Oxetanyl Amino Acids for Peptidomimetics

Transcription

1 Oxetanyl Amino Acids for Peptidomimetics Guido P. Möller, Steffen Müller, Bernd T. Wolfstädter, Susanne Wolfrum, Dirk Schepmann, Bernhard Wünsch, Erick M. Carreira * 1 Additional Schemes General Information Oxetanyl Amines Imine Synthesis Alanine Analogue Determination of Absolute Configuration Leucine Analogue Determination of Absolute Configuration and Alternative Route Serine Analogue Determination of Absolute Configuration Aspartic Acid Analogue Determination of Absolute Configuration Phenylalanine Analogues Determination of Absolute Configuration Tyrosine Analogues Determination of Absolute Configuration Valine Analogue Proline Analogue Determination of Absolute Configuration Cysteine Analogue Determination of Absolute Configuration Glycine Analogue Triflates Dipeptide Building Blocks Leu-Enkephalin Analogues References

2 Figure 49 1 H- and 13 C-NMR Spectra of

3 Figure 50 1 H- and 13 C-NMR Spectra of

4 Figure 51 1 H- and 13 C-NMR Spectra of

5 Figure 52 1 H- and 13 C-NMR Spectra of

6 Figure 53 1 H- and 13 C-NMR Spectra of

7 Figure 54 1 H- and 13 C-NMR Spectra of

8 Figure 55 1 H- and 13 C-NMR Spectra of

9 Figure 56 1 H- and 13 C-NMR Spectra of

10 Figure 57 1 H- and 13 C-NMR Spectra of

11 Figure 58 1 H- and 13 C-NMR Spectra of

12 Figure 59 1 H- and 13 C-NMR Spectra of

13 Figure 60 1 H- and 13 C-NMR Spectra of

14 Figure 61 1 H- and 13 C-NMR Spectra of

15 Figure 62 1 H- and 13 C-NMR Spectra of the less polar diastereomer of

16 Figure 63 1 H- and 13 C-NMR Spectra of the more polar diastereomer of

17 Figure 64 1 H- and 13 C-NMR Spectra of

18 Figure 65 1 H- and 13 C-NMR Spectra of

19 Figure 66 1 H- and 13 C-NMR Spectra of

20 Figure 67 1 H- and 13 C-NMR Spectra of

21 Figure 68 1 H- and 13 C-NMR Spectra of

22 Figure 69 1 H- and 13 C-NMR Spectra of

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24 Figure 70 1 H-, 13 C- and 19 F-NMR Spectra of

25 174

26 Figure 71 1 H-, 13 C- and 19 F-NMR Spectra of

27 Figure 72 1 H- and 13 C-NMR Spectra of 1r. 176

28 Figure 73 1 H- and 13 C-NMR Spectra of 1d. 177

29 Figure 74 1 H- and 13 C-NMR Spectra of 1p. 178

30 Figure 75 1 H- and 13 C-NMR Spectra of 1q. 179

31 Figure 76 1 H- and 13 C-NMR Spectra of 1l. 180

32 Figure 77 1 H- and 13 C-NMR Spectra of epi-1l. 181

33 Figure 78 1 H- and 13 C-NMR Spectra of 1e. 182

34 Figure 79 1 H- and 13 C-NMR Spectra of 1f. 183

35 Figure 80 1 H- and 13 C-NMR Spectra of 1g. 184

36 Figure 81 1 H- and 13 C-NMR Spectra of 1a. 185

37 Figure 82 1 H- and 13 C-NMR Spectra of 1b. 186

38 Figure 83 1 H- and 13 C-NMR Spectra of 1c. 187

39 Figure 84 1 H- and 13 C-NMR Spectra of 1j. 188

40 Figure 85 1 H- and 13 C-NMR Spectra of 1h. 189

41 Figure 86 1 H- and 13 C-NMR Spectra of 1i. 190

42 Figure 87 1 H- and 13 C-NMR Spectra of 1k. 191

43 Figure 88 1 H- and 13 C-NMR Spectra of 1m. 192

44 Figure 89 1 H- and 13 C-NMR Spectra of 1n. 193

45 Figure 90 1 H- and 13 C-NMR Spectra of 1o. 194

46 Figure 91 1 H- and 13 C-NMR Spectra of epi-1s. 195

47 Figure 92 1 H- and 13 C-NMR Spectra of 1s. 196

48 Figure 93 1 H- and 13 C-NMR Spectra of 1t. 197

49 Figure 94 1 H- and 13 C-NMR Spectra of 2e. 198

50 199

51 Figure 95 COSY, HSQC, HMBC Spectra of 2e. 200

52 Figure 96 1 H- and 13 C-NMR Spectra of 2b. 201

53 202

54 Figure 97 COSY, HSQC, HMBC Spectra of 2c. 203

55 Figure 98 1 H- and 13 C-NMR Spectra of

56 Figure 99 1 H- and 13 C-NMR Spectra of

57 Figure H- and 13 C-NMR Spectra of 2d. 206

58 207

59 Figure 101 COSY, HSQC, HMBC Spectra of 2d. 208

60 Figure H- and 13 C-NMR Spectra of

61 Figure H- and 13 C-NMR Spectra of 2c. 210

62 211

63 Figure 104 COSY, HSQC, HMBC Spectra of 2c. 7 References 1. Antoni, P.; Hed, Y.; Nordberg, A.; Nyström, D.; von Holst, H.; Hult, A.; Malkoch, M. Angewandte Chemie International Edition 2009, 48, Huang, S.-X.; Powell, E.; Rajski, S. R.; Zhao, L.-X.; Jiang, C.-L.; Duan, Y.; Xu, W.; Shen, B. Organic Letters 2010, 12, Meseguer, B.; Alonso-Díaz, D.; Griebenow, N.; Herget, T.; Waldmann, H. Chemistry A European Journal 2000, 6, Feenstra, R. W.; Stokkingreef, E. H. M.; Nivard, R. J. F.; Ottenheijm, H. C. J. Tetrahedron 1988, 44, Studte, C.; Breit, B. Angewandte Chemie International Edition 2008, 47, Yajima, H.; Mizokami, N.; Kiso, M.; Jinnouchi, T.; Kai, Y.; Kiso, Y. Chemical & pharmaceutical bulletin 1974, 22, Kitamoto, T.; Marubayashi, S.; Yamazaki, T. Chemistry Letters 2006, 35, Hammadi, A.; Nuzillard, J. M.; Poulin, J. C.; Kagan, H. B. Tetrahedron: Asymmetry 1992, 3,

64 9. Elliott, R. L.; Marks, N.; Berg, M. J.; Portoghese, P. S. Journal of Medicinal Chemistry 1985, 28, Bradford, M. M. Analytical Biochemistry 1976, 72, Stoscheck, C. M. Methods in enzymology 1990, 182, Cheng, Y.; Prusoff, W. H. Biochemical pharmacology 1973, 22, Eddy, N. B.; Leimbach, D. The Journal of pharmacology and experimental therapeutics 1953, 107,