卜俊文,段文貴,林桂汕,何 云,姚 池,岑 波

(廣西大學(xué) 化學(xué)化工學(xué)院，廣西 南寧 530004)

樟腦是一種具有雙環(huán)單萜結(jié)構(gòu)的非木質(zhì)林產(chǎn)品，天然存在于樟科植物中，是我國的可再生天然優(yōu)勢生物質(zhì)資源，也可由α-蒎烯經(jīng)多步反應(yīng)合成之。樟腦及其衍生物具有廣泛的生物活性，如強(qiáng)心[1]、止痛[2-3]、止咳[4-5]、抗菌[6-8]、除草[9]、抗病毒[10]、驅(qū)蟲殺蟲[11-14]等，在醫(yī)藥和農(nóng)藥等領(lǐng)域有著廣泛的應(yīng)用。

此外，含有喹喔啉骨架的化合物顯示多種生物活性，如殺菌[15-16]、殺蟲[17]、抗病毒[18-19]、抗腫瘤[20-21]、除草[22-24]、降血糖[25]、抑制膽固醇酯轉(zhuǎn)移蛋白酶[26]等。喹喔啉骨架是重要的有機(jī)合成單元并廣泛存在于天然產(chǎn)物、醫(yī)藥及農(nóng)藥分子中。

基于近年來本課題組對松香松節(jié)油基生物活性化合物的研究成果[27-32]，利用活性基團(tuán)拼接原理，通過氧化、縮合等反應(yīng)將喹喔啉骨架與D-(+)-樟腦骨架相結(jié)合，合成得到一系列樟腦基喹喔啉類化合物(3a～3s，Scheme 1)。利用UV-Vis,1H NMR,13C NMR,FT-IR及HR-MS(ESI)等進(jìn)行表征，并測試了目標(biāo)化合物的抑菌活性以及除草活性。

Scheme 1

1 實(shí)驗(yàn)部分

1.1 儀器與試劑

MP420型全自動熔點(diǎn)儀；SHIMADZU UV-1800型紫外光譜儀；Nicolet iS 50 FT-IR型紅外光譜儀；AVANCE Ⅲ HD型600 MHz超導(dǎo)核磁共振儀(CDCl3為溶劑，TMS為內(nèi)標(biāo))；TSQ Quantum Access MAX型液相色譜-質(zhì)譜聯(lián)用儀；Waters 1525型高效液相色譜儀。

D-(+)-樟腦(AR,GC純度96.0%)，上海晶純試劑有限公司；3,6-二溴-1,2-苯二胺參照文獻(xiàn)[33]自制；D-(+)-樟腦醌(2)參照文獻(xiàn)[34]合成。其余所用試劑均為分析純。

1.2 合成

(1)3a～3r的合成(以3a為例)

將0.50 g(3 mmol)D-(+)-樟腦醌、10 mL乙腈、5滴三氟乙酸和0.34(3 mmol)鄰苯二胺混合，80 ℃攪拌1～4 h(TLC監(jiān)測)。除去溶劑，殘?jiān)苡?0 mL乙酸乙酯中，分別用飽和碳酸鈉溶液(3×5 mL)和去離子水(3×5 mL)洗滌，無水硫酸鈉干燥后，經(jīng)硅膠柱層析[洗脫劑：V(石油醚)/V(乙酸乙酯)=5/1]純化得白色固體3a。

用類似方法合成3b～3r。

樟腦基喹喔啉(3a)：白色固體，收率83%，m.p.75.6～76.3 ℃；UV-Vis(EtOH)λmax:314.50,241.00 nm;1H NMR(600 MHz,CDCl3)δ:8.08～8.01(m,1H,5-H or 8-H),8.01～7.96,(m,1H,5-H or 8-H),7.67～7.61(m,2H,6,7-H),3.06(d,J=4.5 Hz,1H,12-H),2.36～2.25(m,1H,13-Hexo),2.13～2.00(m,1H,14-Hendo),1.46～1.39(m,5H,13-Hendo,14-Hexo,18-H),1.12(s,3H,16-H),0.63(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:165.52,163.75,141.51,141.31,128.78,128.65,128.07,128.05,54.21,53.79,53.29,31.84,24.63,20.29,18.52,10.04;IR(KBr)ν:3059,2957,2926,2869,1510,1471,1444 cm-1;MS(ESI)m/z:238.12{[M+H]+}。

