Novel and general method for the preparation of peptidyl argininals

Tetrahedron Letters

Volumn 37, Issue 24, 1996, Pages 4109-4112

  Tamura, Susan Y ^a   Semple, J Edward ^a   Ardecky, Robert J ^a   Leon, Pamela ^a   Carpenter, Steven H ^a   Ge, Yu ^a   Shamblin, Brian M ^a   Weinhouse, Michael I ^a   Ripka, William C ^a   Nutt, Ruth F ^a  

^a Dendreon   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE DERIVATIVE; N(G) NITROARGININE; PEPTIDE; THROMBIN INHIBITOR;

ARTICLE; DRUG SYNTHESIS; ENANTIOMER; PROTEIN STRUCTURE;

EID: 0029972959     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00777-0     Document Type: Article

References (14)

1. Scarborough, R.M.; Annual Reports in Medicinal Chemistry, Bristol, J.A.; ed. 1995, 30, 71.
2. Bajusz, S.; Szell, E.; Bagdy, D.; Garabas, E.; Horvath, G.; Dioszegi, M.; Fittler, Z.; Szabo, G.; Juhasz, A.; Tomori, E.; Szilagyi, G. J. Med. Chem. 1990, 33, 1729.
3. (a) McConnell, R.M.; Barnes, G.E.; Hoyng, C.F.; Gunn, J.M. J. Med. Chem. 1990, 33, 86.
4. (b) Murphy, A.M.; Dagnino, R., Jr.; Vallar, P.V.; Trippe, A.J.; Sherman, S.L.; Lumpkin, R.H.; Tamura, S. Y.; Webb, T.R. J. Am. Chem. Soc. 1992, 114, 3156.
5. (a) Rote, W.E.; Dempsey, E.M.; Oldeshulte, G.L.; Ardecky, R.J.; Tamura, S.Y.; Nutt, R.F.; Bergum, P.W.; Tran, H.S.; Anderson, S.M.; Vlasuk, G.P. Circulation, 1994, 90, 1344.
6. (b) Richard, B.M.; Nolan, T.G.; Tran, H.S.; Miller, M.M.; Nutt, R.F.; Vlasuk, G.P. American Heart Association 67th Scientific Session, Dallas, Texas, 1994; poster 968.
7. Vlasuk, G.P.; Webb, T.R.; Pearson, D.A., Abelman, M.M. US Patent #5,999,999 (1994).
8. (a) Fehrentz, J.-A.; Castro, B. Synthesis 1983, 676.
9. (b) Goel, O.P.; Krolls, U.; Stier, M.; Kesten; S. Organic Syntheses 1988, 67, 69.
10. 4a NMR and HPLC analyses indicate that 2 exists as a mixture of the two cyclic hemiaminal forms and the free aldehyde.
11. Details on the NMR structure determination will be reported in due course.
12. 3OD) δ 1.30 (2 overlapping t, 3H, Et), 1.43-1.85 (m, Boc+Arg β, γ) + 2.11 (tt, J=13.7, 4.5Hz, total 13H, Arg β, γ), 3.12 (t, J=12Hz, Arg δ) + 3.24 (dt, J=13.2, 2.6Hz, total 1H, Arg δ), 3.55-3.59 (m, 3H, Arg δ+Et), 3.70-3.82 (m, 1H, αCH),5.71 (brs) + 5.61 (brs, total 1H, anomeric CH).
13. 3OD) δ 1.30 (t, J= 7.0Hz, 3H), 1.67-2.05 (m, 4H), 3.26 (dt, J=13.4Hz, 2.8Hz, 1H), 3.55-3.41 (m, 1H), 3,55-3.70 (m, 2H), 3.72-3.79 (m, 1H), 5.95 (d, J=3.3Hz) + 6.05 (d, J=3.3Hz, total 1H).
14. The methyl ester is hydrolyzed in minute quantities (<3%) under these conditions.