Enzymatic kinetic resolution of piperidine atropisomers: Synthesis of a key intermediate of the farnesyl protein transferase inhibitor, SCH66336

Journal of Organic Chemistry

Volumn 65, Issue 18, 2000, Pages 5451-5459

  Morgan, Brian ^a   Zaks, Aleksey ^a   Dodds, David R ^a,c   Liu, Jinchu ^a   Jain, Rama ^a   Megati, Sreeni ^a   Njoroge, F George ^b   Girijavallabhan, Viyyoor M ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Dept of Chem Res and Tum Biology ^*  (United States)

^c BRISTOL MYERS SQUIBB COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATE; LONAFARNIB; LORATADINE; PIPERIDINE DERIVATIVE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAS PROTEIN; SOLVENT; TRIACYLGLYCEROL LIPASE;

ACYLATION; ARTICLE; CATALYSIS; CHIRALITY; ENANTIOMER; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME KINETICS; NONHUMAN; PSEUDOMONAS;

ACYLATION; ALKYL AND ARYL TRANSFERASES; ENZYME INHIBITORS; KINETICS; PIPERIDINES; PYRIDINES; SPECTRUM ANALYSIS; STEREOISOMERISM;

EID: 0033828991     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo991513v     Document Type: Article

References (49)