樟腦基6,7-二甲基喹喔啉(3b)：淡黃色固體，收率82%，m.p.77.1～79.0 ℃;UV-Vis(EtOH)λmax:336.96,322.00,247.00 nm;1H NMR(600 MHz,CDCl3)δ:7.80(s,1H,5-H or 8-H),7.72(s,1H,5-H or 8-H),3.02(d,J=4.4 Hz,1H,12-H),2.45(s,6H,Ar-CH3),2.31～2.22(m,1H,13-Hexo),2.08～1.99(m,1H,14-Hendo),1.43～1.36(m,5H,13-Hendo,14-Hexo,18-H),1.10(s,3H,16-H),0.61(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:164.56,162.82,140.07,139.91,137.91,137.90,128.30,128.13,54.18,53.64,53.26,31.91,24.70,20.23,20.08,20.04,18.55,10.06;IR(KBr)ν:3044,2959,2922,2873,1606,1504,1451 cm-1;MS(ESI)m/z:267.11 {[M+H]+}。

樟腦基6,7-二氟喹喔啉(3c)：白色固體，收率86%，m.p.158.2～159.1 ℃；UV-Vis(EtOH)λmax:312.50,240.50 nm;1H NMR(600 MHz,CDCl3)δ:7.82～7.76(m,1H,5-H or 8-H),7.76～7.70(m,1H,5-H or 8-H),3.05(d,J=4.5 Hz,1H,12-H),2.35～2.27(m,1H,13-Hexo),2.12～2.02(m,1H,14-Hendo),1.44～1.36(m,5H,13-Hendo,14-Hexo,18-H),1.12(s,3H,16-H),0.61(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:165.87,164.09,151.63,149.95,138.39,138.18,115.03,114.80,54.41,53.85,53.18,31.71,24.52,20.23,18.46,9.92;IR(KBr)ν:3089,3028,2983,2961,2924,2879,1612,1587,1528,1471 cm-1;MS(ESI)m/z:274.06{[M+H]+}。

樟腦基6,7-二氯喹喔啉(3d)：淡紅色固體，收率88%，m.p.144.0～147.0 ℃；UV-Vis(EtOH)λmax:322.50,247.00 nm;1H NMR(600 MHz,CDCl3)δ:8.33(s,1H,5-H or 8-H),8.26(s,1H,5-H or 8-H),3.05(d,J=4.5 Hz,1H,12-H),2.35～2.26(m,1H,13-Hexo),2.12～2.02(m,1H,14-Hendo),1.42～1.37(m,5H,13-Hendo,14-Hexo,18-H),1.12(s,3H,16-H),0.61(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:166.83,165.03,140.93,140.77,132.98,132.80,124.04,124.03,54.15,53.96,53.24,31.64,24.45,20.27,18.41,9.88;IR(KBr)ν:3091,3055,2961,2928,2869,1585,1573,1475,1461 cm-1;MS(ESI)m/z:306.00 {[M+H]+}。

樟腦基6,7-二溴喹喔啉(3e):淡紅色固體，收率90%,m.p.138.5～140.2 ℃;UV-Vis(EtOH)λmax:336.25,324.00,250.00 nm;1H NMR(600 MHz,CDCl3)δ:8.15(s,1H,5-H or 8-H),8.08(s,1H,5-H or 8-H),3.06(d,J=4.5 Hz,1H,12-H),2.35～2.30(m,1H,13-Hexo),2.13～2.04(m,1H,14-Hendo),1.44～1.39(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.62(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:166.74,164.95,140.36,140.19,132.17,132.16,129.61,129.42,54.18,53.94,53.23,31.67,24.48,20.27,18.4,9.89;IR(KBr)ν:3077,2959,2930,2873,1579,1469,1457 cm-1;MS(ESI)m/z:395.87{[M+H]+}。

