Efficient synthesis of an α-trifluoromethyl-α-tosyloxymethyl epoxide enabling stepwise double functionalisation to afford CF3-substituted tertiary alcohols

Tetrahedron Letters

Volumn 49, Issue 34, 2008, Pages 5101-5104

  Keeling, Steven P ^a   Campbell, Ian B ^a   Coe, Diane M ^a   Cooper, Tony W J ^a   Hardy, George W ^a   Jack, Torquil I ^a   Jones, Haydn T ^a   Needham, Deborah ^a   Shipley, Tracy J ^a   Skone, Philip A ^a   Sutton, Peter W ^a   Weingarten, Gordon A ^a   Macdonald, Simon J F ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Trifluoromethyl epoxide; Desymmetrisation; Doubly electrophilic; Glucocorticoid receptor agonists

Indexed keywords

ALCOHOL; ALPHA TRIFLUOROMETHYL ALPHA TOSYLOXYMETHYL EPOXIDE; ENZYME; EPOXIDE;

ARTICLE; CHIRALITY; ENANTIOMER; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; STEREOCHEMISTRY; SYNTHESIS;

EID: 46749137489     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2008.06.011     Document Type: Article

References (26)

1. Gelb M.H., Svaren J.P., and Abeles R.H. Biochemistry 24 (1985) 1813
2. Patel D.V., Rielly-Gauvin K., and Ryono D.E. Tetrahedron Lett. 29 (1988) 4665
3. Huguenot F., and Brigaud T. J. Org. Chem. 71 (2006) 7075
4. Wang H., Zhao X., Li Y., and Lu L. Org. Lett. 8 (2006) 1379
5. Ogu K., Matsumoto S., Akazome M., and Ogura K. Org. Lett. 7 (2005) 589
6. Sinisi R., Sani M., Candiani G., Parente R., Pecker F., Bellosta S., and Zanda M. Tetrahedron Lett. 46 (2005) 6515
7. Lauzon C., and Charette A.B. Org. Lett. 8 (2006) 2743
8. Schacke H., Schottelius A., Docke W.-D., Strehlke P., Jaroch S., Schmees N., Rehwinkel H., Hennekes H., and Asadullah K. Proc. Nat. Acad. Sci. 101 (2004) 227
9. Clackers M., Coe D.M., Demaine D.A., Hardy G.W., Humphreys D., Inglis G.G.A., Johnston M.J., Jones H.T., House D., Loiseau R., Minick D.J., Skone P.A., Uings I., McLay I.M., and Macdonald S.J.F. Bioorg. Med. Chem. Lett. 17 (2007) 4737 and references therein
10. Song J.J., Tan Z., Xu J., Reeves J.T., Yee N.K., Ramdas R., Gallou F., Kuzmich K., DeLattre L., Lee H., Feng X., and Senanayake C.H. J. Org. Chem. 72 (2007) 292
11. Mohler M.L., He Y., Wu Z., Hong S.-S., and Miller D.D. Expert Opin. Ther. Patents 17 (2007) 37 This paper provides a succinct review of the non-steroidal GR agonist area and contains many leading references
12. Barnett, H. A.; Campbell, I. B.; Coe, D. M.; Cooper, A. W. J.; Inglis, G. G. A.; Jones, H. T.; Keeling, S. P.; Macdonald, S. J. F.; McLay, I. M.; Skone, P. A.; Weingarten, G. G.; Woolven, J. M. PCT Int. Appl. 2008, WO2008000777. CAN 148:100602.
13. Barnett, H. A.; Campbell, I. B.; Coe, D. M.; Cooper, A. W. J.; Inglis, G. G. A.; Jones, H. T.; Keeling, S. P.; Macdonald, S. J. F.; McLay, I. M.; Skone, P. A.; Weingarten, G. G.; Woolven, J. M. PCT Int. Appl. 2007 WO2007144327. CAN 148:79023.
14. Bravo P., Farina A., Frigerio M., Meille S.V., Viani F., and Soloshonok V. Tetrahedron: Asymmetry 5 (1994) 987-1004
15. Ruppert I., Schlich K., and Volbach W. Tetrahedron Lett. 25 (1984) 2195
16. Lee T.W., Proudfoot J.R., and Thomson D.S. Bioorg. Med. Chem. Lett. 16 (2006) 654
17. Yamauchi Y., Katagiri T., and Uneyama K. Org. Lett. 4 (2002) 173
18. Griffith W.P., Ley S.V., Whitcombe G.P., and White A.D. J. Chem. Soc., Chem. Commun. (1987) 1625
19. Canney D.J., Lu H.-F., McKeon A.C., Yoon K.-W., Xu K., Holland K.D., Rothman S.M., Ferrendelli J.A., and Covey D.F. Bioorg. Med. Chem. 6 (1998) 43
20. Carbonate on polymer support supplied by Fluka (capacity ∼3.5 mmol/g).
21. Preparative separation of the enantiomers of 1. Column Chiralpak AD, 2 inch × 20 cm eluting with heptane/ethanol 98:2 with a flow rate of 75 mL/min. 1 b elutes at around 17 min and 1a at around 21 min. Racemate loadings <200 mg are required to achieve acceptable separation of the enantiomers.
22. Analytical separation of the enantiomers of 9. Column Chiralcel OD-H, 25 cm, eluting with 5% ethanol in heptane with a flow rate of 1 mL/min. The enantiomers appear at 8.61 and 9.98 min. The material processed to 9a from 1a is composed of 5% of the first eluting enantiomer and 95% of the second eluting enantiomer.
23. Using Alphamerix Screening Kits 1 and 2 (Mann Associates) hits were obtained from C. rugosa lipase (AE02), Achromobacter spp. lipase (AE04), Alcaligenes spp. lipase (AE05), Burkholderia cepacia lipase P1 (AE06), Pseudomonas stutzeri lipase (AE07), Burkholderia cepacia lipase P2 (AE012) and Mucor javanicus lipase (AE013).
24. 31P NMR signals do not overlap. The authentic diester was inert to Mosher's ester derivatisation. All enzyme hits preferentially produced the same enantiomer.
25. Parallel screening for diacetate or dibutyrate hydrolysis activity also gave a number of hits, all of which resulted in complete hydrolysis to the triol under a variety of conditions.
26. Sepabeads EC-EP is a porous epoxy-resin support produced by Resindion-Mitzubishi.