Synthesis of a tetracyclic, conformationally constrained analogue of Δ8-THC

Bioorganic and Medicinal Chemistry

Volumn 6, Issue 12, 1998, Pages 2281-2288

  Huffman, John W ^a   Yu, Shu ^a  

^a CLEMSON UNIVERSITY   (United States)

Author keywords

Cannabinoid; Cannabinoid receptor; Petrzilka synthesis; Stobbe tetralone synthesis; THC

Indexed keywords

4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; CANNABINOID; DELTA8 TETRAHYDROCANNABINOL;

ANIMAL TISSUE; ARTICLE; BRAIN; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY; INFRARED SPECTROPHOTOMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; RECEPTOR AFFINITY;

EID: 0032423378     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0968-0896(98)80008-4     Document Type: Article

References (26)

1. Gaoni, Y.; Mechoulam, R. J. Am. Chem. Soc. 1964, 86, 1646.
2. (a) Razdan, R. K. Pharmacol. Rev. 1986, 38, 75.
3. (b) Mechoulam, R.; Devane, W. A.; Glaser, R. Cannabinoid Geometry and Biological Behavior. In Marijuana/Cannabinoids: Neurobiology and Neurophysiology; Murphy, L.; Bartke, A., Eds.; CRC Press: Boca Raton, 1992; pp 1-33.
4. Huffman, J. W.; Lainton, J. A. H.; Banner, W. K.; Duncan, S. G.; Jordan, R. D.; Yu, S.; Dai, D.; Martin, B. R.; Wiley, J. L.; Compton, D. R. Tetrahedron 1997, 53, 1557.
5. Razdan, R. K.; Dalzell, H. C. J. Med. Chem. 1976, 19, 719. Although these authors describe no attempts to prepare ste-reoisomerically pure 3, the product is a crystalline solid and is probably a single isomer.
6. Edery, H.; Grunfeld, Y.; Porath, G.; Ben-Zvi, Z.; Shani, A.; Mechoulam, R. Arzneim. -Forsch. 1972, 22, 1995.
7. Petrzilka, T.; Sikemeier, C. Helv. Chim. Acta. 1967, 50, 1416.
8. (a) Huffman, J. W.; Zhang, X.; Wu, M.-J.; Joyner, H. H.; Pennington, W. T. J. Org. Chem. 1991, 56, 1481.
9. (b) Huffman, J. W.; Joyner, H. H.; Lee, M. D.; Jordan, R. D.; Pennington, W. T. J. Org. Chem. 1991, 56, 2081.
10. (c) Huffman, J. W.; Yu, S.; Showalter, V.; Abood, M. E.; Wiley, J. L.; Compton, D. R.; Martin, B. R.; Bramblett, R. D.; Reggio, P. H. J. Med. Chem. 1996, 39, 3875.
11. Cannon, J. G.; Brubaker, A. N.; Long, J. P.; Flynn, J. R.; Verimer, T.; Harnirattisai, P.; Costall, B.; Naylor, R. J.; Nohria, V. J. Med. Chem. 1981, 24, 149.
12. Johnson, W. S.; Daub, G. H. Org. React. 1951, 6, 1.
13. Horii, Z.; Katagi, T.; Tamura, Y. Chem. Pharm. Bull. 1963, 11, 309.
14. Majetich, G.; Zhang, Y.; Wheless, K. Tetrahedron Lett. 1994, 35, 8727.
15. Jung, M. E.; Lyster, M. A. J. Org. Chem. 1977, 42, 3761.
16. These experiments are described in detail in the Ph.D. dissertation of S. Yu, Clemson University, 1997.
17. Glatz, B.; Helmchen, G.; Muxfeldt, H.; Porcher, H.; Prewo, R.; Senn, J.; Stezowski, J. J.; Stojda, R. J.; White, D. K. J. Am. Chem. Soc. 1979, 101, 2171. These authors mention the preparation of thioketal 16, and the alcohol obtained upon reduction; however, the compounds are not characterized, and no experimental details are presented.
18. Fetizon, M.; Jurion, M. J. Chem. Soc., Chem. Commun. 1972, 382.
19. Brewster, J. H.; Bayer, H. O.; Osman, S. F. J. Org. Chem. 1964, 29, 110.
20. 13C NMR spectra of the two components of the mixture are virtually identical which is inconsistent with regioisomers.
21. Compton, D. R.; Rice, K. C.; DeCosta, B. R.; Razdan, R. K.; Melvin, L. S.; Johnson, M. R.; Martin, B. R. J. Pharmacol. Exp. Ther. 1993, 265, 218.
22. Martin, B. R.; Compton, D. R.; Semus, S. F.; Lin, S.; Marciniak, G.; Grzybowska, J.; Charalambous, A.; Makriyannis, A. Pharmacol. Biochem. Behav. 1993, 46, 295.
23. Lu, D.; Khanolkar, A.; Meng, Z.; Fan, P.; Reggio, P. H.; Makriyannis, A. In 1997 Symposium on Cannabinoids, International Cannabinoid Research Society, Burlington, VT, 1997, p 1. The synthesis of this analogue of 2 was very different from that described above.
24. Duncan, S. G. Ph.D. dissertation, Clemson University, 1997.
25. PCModel is a modified MM2/MMP1 program which incorporates the MODEL graphical interface and which permits the direct comparison of several structures. PCModel is marketed by Serena Software, Bloomington, IN.
26. Darcy, P. J.; Hart, R. J.; Heller, H. G. J. Chem. Soc., Perkin Trans. 1, 1978, 571. These authors report the reaction of 3,5-dimethoxybenzaldehyde with dimethyl succinate to provide an uncharacterized Stobbe product.