樟腦基6-氟喹喔啉(3f)：白色固體，收率38%,m.p.153.8～155.6 ℃;UV-Vis(EtOH)λmax:315.50,241.00 nm;1H NMR(600 MHz,CDCl3)δ:7.97(dd,J=9.1 Hz,5.8 Hz,1H,8-H),7.69(dd,J=9.5 Hz,2.8 Hz,1H,5-H),7.41(td,J=8.6 Hz,2.8 Hz,1H,7-H),3.06(d,J=4.4 Hz,1H,12-H),2.35～2.26(m,1H,13-Hexo),2.12～2.02(m,1H,14-Hendo),1.46～1.38(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.63(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:166.40,163.19,161.73,142.30,138.21,130.21,117.41,113.07,54.29,53.89,53.14,31.78,24.58,20.27,18.49,9.96;IR(KBr)ν:3053,2957,2930,2875,1632,1597,1514,1457 cm-1;MS(ESI)m/z:256.08{[M+H]+}。

樟腦基7-氟喹喔啉(3g)：白色固體，收率40%，m.p.153.2～154.4 ℃;UV-Vis(EtOH)λmax:314.50,241.00 nm;1H NMR(600 MHz,CDCl3)δ:8.01(dd,J=9.1 Hz,5.8 Hz,1H,5-H),7.62(dd,J=9.4 Hz,2.8 Hz,1H,8-H),7.40(td,J=8.6 Hz,2.8 Hz,1H,6-H),3.06(d,J=4.4 Hz,1H,12-H),2.36～2.26(m,1H,13-Hexo),2.12～2.01(m,1H,14-Hendo),1.45～1.37(m,5H,13-Hendo,14-Hexo,18-H),1.12(s,3H,16-H),0.62(s,3H,17-H);13C NMR (151 MHz,CDCl3)δ:164.98,164.65,161.73,142.10,138.44,130.38,117.40,112.92,54.30,53.71,53.31,31.78,24.59,20.28,18.49,9.99;IR(KBr)ν:2987,2961,2932,2869,1618,1561,1479,1440 cm-1;MS(ESI)m/z:256.09{[M+H]+}。

樟腦基6-氯喹喔啉(3h)：白色固體，收率37%，m.p.140.6～143.8 ℃;UV-Vis(EtOH)λmax:319.50,244.00 nm;1H NMR(600 MHz,CDCl3)δ:8.04(d,J=2.3 Hz,1H,5-H),7.91(d,J=8.8 Hz,1H,8-H),7.59(dd,J=8.8 Hz,2.3 Hz,1H,7-H),3.06(d,J=4.4 Hz,1H,12-H),2.36～2.26(m,1H,13-Hexo),2.14～2.02(m,1H,14-Hendo),1.44～1.38(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.63(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:166.47,164.01,141.96,139.83,133.59,129.74,128.77,128.0,54.25,53.90,53.22,31.75,24.54,20.28,18.47,9.94;IR(KBr)ν:3067,3046,2995,2955,2924,2867,1585,1473,1448 cm-1;MS(ESI)m/z:272.05{[M+H]+}。

樟腦基7-氯喹喔啉(3i)：白色固體，收率41%，m.p.139.8～142.8 ℃;UV-Vis(EtOH)λmax:315.50,241.00 nm;1H NMR(600 MHz,CDCl3)δ:7.99～7.94(m,2H,5,8-H),7.60(dd,J=8.8 Hz,2.3 Hz,1H,6-H),3.07(d,J=4.4 Hz,1H,12-H),2.35～2.3(m,1H,13-Hexo),2.1～2.01(m,1H,14-Hendo),1.49～1.36(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.63(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:165.80,164.70,141.79,140.04,133.59,129.90,128.76,127.85,54.24,53.82,53.28,31.74,24.55,20.28,18.47,9.97;IR(KBr)ν:3051,2961,2926,2875,1593,1508,1473,1448 cm-1;MS(ESI)m/z:272.05{[M+H]+}。

