反应详情

Tripeptide 4 (0.308 g, 0.62 mmol) was dissolved in methanol (30 cm3). The reaction flask was flushed with nitrogen and 10 wt. % palladium on activated carbon (66 mg, 0.062 mmol) was added and the mixture was hydrogenated at 1 atmosphere of hydrogen. After 30 min a white solid precipitated. Water (15 cm3) was added to dissolve the solid and the reaction was stirred for 18 h. The reaction was filtered through Celite™ washed with methanol/water and the solvent removed to yield an oil which was contaminated with palladium. The filtration was repeated again and the solvent removed to yield a white sold which was suspended in methanol and placed in a freezer overnight. The solid was filtered, washed with ice-cold methanol and dried to yield GPNorval (0.142 g, 84%) as white flakes. GPNorval was shown to be a 78:22 trans:cis mixture of conformers by 13C NMR analysis (the ratio was estimated from the integration of the Proβ-C carbons at δ 29.4 and 31.6 and the Proγ-C carbons at δ 24.1 and 21.9 of the major and minor conformers respectively): [α]D −79 (c 0.1 in water); δH (300 MHz; D2O) 0.85 (3H, d, J 7.4, Eγ-CH3), 1.29 (2H, sextet, J 7.0, Eγ-H2), 1.53-1.75 (2H, m, Eβ-H2) 1.88-2.05 (3H, m, Proβ-HAHB, Proγ-H2) 2.09-2.27 (1H, m, Proβ-HAHB), 3.51-3.82 (4H, m, Proδ-H2, Glyα-H2), 4.09 (0.78H, dd, J 7.8 5.0, Eα-H), 4.14* (0.22H, dd, J 9 5.0, Eα-H) and 4.41 (1H, m, Proα-H); δC (75 MHz; D2O) 12.8* (CH3, Eγ-CH3), 12.9 (CH3, Eγ-CH3), 18.5 (CH2, Eγ-C), 18.7* (CH2, Eγ-C), 21.9* (CH2, Proγ-C), 24.1 (CH2, Proγ-C), 29.4, (CH2, Proβ-C), 31.6* (CH2, Proβ-C), 33.3* (CH2, Eβ-C), 33.8 (CH2, Eβ-C), 40.6 (CH2, Glyα-C), 46.8 (CH, Proδ-C), 47.5* (CH, Proδ-C), 55.1 (CH, Eα-C), 60.0* (CH, Proα-C), 60.4 (CH, Proα-C), 166.6 (quat., Gly-CO), 173.1 (quat., Pro-CON), 178.9* (quat., Eα-CO) and 179.0 (quat., Eα-CO); m/z (FAB+) 272.1641 (MH+.C12H22N3O4 requires 272.1610).

1. additionwas added
2. customAfter 30 min a white solid precipitated
3. additionWater (15 cm3) was added
4. dissolutionto dissolve the solid
5. filtrationThe reaction was filtered through Celite™
6. washwashed with methanol/water
7. customthe solvent removed
8. customto yield an oil which
9. filtrationThe filtration
10. customthe solvent removed
11. customto yield
12. waitplaced in a freezer overnight
13. filtrationThe solid was filtered
14. washwashed with ice-cold methanol
15. customdried
16. customto yield GPNorval (0.142 g, 84%) as white flakes
17. additioncis mixture of conformers by 13C NMR analysis (the ratio