB1026640 idem Davide Della Bella, Uberto Teotino, US3436458 (1969 to Whitefin Holding Sa).
  34. ↑ DE2540633 idem Rolf Banholzer, Rudolf Bauer, Alex Heusner, Werner Schulz, U.S. patent 4,042,700 (1977 to Boehringer Ingelheim Gmbh).
  35. ↑ Chemnitius, F. (1927). "Zur Darstellung des Homatropins". Journal für Praktische Chemie. 17 (1): 142–146. ISSN 0021-8383. doi:10.1002/prac.19271170105.
  36. 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. PMID 8201605.
  37. 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. PMID 8777145.
  38. ↑ 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.
  39. ↑ 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.
  40. ↑ 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.
  41. ↑ Dan Peters, et al. WO2011092061 (to NTG Nordic Transport Group AS).
  42. 1 2 Alessandro Bartolini, et al. WO1994001435 (Abiogen Pharma SRL).
  43. ↑ Basel Gesellschaft Fuer Chemis [ch], CH202181 (1939 to Ciba), C.A. 33, 89228(1939).
  44. ↑ 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.
  45. ↑ 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.
  46. ↑ J. R. Fozard and M. W. Gittos, US4563465 (1986 to Merrell Dow Pharmaceuticals Inc.)
  47. ↑ Fozard John Richard; Gittos Maurice Ward +, GB2131420 (1984 to Merrell Toraude & Co +); CA, 101,230355
  48. ↑ DE1952206 idem J Boissier, R Ratouis, US3725415 (1973 to Ind Pour La Fab Antibiotiques).
  49. ↑ Harms, A. F., Chim. Ther., 1968, 3, 277.
  50. ↑ 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.
  51. ↑ Fedosowa; Magidson Zhurnal Obshchei Khimii, 1956, vol. 26, p. 3475, 3477; engl. Ausg. S. 3867, 3868.
  52. ↑ Laszlo Gyermek, U.S. patent 2,833,773 (1958).
  53. ↑ Abraham Weber, Jacques Jean Frossard, U.S. patent 3,700,663 (1972 to Mead Johnson & Co).
  54. ↑ Grover C. Helsley, Larry Davis, Gordon E. Olsen, U.S. patent 4,861,889 (1989 to Hoechst-Roussel Pharmaceuticals, Inc.).
  55. ↑ Zakharevskiĭ AS, Shadurskiĭ KS (1975). "[Pharmacological properties of some p-chlorophenoxyacetic acid derivatives]". Farmakologiia i Toksikologiia (in Russian). 38 (2): 154–9. PMID 1227878.