【正文】 s, 1H, ArH), (s, 1H, NH2), (s, 2H, ArH), (s, 1H, NH2), (s, 1H, NH), ~ (m, 2H), (m, 2H), (m, 1H), (m, 1H), (s, 3H), ~ (m, 2H), (m, 1H), (m, 2H), ~ (m, 1H), ~ (m, 3H), (s, 3H), (s, 6H). 13C NMR (126 MHz, DMSO) δ (C=S), (C=O), (C=N), , , , , , , , , , , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3457, 3299, 2958, 2926, 2866, 1718, 1651, 1490, 1283, 1103, 1081, 556. ESIMS (+), m/z: [M + H]+ . HRMS (EI) calcd for C23H34N4OS (M+): , found .乙酰脫氫樅胺7異煙酰腙 (3e)：淡黃色固體，產(chǎn)率： 65%. ~ ℃. 1H NMR (500 MHz, CDCl3) δ (s, 1H, NNHC=O), (s, 2H, PyH), (m, 3H, PyH, ArH), (s, ArH), (s, 1H, NH), ~ (m, 1H), (m, 1H), (m, 1H), (m, 2H), (s, 2H), (s, 3H), ~ (m, 2H), ~ (m, 3H), ~ (m, 9H), (s, 3H). 13C NMR (126 MHz, CDCl3) δ (COCH3), (NHCO), (C=N), (PyC), (PyC), (C9), (C13), (PyC), (C12), (C8), (C14), (C11), (PyC), (PyC), , , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3424, 2959, 2921, 2868, 1736, 1656, 1527, 1382, 1283, 1140. ESIMS (+), m/z: [M + H]+. HRMS (EI) calcd for C28H36N4O2 (M+): , found .三氟乙酰脫氫樅胺7氨基脲酰腙 (3f)：白色粉末， 產(chǎn)率：78%. ~ ℃. 1H NMR (500 MHz, CDCl3) δ (s, 1H, NNHC=S), (s, 1H, ArH), (s, 2H, ArH), (s, 1H, NH), (m, 2H, NH2), ~ (m, 3H), (m, Hz, 1H), (m, 1H), (m, 2H), ~ (m, 3H), ~ (m, 8H), (m, 6H). 13C NMR (126 MHz, CDCl3) δ (COCF3), (CONH2), (C9), (C13), (C12), (C8), (C14), (C11), (CF3), , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3500, 3450, 3377, 1961, 2929, 2870, 1724, 1689, 1670, 1569, 1421, 1121, 1155. ESIMS (+), m/z: [M + H]+, [M + Na]+. HRMS (EI) calcd for C23H31F3N4O2 (M+): , found .三氟乙酰脫氫樅胺7異煙酰腙 (3g)：淡黃色粉末，產(chǎn)率：74%. ~ ℃. 1H NMR (500 MHz, CDCl3) δ (s, 1H, NNHC=O), (s, 2H, PyH), (s, 2H, PyH), (s, 1H, ArH), (s, 2H, ArH), (s, 1H, NH), (m, 2H), ~ (m, 1H), ~ (m, 1H), (m, 1H), (s, 2H), (m, 1H), (s, 1H), (s, 1H), (m, 1H), (s, 1H), (m, 6H), (s, 3H), (s, 3H). 13C NMR (126 MHz, CDCl3) δ (NHCO), (COCF3), (PyC), (PyC), (C9), (C13), (C=N), (PyC), (C12), (C8), (C14), (C11), (PyC), (PyC), (CF3), , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3424, 3255, 1961, 2927, 2870, 1720, 1660, 1385, 1208, 1152. ESIMS(+), m/z: [M + H]+ ,[M + Na]+. HRMS (EI) calcd for C28H33F3N4O2 (M+): , found .新型脫氫樅胺衍生物的合成及其生物活性研究23 化合物 3h~3i 的合成將 10 mmol 2a 用 50 ml 乙醇溶解，加入 150 ml 四口瓶中，再加入 3 mmol 碳酰肼和少量醋酸，加熱回流 8 h。反應(yīng)結(jié)束后減壓蒸除溶劑，殘留物用硅膠柱層析[洗脫劑: V(石油醚)/V(乙醇 )=9/1]分離得到目標(biāo)產(chǎn)物 3h 和 3i。化合物 3h 產(chǎn)率 45%，化合物 3i 產(chǎn)率 25%。乙酰脫氫樅胺7碳酰腙 (3h)：黃色固體，產(chǎn)率：45%. ~ ℃. 1H NMR (300 MHz, CDCl3) δ (s, 1H, NNHC=O), (s, 1H, ArH), (s, 1H, NH2), (d, J = Hz, 1H, NH2), (m, 2H, ArH), (s, 1H, NHCO), (s, 1H, NH), (m, 3H), (d, J = Hz, 4H), (dd, J = , Hz, 4H), – (m, 3H), (d, J = Hz, 3H), (s, 3H), (s, 7H). 13C NMR (75 MHz, CDCl3) δ (NHCO), (NNHCO), (C=N), , , , , , , , , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3748, 3423, 3195, 2950, 2924, 2865, 1675, 1629, 1507, 1403, 1386. ESIMS(+), m/z: [M + H]+ ,[M + Na]+. 