Potent thrombin inhibitors via a 20-membered ring olefin metathesis macrocyclization

Tetrahedron Letters

Volumn 44, Issue 11, 2003, Pages 2401-2404

  Nantermet, Philippe G ^a   Selnick, Harold G ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKENE; THROMBIN INHIBITOR;

ARTICLE; CHEMICAL REACTION; CYCLIZATION; DRUG POTENCY; DRUG SYNTHESIS; GRUBBS OLEFIN METATHESIS; HYDROLYSIS; METHODOLOGY;

EID: 0037430548     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00216-8     Document Type: Article

References (20)

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7. Unpublished results from our laboratories. Also see: US Patent, US 6,180,627 B1, issued Jan. 30, 2001.
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14. Horwell D.C., Hugues J., Hunter J.C., Pritchard M.C., Richardson R.S., Roberts E., Woodruff G.N. J. Med. Chem. 34:1991;404-414.
15. Obtained from the alkylation of the corresponding phenol. US Patent, US 5,792,779, issued Jun. 8, 1998.
16. Bis(tricyclohexylphosphine)benzylidine ruthenium(IV) dichloride, 20 mol%, 0.002 M.
17. 5: 572.1462, found 572.1469.
18. Compounds 13 and 14 were isolated in a 1:1 ratio. It should, however, be possible to alter this ratio and perhaps eliminate the formation of 14 by modifying the reaction parameters such as the nature of the catalyst (rhodium for example) and reaction time.
19. d=-15.4° (c 0.21, MeOH).
20. Full details to be published elsewhere in due time.