Analogues of oxytocin with an oxime bridge using chemoselectively addressable building blocks

Tetrahedron Letters

Volumn 37, Issue 38, 1996, Pages 6861-6864

  Wahl, Franck ^a   Mutter, Manfred ^a  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

OXYTOCIN DERIVATIVE;

ARTICLE; DRUG DESIGN; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MOLECULAR MODEL; PEPTIDE SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0030590456     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01537-7     Document Type: Article

References (13)

1. Analogues Franck Wahl and Manfred Mutter * Institute of Organic Chemistry, University of Lausanne, BCH-Dorigny, CH-1015 Lausanne, Switzerland
2. 1. Osapay, G.; Melacini, G.; Zhu, Q.; Tehrani, L.; Goodman, M. Lett. Pept. Sci. 1994, 1, 81-87.
3. 2. (a) Spinella, M.J.; Malik, A.B.; Everitt, J.; Andersen, T.T. Proc. Natl. Acad. Sci. USA 1991, 88, 7443-7446.
4. (b) Smith, C.W.; Walter, R.; Moore, S.; Makofske, R.C.; Meienhofer, J. J. Med. Chem. 1978, 21, 117-120.
5. 3. (a) Jost, K.; Prochazka, Z.; Cort, J.H.; Barth, T.; Skopkova, J.; Prusik, Z.; Sorm, F., R. Coll. Czech. Chem. Commun. 1974, 39, 2835-2856.
6. (b) Nutt, R.F.; Veber, D.F.; Saperstein, R. J. Am. Chem. Soc. 1980, 102, 6539-6545.
7. 4. (a) Dawson, P.E.; Kent, S.B.H. J. Am. Chem. Soc. 1993, 115, 7263.
8. (b) Vilaseca, L.A.; Rose, K.; Werlen, R.; Meunier, A.; Offord, C.L.; Nichols, C.L.; Scott, W.L. Bioconjugate Chem. 1993, 4, 515.
9. (c) Pallin, T.D.; Tam, J.P. J. Chem. Soc., Chem. Commun. 1995, 2021-2022.
10. (d) Tuchscherer, G. Tetrahedron Lett. 1993, 34, 8419-8422.
11. 5. Wood, S.P.; Tickle, I.J.; Treharne, A.M.; Pitts, J.E.; Mascarenhas, Y.; Li, J.Y.; Husain, J.; Cooper, S.; Blundell, T.L.; Hruby, V.J.; Buku, A.; Fischman, A.J.; Wyssbrod, H.R. Science 1986, 232, 633-636.
12. 6. Abbreviations: Aoa, aminooxy acetic acid; DAP, 2,3-diaminopropionic acid; DCM, dichloromethane; DMF, N,N, dimethylformamide; Fmoc, 9-fluorenylmethyloxycarbonyl; OSu, O-succinimide ester; PyBOP, benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate; SPPS, Solid Phase Peptide Synthesis.
13. 7. Triethylamine (4 equiv.) was added slowly to a cooled suspension of commercially available O-(carboxymethyl)hydroxylamine and trityl bromide (2 equiv.) in DCM/DMF (2:1). Then it was heated to reflux for 2h under argon. After cooling the solvents were evaporated and the residue extracted with ethyl acetate, washed with water, brine and dried over magnesium sulfate. N-Trityl aminooxy acetic acid was recrystallised in ethyl acetate to give 77% of pure white crystals. Of which the OSu ester was prepared by addition of N-hydroxysuccinimide (1 equiv.) and dicyclohexylcarbodiimide (1 equiv.) in dioxane/ethyl acetate (2:1) and stirred overnight at 4°C. After filtration and evaporation, the solid residue was recrystallised in isopropanol to give the N-Trityl-aminooxyacetic acid hydroxysuccinimide ester (Trt-Aoa-OSu) in 72% yield. Fmoc-Dap-OH was refluxed in dichloromethane in the presence of trimethylsilyl chloride (2 equiv.) for 2 h 30 min, then after cooling, diisopropylethylamine (2 equiv.) and N-Trityl-aminooxyacetic acid hydroxysuccinimide ester (Trt-Aoa-OSu) were added slowly at room temperature and stirred for 6h. Methanol was added to quench the reaction, the solvents evaporated and the residue extracted with DCM, washed with 10% aq. citric acid, brine and dried over magnesium sulphate. The product was purified by silica gel flash chromatography with DCM/methanol to give 1 as a white solid (80% yield).