Synthesis of tetrahydroquinolines, hexahydrobenzoindolizines and an aryl phosphonate linker for the generation of catalytic antibodies

Abstract

Syntheses of 6-methoxy-1-methyl-1,2,3,4-tetrahydroquinoline-3-methanol 10 and 1,2,3,5,6,10b-hexahydrobenzo[g]indolizine-6-methanol 34 are described. The aryl phosphonic acid 14, which can be used as a linker to a protein, is synthesised and coupled to the above alcohols. These haptens, when linked to a protein, are intended to generate antibodies able to catalyse cationic cyclisation reactions.

References

1. D. Cane, Chem. Rev., 1990, 90, 1089.
2. (a) P. G. Schultz, Angew. Chem., Int. Ed. Engl., 1989, 28, 1283; (b) R. A. Lerner, S. J. Benkovic and P. G. Schultz, Science, 1991, 252, 659; (c) S. J. Benkovic, Annu. Rev. Biochem., 1992, 61, 29.
3. (a) T. Li, K. D. Janda, J. A. Ashley and R. A. Lerner, Science, 1994, 264, 1289; (b) T. Li, K. D. Janda, S. Hilton and R. A. Lerner, J. Am. Chem. Soc., 1995, 117, 2367.
4. I. M. Bell, C. Abell and F. J. Leeper, J. Chem. Soc., Perkin Trans. 1, 1994, 1997.
5. C. J. Cooksey and M. D. Johnson, J. Chem. Soc. B, 1968, 10, 1191.
6. T. Fujii, S. Yoshifuji, M. Michishita, M. Mitsukuchi and K. Yoshida, Chem. Pharm. Bull., 1973, 21, 2695.
7. (a) T. Hirao, T. Masunaga, Y. Ohshiro and T. Agawa, Synthesis, 1981, 56; (b) T. Hirao, T. Masunaga, N. Yamada, Y. Ohshiro and T. Agawa, Bull. Chem. Soc. Jpn., 1982, 55, 909.
8. G. A. Olah, S. C. Narang, B. G. Balaram Gupta and R. Malhotra, J. Org. Chem., 1979, 44, 1247.
9. (a) M. Mikolajczyk and P. Kielbasinski, Tetrahedron, 1981, 37, 233; (b) B. Nieses and W. Steglich, Angew. Chem., Int. Ed. Engl., 1978, 17, 522; (c) Y. S. Klausner and M. Bodansky, Synthesis, 1972, 453.
10. G. Parrinello and J. K. Stille, J. Am. Chem. Soc., 1987, 109, 7122.
11. S. H. Pine, R. J. Pettit, G. D. Geib, S. G. Cruz, C. H. Gallego, T. Tijerina and R. D. Pine, J. Org. Chem., 1985, 50, 1212.
12. L. F. Fieser and M. Fieser, Reagents for Organic Synthesis, Wiley, New York, 1967, vol. 1, p. 1179.
13. C. Lawrence, I. M. Bell, C. Abell and F. J. Leeper, Isr. J. Chem., 1996, 36, 161.
14. (a) J. C. Hubert, W. Steege, W. N. Speckamp and H. O. Huisman, Synth. Commun., 1971, 1, 103; (b) J. C. Hubert, W. N. Speckamp and H. O. Huisman, Tetrahedron Lett., 1972, 13, 4493; (c) J. C. Hubert, J. B. P. A. Wijnberg and W. N. Speckamp, Tetrahedron, 1975, 31, 437; (d) A. I. Meyers, B. A. Lefker, T. J. Sowin and L. J. Westrum, J. Org. Chem., 1989, 54, 4243.
15. (a) S. Searles, R. G. Nickerson and W. K. Witsiepe, J. Org. Chem., 1959, 24, 1839; (b) P. A. Marshall and R. H. Prager, Aust. J. Chem., 1977, 30, 141; (c) R. F. Nystrom and W. G. Brown, J. Am. Chem. Soc., 1947, 69, 1197.
16. S. Takano, M. Akiyama, S. Sato and K. Ogasawara, Chem. Lett., 1983, 1593.
17. (a) R. M. Hann, N. K. Richtmyer, H. W. Diehl and C. S. Hudson, J. Am. Chem. Soc., 1950, 72, 561; (b) H. G. Fletcher, Methods Carbohydr. Chem., 1963, 2, 307.
18. O. Mitsunobu and M. Yamada, Bull. Chem. Soc. Jpn., 1967, 40, 2380.
19. Atomic coordinates, thermal parameters and bond lengths and angles have been deposited in the Cambridge Crystallographic Data Centre (CCDC). See Instructions for Authors, J. Chem. Soc., Perkin Trans. 1, 1997, Issue 1. Any request to the CCDC for this material should quote the full literature citation and the reference number 207/89.
20. M. Hoffmann, Synthesis, 1986, 557.
21. E. Vedejs, D. A. Engler and J. E. Telschow, J. Org. Chem., 1978, 43, 188.
22. C. Prakash, S. Saleh and I. A. Blair, Tetrahedron Lett., 1989, 30, 19.