雙 (乙酰脫氫樅胺7 碳酰腙) (3i)：淡黃色固體，產(chǎn)率 25%. ~ ℃. 1H NMR (300 MHz, CDCl3) δ (m, 2H, NNHCO), (s, 2H, ArH), (s, 4H, ArH), (m, 2H, NHCO), – (m, 6H), – (m, 2H), (d, J = Hz, 2H), (t, J = Hz, 6H), – (m, 2H), (s, 4H), (s, 4H), – (m, 14H), (m, 14H). 13C NMR (75 MHz, CDCl3) δ (NHCO), (NNHCO), (C=N), , , , , , , , , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3425, 2959, 2926, 2867, 1641, 1420, 1386, 1123, 1058, 553. ESIMS(+), m/z: [M + H]+ . 脫氫樅胺肟類(lèi)衍生物的合成 合成路線(xiàn)NHR1NOR24EtOH,AcOHrefulx,5h2 4aR1=COH3R2=H4b1=32=C34cR1=COH3R2=H2Ar4d1=F32=圖 22 化合物 4a~3d 的合成路線(xiàn)Fig. 22 Synthetic route of pounds 4a~3d新型脫氫樅胺衍生物的合成及其生物活性研究24 化合物 4a~4d 的合成以化合物 4a 的合成為例。將 () 2a 溶于 80mL 乙醇，加入 250mL 四口瓶中，再加入 無(wú)水乙酸鈉和 ()鹽酸羥胺，攪拌使之充分混合。室溫下滴加 8g 氫氧化鈉于 50mL 水中的溶液，將 pH 調(diào)至 8。裝上冷凝管，加熱回流 1h，趁熱將反應(yīng)液倒入 300mL 冰水中，析出大量白色固體 4a，靜置 10mim，濾出固體。將固體產(chǎn)物干燥后用二氯甲烷溶解，用硅膠柱層析[洗脫劑: V(石油醚)/V(乙酸乙酯)=1/1]分離得到目標(biāo)產(chǎn)物 4a。用相同的方法合成出 4b、4c、4d 。乙酰脫氫樅胺7肟 (4a)：黃色固體，產(chǎn)率：78%. . ~ ℃. 1H NMR (500 MHz, CDCl3) δ (s, 1H, ArH), (s, 2H, ArH), (s, 1H, NH), ~ (s, 3H, OCH3), (m, Hz, 1H), (m Hz, 1H), ~ (m, 1H), (m Hz, 1H), (m 1H), (m 3H), (m, 2H), (m 2H), ~ (m, 9H), ~ (m, 6H). 13C NMR (126 MHz, CDCl3) δ (C=O), (C=N), (C9), (C13), (C12), (C8), (C14), (C11), (OCH3), , , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3302, 2959, 2930, 2869, 1721, 1651, 1460, 1378, 1052, 889, 755. ESIMS (+), m/z: [M + H]+, [M + Na]+. HRMS (EI) calcd for C23H34N2O2 (M+): , found .乙酰脫氫樅胺7(O甲基肟) (4b)：白色固體，產(chǎn)率：85%. . ~ ℃. 1H NMR (500 MHz, CDCl3) δ (s, 1H, ArH), (s, 2H, ArH), (s, 1H, NH), ~ (s, 3H, OCH3), (m, Hz, 1H), (m Hz, 1H), ~ (m, 1H), (m Hz, 1H), (m 1H), (m 3H), (m, 2H), (m 2H), ~ (m, 9H), ~ (m, 6H). 13C NMR (126 MHz, CDCl3) δ (C=O), (C=N), (C9), (C13), (C12), (C8), (C14), (C11), (OCH3), , , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3302, 2959, 2930, 2869, 1721, 1651, 1460, 1378, 1052, 889, 755. ESIMS (+), m/z: [M + H]+, [M + Na]+. HRMS (EI) calcd for C23H34N2O2 (M+): , found .乙酰脫氫樅胺7(O芐基肟) (4c)：淡黃色粘稠液體 ，產(chǎn)率：87%. . ~℃. 1H NMR (500 MHz, CDCl3) δ (s, 1H, ArH), (s, 2H, ArH), (s, Hz, 2H, ArH), ~ (m, 1H, ArH), (m, 2H, ArH), (s, 1H, NH), (s, 2H, NOCH2), (m, Hz, 1H), ~ (m, 3H), (m, Hz, 1H), (s, 3H), ~ (m, 2H), (m, 2H), ~ (m, 1H), ~ (m, 8H), (s, 3H), (s, 3H). 13C NMR (126 MHz, CDCl3) δ (C=O), (C=N), , , , , , , , , , , , , (NOCH2), , , , , , , , , , , , , , , . IR (KBr, ν/cm?1): 3304, 2958, 2927, 2868, 1737, 1652, 1558, 1456, 1367, 1287, 1018, 940, 739. ESIMS (+), m/z: [M + H]+. HRMS (EI) calcd for C29H38N2O2 (M+): , found .三氟乙酰脫氫樅胺7肟 (4d)：淡黃色固體，產(chǎn)率：65%. ~ ℃. 1H 新型脫氫樅胺衍生物的合成及其生物活性研究25NMR (500 MHz, CDCl3) δ (s, 1H, ArH), ~ (m, 2H, ArH), (s, 1H, NH), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), (s, 1H), (s, 1H), (m, 7H), (s, 3H), ~ (m, 3H). 13C NMR (126 MH