1. (a) Barbacid, M. Annu. Rev. Biochem. 1987, 56, 779-827.
2. (b) Bos, J. L. Cancer Res. 1989, 49, 4682-4689.
3. (c) Lowy, D. R.; Willumsen, B. M. Annu. Rev. Biochem. 1993, 62, 851-891.
4. Casey, P. J.; Solski, P. A.; Der, C. J.; Buss, J. E. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 8323-8327.
5. Levitzki, A. Eur. J. Biochem. 1994, 226, 1-13.
6. Njoroge, F. G.; Taveras, A. G.; Kelly, J.; Remiszewski, S.; Mallams, A. K.; Wolin, R.; Afonso, A.; Cooper, A. B.; Rane, D. F.; Liu, Y.-T.; Wong, J.; Vibulbhan, B.; Pinto, P.; Deskus, J.; Alvarez, C. S.; del Rosario, J.; Connolly, M.; Wang, J.; Desai, J.; Rossman, R. R.; Bishop, W. R.; Patton, R.; Wang, L.; Kirschmeier, P.; Bryant, M. S.; Nomeir, A. A.; Lin, C.-C.; Liu, M.; McPhail, A. T.; Doll, R. J.; Girijavallabhan, V. M.; Ganguly, A. K. J. Med. Chem. 1998, 41, 4890-4902.
7. Villani, F. J.; Magatti, C. V.; Vashi, D. B.; Wong, J.; Popper, T. L. Arzneim-Forsch./Drug Res. 1986, 36, 1311-1314.
8. Complete details of the reduction of (±)-5 will be presented elsewhere: Njoroge et al., manuscript in preparation.
9. Since this behavior results from rotation about two bonds instead of one, it is not atropisomerism as strictly defined. Nevertheless, the more familiar term will be used: Oki, M. Topics in Stereochemistry; John Wiley and Sons: New York, 1983; Vol. 14, pp 1-81.
10. Conformational diastereomers due to restricted piperidinylidene ring flipping have been described in similar tricyclic systems: Piwinski, J. J.; Wong, J. K.; Chan, T.-M.; Green, M. J.; Ganguly, A. K. J. Org. Chem. 1990, 55, 3341-3350.
11. (a) Faber, K., Biotransformations in Organic Chemistry, 3rd ed.; Springer-Verlag: Berlin, 1997.
12. (b) Drauz, K.; Waldmann, H., Eds. Enzyme Catalysis in Organic Synthesis: A Comprehensive Handbook; VCH Publishers: New York, 1995.
13. (c) Wong C.-H.; Whitesides, G. Enzymes in Synthetic Organic Chemistry; Pergamon: New York, 1994.
14. (d) Poppe, L.; Novak, L. Selective Biocatalysis; VCH Publishers: New York, 1992.
15. (e) Kazlauskas, R. J.; Bornscheuer, U. T. Biotechnology, Vol. 8a: Biotransformations 1, 2nd ed.; Kelly, D. R., Ed.; Wiley-VCH: Weinheim, Germany, 1998; pp 37-191.
16. (f) Preparative Biotransformations: Whole Cell and Isolated Enzymes in Organic Synthesis; Roberts S. M.; Wiggins, K.; Casy, G., Phythian, S., Eds.; Wiley: Chichester, U.K., 1992.
17. (g). Biotransformations CD-ROM; Chapman and Hall, Electronic Publishing Division: London, U.K.
18. (h) BioCatalysis; Synopsis Scientific Systems Ltd: Leeds, U.K.
19. (a) Zaks, A.; Dodds, D. R. Drug Discovery Today 1997, 2, 513-531.
20. (b) Patel, R. N. Adv. Appl. Microbiol. 1997, 43, 91-140.
21. (c) Sheldon, R. A. Enzymatic Reactions in Organic Media; Koskinen, A. M. P., Klibanov, A. M., Eds.; Blackie Academic and Professional: Glasgow, U.K. 1996; pp 266-307.
22. (a) Fortier, G.; Mackenzie, S. L. Biotechnol. Lett. 1986, 8, 777-782.
23. (b) Nakajima, H.; Kitabatake, S.; Tsurutani, R.; Yamamoto, K.; Tomioka, I.; Imahori, K. Int. J. Pept. Protein Res. 1986, 28, 179.
24. (c) Asensio, G.; Andreu, C.; Marco, J. A. Tetrahedron Lett. 1991, 32, 4197-4198.
25. (d) Gutman, A. L.; Meyer, E.; Yue, X.; Abell, C. Tetrahedron Lett. 1992, 33, 3943-3946.
26. (e) Paradkar, V. M.; Dordick, J. S. J. Am. Chem. Soc. 1994, 116, 5009-5010.
27. (f) Chen, S. Y.; Kao, C. L.; Wang, K. T. Biorg. Med. Chem. Lett. 1994, 4, 443-448.
28. (g) Herradon, B.; Valverde, S. Synlett 1995, 599-602.
29. (h) Orsat, B.; Alper, P. B.; Moree, W.; Mak, C.-P.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 712-713.
30. (i) Takayama, S.; Lee, S. T.; Hung, S.-C.; Wong, C.-H. Chem. Commun. 1999, 127-128.
31. Chen, C.-S.; Fujimoto, Y.; Girdaukas, G.; Sih, C. J. J. Am. Chem. Soc. 1982, 104, 7294-7299.
32. The moderate selectivity of TFEOBOC suggested the enzymatic introduction of the Cbz group followed by catalytic hydrogenation to remove the Cbz group and reduce the olefin to yield (R)-(+)-5 directly. However transfer hydrogenation of (±)-4 with cyclohexane/10% Pd/C in refluxing EtOH resulted in complete removal of the 3-Br substituent, with the olefin remaining intact.
33. Increasing the size of the acylating agent from vinyl acetate to isobutyric anhydride resulted in a dramatic increase in the selectivity of a Novozyme 435 catalyzed desymmetrization of a prochiral 1,3-diol. See: (a) Nielsen, C. M.; Sudhakar, A. U.S. Patent 5,756,830, 1998. (b) Morgan, B.; Dodds, D. R.; Zaks, A.; Andrews, D. R.; Klesse, R. J. Org. Chem. 1997, 62, 7736-7743.
34. Increasing the size of the acylating agent from vinyl acetate to isobutyric anhydride resulted in a dramatic increase in the selectivity of a Novozyme 435 catalyzed desymmetrization of a prochiral 1,3-diol. See: (a) Nielsen, C. M.; Sudhakar, A. U.S. Patent 5,756,830, 1998. (b) Morgan, B.; Dodds, D. R.; Zaks, A.; Andrews, D. R.; Klesse, R. J. Org. Chem. 1997, 62, 7736-7743.
35. Toyobo LIP-300 is a lipoprotein lipase (P. aeruginosa) immobilized on Hyflo Supercel. The commercial catalyst contains ∼1% enzyme. See: Nakatani, T.; Hiratake, J.; Yoshikawa, K.; Nishioka, T.; Oda, J. Biosci. Biotech. Biochem. 1992, 56, 1118-1123.
36. Vinyl isobutyrate resulted in decomposition of starting material, whereas acetone oxime isobutyrate and isobutyric anhydride showed little or no selectivity at low temperature.
37. Sawa is a supplier of the Toyobo enzymes. LIP-300 and LIP-301 are the same enzyme; the different designations are for different pricing schedules.
38. Zaks, A.; Klibanov, A. M. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 3192-3196.
39. Halling, P. J. Biotech. Tech. 1992, 6, 271-276. Hogberg, H.-E.; Edlund, H.; Berglund, P.; Hedenstrom, E. Tetrahedron: Asymm. 1993, 4, 2123-2126.
40. Halling, P. J. Biotech. Tech. 1992, 6, 271-276. Hogberg, H.-E.; Edlund, H.; Berglund, P.; Hedenstrom, E. Tetrahedron: Asymm. 1993, 4, 2123-2126.
41. Azeotropic distillation of the substrate solution in the presence of the enzyme resulted in ∼10% lowered conversion, but without diminution of enzyme selectivity.
42. For the effect of acids on the enantioselectivity of C. cylindracea catalyzed acylations with anhydride. See: Berger, B.; Rabiller, C. G.; Konigsberger, K.; Faber, K.; Griengl, H. Tetrahedron: Asymm. 1990, 1, 541-546.
43. At the concentrations shown in Figure 5, to produce 0.5 equiv of isobutyric acid by hydrolysis of TFEOiBu would require 486 ppm water.
44. (a) Rakels, J. L. L.; Straathof, A. J. J.; Heijnen, J. J. Tetrahedron: Asymm. 1994, 5, 93-100.
45. (b) Boaz, N. W.; Zimmerman, R. L. Tetrahedron: Asymm. 1994, 5, 153-156.
46. (c) Stead, P.; Marley, H.; Mahmoudian, M.; Webb, G.; Noble, D.; Ip, Y. T.; Piga, E.; Rossi, T.; Roberts, S.; Dawson, M. J. Tetrahedron: Asymm. 1996, 7, 2247-2250.
47. (d) Parker, M.; Brown, S. A.; Robertson, L.; Turner, N. J. Chem. Commun. 1998, 2247-2248.
48. A 5:1 solvent/(-)-4 mixture was maintained at reflux, or else heated to 240 °C over a period of 2.5 h, maintained at 240 °C for 2 h, then cooled, and subjected to a standard workup. Solvents (bp, °C) were Decalin (189-191), diethylbenzene (180-182), di(ethyleneglycol) dibutyl ether (256), heptamethylnonane (240), hexadecane (287), N-methylacetamide (204-206), phenyl ether (259).
49. Conditions: (±)-5, 5 mg; isopropenyl acetate, 10 equiv; EtOAc or TBME, 2 mL; room temperature; 250 rpm.