樟腦基6-溴喹喔啉(3j)：白色固體，收率39%，m.p.134.3～136.8 ℃;UV-Vis(EtOH)λmax:319.50,245.00 nm;1H NMR(600 MHz,CDCl3)δ:8.22(d,J=2.2 Hz,1H,5-H),7.85(d,J=8.8 Hz,1H,8-H),7.72(dd,J=8.8 Hz,2.2 Hz,1H,7-H),3.06(d,J=4.5 Hz,1H,12-H),2.34～2.27(m,1H,13-Hexo),2.11～2.04(m,1H,14-Hendo),1.44～1.39(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.62(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:166.43,164.13,142.28,140.14,131.41,131.31,129.93,121.58,54.24,53.91,53.27,31.76,24.51,20.28,18.47,9.93;IR(KBr)ν:3061,3038,2951,2920,2883,2869,1585,1504,1473,1453 cm-1;MS(ESI)m/z:316.98{[M+H]+}。

樟腦基7-溴喹喔啉(3k)：白色固體，收率40%，m.p.133.4～135.2 ℃；UV-Vis(EtOH)λmax:319.50,245.00 nm;1H NMR(600 MHz,CDCl3)δ:8.15(d,J=2.2 Hz,1H,8-H),7.90(d,J=8.8 Hz,1H,5-H),7.73(dd,J=8.8 Hz,2.2 Hz,1H,6-H),3.07(d,J=4.5 Hz,1H,12-H),2.36～2.28(m,1H,13-Hexo),2.12～2.03(m,1H,14-Hendo),1.44～1.38(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.63(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:165.91,164.65,142.10,140.34,131.40,131.12,130.08,121.57,54.2,53.86,53.26,31.70,24.55,20.27,18.46,9.96;IR(KBr)ν:3063,2959,2930,2875,1587,1500,1469,1451 cm-1;MS(ESI)m/z:316.98{[M+H]+}。

樟腦基6-硝基喹喔啉(3l)：白色固體，收率38%;m.p.154.8～156.7 ℃；UV-Vis(EtOH) λmax:297.00,257.00 nm;1H NMR(600 MHz,CDCl3)δ:8.88(d,J=2.5 Hz,1H,8-H),8.44(dd,J=9.0 Hz,2.5 Hz,1H,7-H),8.15(d,J=9.0 Hz,1H,5-H),3.14(d,J=4.5 Hz,1H,12-H),2.41～2.33(m,1H,13-Hexo),2.17～2.09(m,1H,14-Hendo),1.48～1.42(m,5H,13-Hendo,14-Hexo,18-H),1.17(s,3H,16-H),0.65(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:169.01,166.12,146.66,144.75,140.50,130.08,124.96,121.83,54.31,54.30,53.20,31.63,24.4,20.35,18.40,9.87;IR(KBr)ν:3089,2965,2926,2876,1606,1540,1504,1477,1448 cm-1;MS(ESI)m/z:283.07{[M+H]+}。

樟腦基7-硝基喹喔啉(3m)：白色固體，收率42%;m.p.154.6～156.3 ℃；UV-Vis(EtOH)λmax:297.00,256.50 nm;1H NMR(600 MHz,CDCl3)δ:8.95(d,J=2.5 Hz,1H,5-H),8.43(dd,J=9.0 Hz,2.5 Hz,1H,6-H),8.10(d,J=9.0 Hz,1H,8-H),3.13(d,J=4.5 Hz,1H,12-H),2.40～2.34(m,1H,13-Hexo),2.17～2.09(m,1H,14-Hendo),1.47～1.42(m,5H,13-Hendo,14-Hexo,18-H),1.17(s,3H,16-H),0.65(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:167.93,167.18,146.67,144.57,140.66,129.94,125.11,121.86,54.33,54.08,53.47,31.59,24.42,20.35,18.40,9.87;IR(KBr)ν:3110,3063,2965,2928,2873,1600,1540,1504,1448 cm-1;MS(ESI)m/z:283.07{[M+H]+}。

