謝建武， 邵云霞， 張 雪， 吳佳順

(浙江師范大學 化學與生命科學學院,浙江 金華 321004)

靛紅衍生物，特別是螺靛紅衍生物，是一類具有特殊結(jié)構(gòu)的雜環(huán)化合物，具有很好的生物及藥物活性[1-2].靛紅中的3-羰基是一個很好的親電試劑，可以與其他親核試劑發(fā)生反應(yīng)從而構(gòu)造螺雜環(huán)化合物，若將3-羰基還原為3-羥基，那么可以作為親核試劑，與親電試劑發(fā)生串聯(lián)反應(yīng)，構(gòu)造成其他雜環(huán)化合物.因此，靛紅作為一個非常有用的合成中間體，被廣泛應(yīng)用在醫(yī)藥、農(nóng)藥、染料和精細化工等方面[3-5].螺環(huán)化合物是一類特殊的骨架，是一類兩平面互相垂直且具有特殊剛性結(jié)構(gòu)的化合物，廣泛存在于眾多的天然產(chǎn)物中.近年來，化學家們基于靛紅已經(jīng)合成了一系列具有生理活性的螺靛紅衍生物[6-7].

長期以來，本課題組一直專注于雜環(huán)化合物的合成，并取得了一系列的研究成果.以靛紅為原料，通過設(shè)計合成新底物，構(gòu)造新型的螺靛紅雜環(huán)化合物并取得了一定的進展，高選擇性地合成了一系列螺雜環(huán)化合物[8-12].基于已經(jīng)取得的一些成果，如果從靛紅出發(fā)，通過與丙二腈發(fā)生克腦文蓋爾縮合反應(yīng)(Knoevenagel condensation)，接著還原得到3-丙二腈基靛紅1a.底物1a在一定條件下與醛，如苯甲醛2a，發(fā)生羥醛縮合/環(huán)化/質(zhì)子遷移串聯(lián)反應(yīng)，就可以獲得新型的螺靛紅呋喃衍生物3aa，具體見圖1.

圖1 研究策略

1 實驗部分

1.1 試劑與儀器

WRS-1B 數(shù)字熔點儀(溫度計未經(jīng)校正)；Bruker Avance 400型或600型核磁共振波譜儀(DMSO或CDCl3為溶劑，TMS為基準物質(zhì))；有機反應(yīng)用薄層硅膠板(TLC)跟蹤監(jiān)測.德國Bruker高分辨質(zhì)譜儀(BioTOFⅢQ).

1.2 羥醛縮合/環(huán)化/質(zhì)子遷移串聯(lián)反應(yīng)的一般步驟

靛紅腈基底物1[13](0.20 mmol)、醛2(0.24 mmol)溶于1 mL二氯甲烷，接著加入三乙胺(0.04 mmol)，室溫攪拌6 h.經(jīng)快速柱層析(V(乙酸乙酯)/V(石油醚)=1/5)分離得到對應(yīng)的產(chǎn)物3或者4.

2 結(jié) 果

2.1 條件優(yōu)化

為了獲得該串聯(lián)反應(yīng)的優(yōu)化條件，以靛紅腈基底物1a及苯甲醛2a為反應(yīng)模板，對各種溶劑(氯仿、乙醇、甲苯、四氫呋喃和二氯甲烷)及堿(三乙胺、碳酸鉀和氫氧化鋰等)進行了篩選，發(fā)現(xiàn)該反應(yīng)在三乙胺的催化下，以二氯甲烷為溶劑，常溫下反應(yīng)6 h得到71%的產(chǎn)率及2∶1的非對映選擇性，相對于其他溶劑和堿，該條件為最好(見圖2).因此，羥醛縮合/環(huán)化/質(zhì)子遷移串聯(lián)反應(yīng)優(yōu)化條件為：靛紅腈基底物1及醛2在三乙胺的催化下，以二氯甲烷為溶劑，常溫下反應(yīng)6 h.根據(jù)此優(yōu)化條件，對底物的適用性進行了研究，實驗結(jié)果如表1所示.

