Stereoselective synthesis of C-6 hydroxy tricyclic sulfone as a γ-secretase inhibitor

Tetrahedron Letters

Volumn 52, Issue 26, 2011, Pages 3382-3385

  Su, Jing ^a   Tang, Haiqun ^a   McKittrick, Brian A ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

cis Ring opening of an epoxide; Regioselective; Stereoselective; Suzuki coupling

Indexed keywords

EPOXIDE; GAMMA SECRETASE INHIBITOR; HYDROXY TRICYCLIC SULFONE; SULFONE; UNCLASSIFIED DRUG;

ARTICLE; CIS ISOMER; DRUG DETERMINATION; DRUG SYNTHESIS; STEREOCHEMISTRY; SUZUKI REACTION;

EID: 79957585478     PISSN: 00404039     EISSN: 18733581     Source Type: Journal    
DOI: 10.1016/j.tetlet.2011.04.091     Document Type: Article

References (18)

1. R. Xu, D. Cole, T. Asberom, T. Bara, C. Bennett, D.A. Burnett, J. Clader, M. Domalski, W.J. Greenlee, L. Hyde, H. Josien, H. Li, M. McBriar, B.A. McKittrick, A.T. McPhail, D. Pissarnitski, L. Qiang, M. Rajagopalan, T. Sasikumar, J. Su, H. Tang, W.-L. Wu, L. Zhang, and Z. Zhao Bioorg. Med. Chem. Lett. 20 2010 2591
2. Su, J.; Tang, H.; McKittrick, B. A.; Xu, R.; Clader, J. W.; Greenlee, W. J.; Hyde, L.; Zhang, L. Bioorg. Med. Chem. Lett. Accepted for publication. http://dx.doi.org/10.1016/j.bmcl.2011.03.094.
3. O. Wallace, K. Lauwers, J. Dodge, S. May, J. Calvin, R. Hinklin, H. Bryant, P. Shetler, M. Adrian, A. Geiser, M. Sato, and T. Burris J. Med. Chem. 49 2006 843
4. M. Majewski, and J. MacKinnon Can. J. Chem. 72 1994 1699
5. P. Selles, and U. Mueller Org. Lett. 6 2004 277
6. G.T. Crisp, and A.G. Meyer J. Org. Chem. 57 1992 6972
7. T. Biftu, G. Scapin, S. Singh, D. Feng, J.W. Becker, G. Eiermann, H. He, K. Lyons, S. Patel, A. Petrov, R. Sinha-Roy, B. Zhang, J. Wu, X. Zhang, G.A. Doss, N.A. Thornberry, and A.E. Weber Bioorg. Med. Chem. Lett. 17 2007 3384
8. 3 in a 500 mL RB flask needs to be stirred at around 1100 rpm with a 1 × 5/16″ stirring bar (Fisher brand). Scales larger than that would require a mechanic stirrer.
9. J.S. Yadav, B.V.S. Reddy, and G. Baishya Chem. Lett. 2002 906
10. The olefin product 12 was presumed to be formed via a cationic intermediate. J. Li, and C. Li Tetrahedron Lett. 42 2001 793
11. A.E. Vougioukas, and H.B. Kagan Tetrahedron Lett. 28 1987 6065
12. We are only interested in the cis isomer since the membrane Aβ40 assay results in Ref. [2] indicated that the cis isomer was at least 20-fold more active than the trans isomer.
13. 17
14. M.G. Constantino, V. Lacerda Jr., and V. Aragao Molecules 6 2001 770
15. M. Pineschi, F. Bertolini, R.M. Haak, P. Crotti, and F. Macchia Chem. Commun. 400 2005 1426
16. Y. Kubota, K. Haraguchi, M. Kunikata, M. Hayashi, M. Ohkawa, and H. Tanaka J. Org. Chem. 71 2006 1099
17. F. Badali, A. Karalis, W.Y. Tham, and J.M. White Aust. J. Chem. 49 1996 1293
18. 2 atmosphere at room temperature for 16 h and diluted with 400 mL EtOAc followed by washing with water (100 mL × 2), brine (50 mL × 1). The organic was concentrated and the residue was purified by flash chromatography (35% EtOAc/hexane) to yield exclusively the cis adduct 11a (5.8 g, 74% yield).