樟腦基5-甲基喹喔啉(3n)：淡黃色固體，收率42%，m.p.133.6～135.3 ℃；UV-Vis(EtOH)λmax:317.50,245.50 nm;1H NMR(600 MHz,CDCl3)δ:7.90(dd,J=8.1 Hz,0.6 Hz,1 H,8-H),7.53(t,J=7.6 Hz,1 H,7-H),7.51～7.47(m,1 H,6-H),3.12(d,J=4.4 Hz,1H,12-H),2.80(s,3H,Ar-CH3),2.34～2.26(m,1H,13-Hexo),2.09～2.04(m,1H,14-Hendo),1.46～1.39(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.64(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:164.94,162.61,141.53,140.38,136.72,128.56,127.52,126.76,54.19,53.65,53.35,31.80,24.85,20.32,18.59,17.70,10.06;IR(KBr)ν:3065,3028,2965,2926,2877,1591,1512,1479,1451 cm-1;MS(ESI)m/z:252.11{[M+H]+}。

樟腦基8-甲基喹喔啉(3o)：淡黃色固體，收率46%，m.p.132.3～134.2 ℃；UV-Vis(EtOH)λmax:317.00,245.50 nm;1H NMR(600 MHz,CDCl3)δ:7.83(d,J=7.3 Hz,1H,5-H),7.55～7.51(m,1H,6-H),7.50(d,J=7.1 Hz,1H,7-H),3.06(d,J=4.5 Hz,1H,12-H),2.81(s,3H,Ar-CH3),2.34～2.27(m,1H,13-Hexo),2.09～2.03(m,1H,14-Hendo),1.45～1.39(m,5H,13-Hendo,14-Hexo,18-H),1.13(s,3H,16-H),0.63(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:164.11,163.13,141.20,140.54,137.17,128.40,127.50,126.44,54.26,53.83,53.25,31.96,24.72,20.31,18.5,17.25,9.97;IR(KBr)ν:3063,3024,2967,2928,2879,1587,1516,1479 cm-1;MS(ESI)m/z:252.11{[M+H]+}。

樟腦基6-苯甲?；高?3p)：淡黃色固體，收率36%，m.p.105.1～106.9 ℃；UV-Vis(EtOH)λmax:322.50,258.00 nm;1H NMR(600 MHz,CDCl3)δ:8.37(d,J=0.9 Hz,1H,8-H),8.17～8.12(m,2H,5-H and 7-H),7.87(d,J=7.1 Hz,2H,COPh-H),7.62(t,J=7.5 Hz,1H,COPh-H),7.51(t,J=7.7 Hz,2H,COPh-H),3.08(d,J=4.4 Hz,1H,12-H),2.38～2.29(m,1H,13-Hexo),2.12～2.07(m,1H,14-Hendo),1.47～1.42(m,5H,13-Hendo,14-Hexo,18-H),1.14(s,3H,16-H),0.65(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:195.93,167.62,164.92,143.79,140.43,137.44,136.75,132.58,131.88,130.10,129.21,128.42,128.38,54.29,54.12,53.27,31.77,24.54,20.34,18.47,9.97;IR(KBr)ν:3059,2959,2926,2871,1661,1628,1600,1577,1451 cm-1;MS(ESI)m/z:342.08{[M+H]+}。

樟腦基7-苯甲?；高?3q)：淡黃色固體，收率40%，m.p.104.6～106.5 ℃；UV-Vis(EtOH)λmax:322.50,258.00 nm;1H NMR(600 MHz,CDCl3)δ:8.43(d,J=1.8 Hz,1H,8-H),8.15(dd,J=8.5 Hz,1.9 Hz,1H,6-H),8.10(d,J=8.5 Hz,1H,5-H),7.88(d,J=7.0 Hz,2H,COPh-H),7.63(t,J=7.5 Hz,1H,COPh-H),7.52(t,J=7.7 Hz,2H,COPh-H),3.12(d,J=4.5 Hz,1H,12-H),2.40～2.3(m,1H,13-Hexo),2.15～2.06(m,1H,14-Hendo),1.51～1.41(m,5H,13-Hendo,14-Hexo,8-H),1.15(s,3H,16-H),0.66(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:196.07,166.71,165.81,143.59,140.63,137.55,136.85,132.55,131.90,130.06,129.08,128.45,128.40,54.28,53.92,53.45,31.74,24.55,20.33,18.46,9.96;IR(KBr)ν:3059,2965,2930, 2873,1663,1632,1602,1579,1446 cm-1;MS(ESI)m/z:342.08{[M+H]+}。

