反应详情

trans-4-Hydroxy-L-proline 1 (0.28 g, 2.13 mmol) and sodium hydrogen carbonate (0.18 g, 2.13 mmol) were dissolved in water (3 cm3) at room temperature. N-benzyloxycarbonyl-glycyl-N-hydroxysuccinimide 2 (0.44 g, 1.44 mmol) in dimethoxyethane (3 cm3) was added dropwise over a period of 5 min. The solution was stirred for 2.5 then acidified with conc. hydrochloric acid (38%) to pH 1. The solution was placed in a refrigerator overnight. Ethyl acetate (2×20 cmr3) was added and the resulting organic layers dried (MgSO4), filtered and evaporated under reduced pressure to yield a light pinky foam, which was purified by flash column chromatography (10% methanol/methylene chloride) to produce acid 3 (0.32 g, 70%) as a clear foam. Acid 3 was shown to be an 77:23 trans:cis mixture of conformers by 1H NMR analysis (the ratio was estimated from the integration of the signals at (δ 4.33-4.38 and 4.52-4.54, assigned to the Proα-H of the major and minor conformers respectively): [α]D −75.5 (c 0.08 in MeOH); OH (300 MHz; CD3OD) 1.89-1.94 (0.77H, m, Proβ-HAHB), 2.08-2.14 (1H, m, Proβ-HAHB), 2.14-2.16* (0.23H, m, Proβ-HAHB), 3.17-3.20 (1H, m, Proδ-HAHB), 3.53-3.57 (1H, m, Proδ-HAHB), 3.73-3.78 (1H, d, J 17.1, Glyα-HAHB), 3.87-3.93 (1H, d, J 17.1, Glyα-HAHB), 4.20-4.30* (0.23H, m, Proγ-H), 4.33-4.38 (1.54H, m, Proγ-H and Proα-H), 4.52-4.54* (0.23H, t, J 7.0, Proα-H) 4.94 (2H, s, OCH2Ph) and 7.11-7.23 (5H, m, Ph); δC (75 MHz, CD3OD) 39.0 (CH2, Proβ-C), 41.3* (CH2, Pro-C), 44.2* (CH2, Proδ-C), 44.8 (CH2, Proδ-C), 55.9 (CH2, Glyα-C), 56.2* (CH2, Glyα-C), 59.5* (CH, Proα-C), 60.1 (CH, Proα-C), 68.5 (CH2, OCH2Ph), 68.7* (CH2, OCH2Ph), 69.7* (CH, Proγ-C), 71.7 (CH, Proγ-C), 129.6 (CH, Ph), 129.7 (CH, Ph), 130.2 (CH, Ph), 138.9 (quat., Ph), 159.6 (quat., NCO2), 170.1 (quat., Gly-CO), 171.6* (quat., Gly-CO), 175.9* (quat., CO2H) and 176.3 (quat., CO2H),; m/z (FAB+) 323.1240 (M+.C16H20N2O5 requires 320.1243).

1. customwas placed in a refrigerator overnight
2. dry with materialthe resulting organic layers dried (MgSO4)
3. filtrationfiltered
4. customevaporated under reduced pressure
5. customto yield a light pinky foam, which
6. customwas purified by flash column chromatography (10% methanol/methylene chloride)