樟腦基5,8-二溴喹喔啉(3r):白色固體，收率88%，m.p.203.5～206.1 ℃;UV-Vis(EtOH)λmax:319.50,256.00 nm;1H NMR(600 MHz,CDCl3)δ:7.84～7.81(m,2H,6,7-H),3.27(d,J=4.5 Hz,1H,12-H),2.39～2.31(m,1H,13-Hexo),2.12～2.09(m,1H,14-Hendo),1.49(s,3H,18-H),1.48～1.43(m,2H,13-Hendo,14-Hexo),1.16(s,3H,16-H),0.63(s,3H,17-H);13C NMR(151 MHz,CDCl3)δ:167.13,165.39,140.43,140.26,131.79,131.77,123.76,123.06,54.52,54.07,53.08,31.64,24.63,20.50,18.47,9.94;IR(KBr)ν:2955,2928,2871,1573,1477,1451 cm-1;MS(ESI)m/z:395.87{[M+H]+}。

(2)3s的合成

將0.50 g(1.7 mmol)3r、0.38 g(4.25 mmol) CuCN、5 mL DMF和0.3 mg KI混合，150 ℃攪拌3 h(TLC監(jiān)測)。反應(yīng)結(jié)束后倒入100 mL三氯化鐵水溶液中攪拌1 h，用乙酸乙酯萃取(3×5 mL)，有機(jī)相分別用飽和氯化鈉溶液(3×5 mL)和去離子水(3×5 mL)洗滌，無水硫酸鈉干燥后，經(jīng)硅膠柱層[洗脫劑：V(石油醚)/V(乙酸乙酯)=5/1]純化得淡綠色固體3s。

樟腦基5,8-二氰基喹喔啉(3s)：淡綠色固體，收率56%，m.p.236.9～238.5 ℃;UV-Vis(EtOH)λmax:322.50,247.00 nm;1H NMR(600 MHz,CDCl3)δ:8.07(s,2H,6,7-H),3.28(d,J=4.5 Hz,1H,12-H),2.42～2.38(m,1H,13-Hexo),2.21～2.11(m,1H,14-Hendo),1.48(s,3H,18-H),1.47～1.41(m,2H,13-Hendo,14-Hexo),1.17(s,3H,16-H),0.63(s,3H,17-H);13C NMR (151 MHz,CDCl3)δ:169.77,167.92,141.77,141.73,132.40,132.34,117.11,116.80,115.57,115.39,54.73,54.57,53.25,31.44,24.34,20.49,18.37,9.72;IR(KBr)ν:3073,2967,2934,2881,2236,1591,1477,1393 cm-1;MS(ESI)m/z:288.06{[M+H]+}。

(3) 目標(biāo)產(chǎn)物的生物活性測試

參考文獻(xiàn)[35]，本文采用離體法(也稱瓊脂稀釋法)測試目標(biāo)化合物的抑菌活性，結(jié)果列于表1；采用油菜平皿法和稗草小杯法測試目標(biāo)化合物的除草活性，結(jié)果列于表2。

表1 化合物3a～3s的抑菌活性*Table 1 Antifungal activity of compounds 3a～3s

表2 化合物3a～3s的除草活性Table 2 Herbicidal activity of compounds 3a～3s

2 結(jié)果與討論

2.1 合成

目標(biāo)化合物3a～3s的合成過程中，樟腦醌與鄰苯二胺的聚合會降低產(chǎn)率。采用較多量的溶劑可以減少聚合，提高目標(biāo)化合物的產(chǎn)率。

2.2 表征

D-(+)-樟腦醌2與單取代鄰苯二胺縮合將會產(chǎn)生兩個異構(gòu)體。以化合物3h和3i為例，通過2D-NMR中的HMBC對異構(gòu)體進(jìn)行了結(jié)構(gòu)分析鑒別。

δ圖1 化合物3h和3i的13C NMR譜圖Figure 1 13C NMR spectra of compounds 3h and 3i

結(jié)合HMBC(譜圖略)中的(a)與(b)均觀察到的18-H與C2相關(guān)；圖2(a)的HMBC中7-H與C11相關(guān)，不與C2相關(guān)，表明(a)為化合物3h；而圖2(b)的HMBC中6-H與C2相關(guān)，不與C11相關(guān)，表明(b)為化合物3i。此外，從圖1的13C NMR譜圖可知(a)的C2(166.47)化學(xué)位移大于(b)的C2(165.80)化學(xué)位移，(a)的C11(164.01)化學(xué)位移小于(b)的C11(164.70)化學(xué)位移。總之，5-位與6-位取代的樟腦基喹喔啉的C2化學(xué)位移大于7-位與8-位取代的樟腦基喹喔啉的C2化學(xué)位移，5-位與6-位取代的樟腦基喹喔啉的C11化學(xué)位移小于7-位與8-位取代的樟腦基喹喔啉的C11化學(xué)位移。上述結(jié)論與GLII報(bào)道的4個單取代甲基樟腦基喹喔啉的13C NMR數(shù)據(jù)相符[36]。從目標(biāo)產(chǎn)物的FT-IR數(shù)據(jù)可知，在3100～3000 cm-1出現(xiàn)的弱吸收峰為Ar—H的伸縮振動吸收峰；芳環(huán)骨架伸縮振動吸收峰出現(xiàn)在1600～1450 cm-1。這些HR-MS(ESI)數(shù)據(jù)均與目標(biāo)化合物3的分子量相符。

2.3 生物活性測試結(jié)果

(1) 抑菌活性

如表1的活性數(shù)據(jù)所示，在50 μg·mL-1的濃度下，絕大部分樟腦基喹喔啉化合物對花生褐斑病菌、小麥赤霉病菌、黃瓜枯萎病菌、蘋果輪紋病菌、番茄早疫病菌、玉米小斑病菌、西瓜炭疽病菌以及水稻紋枯病菌等8種病原菌有一定的抑制活性。從總體上看，目標(biāo)化合物對蘋果輪紋病菌、水稻紋枯病菌的抑制活性較好，其中化合物3a與3b對水稻紋枯病菌的抑制率分別為71.4%和70.1%(均達(dá)B級活性水平)；而化合物3r對蘋果輪紋病菌的抑制率達(dá)78.6%(B級活性水平)，優(yōu)于陽性對照百菌清。

(2) 除草活性

從表2可知，在100 μg·mL-1濃度下，目標(biāo)化合物對油菜胚根生長有一定的抑制作用。化合物3f和3g對油菜胚根生長的抑制率分別為75.8%和68.5%(均達(dá)B級活性水平)，均優(yōu)陽性對照于丙炔氟草胺。

以D-(+)-樟腦為原料，合成得到19個樟腦基喹喔啉化合物3a～3s。初步生物活性測試顯示，目標(biāo)化合物對8種植物病原菌具有一定的抑制活性?；衔?a與3b對水稻紋枯病菌的抑制率分別為71.4%和70.1%；化合物3r對蘋果輪紋病菌的抑制率達(dá)78.6%，優(yōu)于陽性對照百菌清。目標(biāo)化合物對油菜胚根生長具有一定的抑制作用，化合物3f與3g對油菜胚根生長的抑制率分別為75.8%和68.5%，均優(yōu)于陽性對照丙炔氟草胺。

致謝:抑菌和除草活性測試由南開大學(xué)元素有機(jī)化學(xué)國家重點(diǎn)實(shí)驗(yàn)室生物活性測試室完成，謹(jǐn)表謝意！