圖2 羥醛縮合/環(huán)化/質(zhì)子遷移串聯(lián)反應(yīng)的優(yōu)化條件

2.2 底物擴展

獲得優(yōu)化該串聯(lián)反應(yīng)的優(yōu)化條件后，為了獲取更多的螺靛紅呋喃衍生物，隨后對有各種取代基靛紅衍生的腈基底物及芳香甲醛進行了適用性研究，實驗結(jié)果如圖3和表1所示.首先，靛紅腈基底物1a分別與不同取代基的芳香甲醛(2a—2i)進行反應(yīng)，以研究電子效應(yīng)對該串聯(lián)反應(yīng)的影響.芳香甲醛中芳環(huán)上的取代基的電子效應(yīng)對產(chǎn)物產(chǎn)率有非常大的影響.芳環(huán)上有拉電子基團，如氟(2b)、三氟甲基(2d)和氯(2h)等基團時，該串聯(lián)反應(yīng)順利進行，螺靛紅呋喃衍生物可以獲得70%以上的收率.特別是，當芳環(huán)上有三氟甲基強拉電子基團時，螺靛紅呋喃衍生物(3ad,3ad′)收率最高可達到91%.另外，所有的產(chǎn)物非對應(yīng)選擇性不是特別好，普遍為2∶1.不過，部分非對映異構(gòu)體可以很好地分離，如3ad和3ad′,3ae和3ae′,3ah和3ah′.此外，還對靛紅腈基底物進行了研究.靛紅腈基底物上的氮帶有其他取代基時，反應(yīng)活性較差，只有中等收率，非對映選擇性也僅有2∶1(3ba,3ca).

圖3 靛紅腈基底物1與芳香甲醛2發(fā)生串聯(lián)反應(yīng)的研究

編號1Ar23產(chǎn)率/%非對映選擇性a11aPh2a3aa712∶121ap-F-Ph2b3ab752∶131ap-CF3-Ph2d3ad463ad'45-41ap-Br-Ph2e3ae792∶151ap-Me-Ph2f3af402∶161ap-OMe-Ph2g3ag332∶171ap-Cl-Ph2h3ah373ah'39-81ao-Cl-Ph2i3ai722∶191bPh2a3ba472∶1101cPh2a3ca442∶1

注：a非對映選擇性測定通過核磁共振氫譜測定.

為了進一步研究該串聯(lián)反應(yīng)的適用性，對肉桂醛及其取代肉桂醛2′進行了研究和拓展，如圖4和表2所示.在優(yōu)化的條件下，該羥醛縮合/環(huán)化/質(zhì)子遷移串聯(lián)反應(yīng)都能夠順利進行，獲得了一系列螺靛紅呋喃衍生物.肉桂醛衍生的芳基上取代基的電子效應(yīng)對該反應(yīng)收率影響特別明顯.肉桂醛衍生物芳環(huán)上有拉電子基團時，產(chǎn)物螺靛紅呋喃衍生物可以獲得很好的收率，普遍在65%以上；若是肉桂醛衍生物芳環(huán)上有供電子基團時，則產(chǎn)率有所降低.特別值得注意的是，肉桂醛衍生物芳環(huán)上有拉電子基團，所得到2種螺靛紅衍生物的非對映異構(gòu)體可以在普通柱子上分離.此外，含有雜環(huán)的不飽和醛與靛紅腈基底物發(fā)生反應(yīng)，同樣可以獲得較好的收率，而且非對映選擇性最好，可以達到3∶1(4ae).

圖4 靛紅腈基底物1與α，β-不飽和醛2發(fā)生串聯(lián)反應(yīng)的研究

編號1Ar2'4產(chǎn)率/%非對映選擇性a11aPh2'a4aa631∶121ap-Cl-Ph2'c4ac652∶131aFuran-2-yl2'e4ae443∶141ap-NO2-Ph2'f4af324af'34-51ap-CF3-Ph2'g4ag374ag'31-61ap-OMe-Ph2'j4aj361∶171ap-Me-Ph2'k4ak532∶181bp-Br-Ph2'b4bb274bb'30-91cp-Br-Ph2'b4cb622∶1

注：a非對映選擇性測定通過核磁共振氫譜測定.

通過對產(chǎn)物3ae的單晶培養(yǎng)，確定了產(chǎn)物的相對構(gòu)型，見圖5.

圖5 單晶結(jié)構(gòu)圖

2.3 活性研究

為了研究該類化合物的抗菌活性，隨后采用速率生長法測試化合物對真菌的抑制活性.化合物3—4抑制黃瓜枯萎病菌(Fusariumoxysporum)，苦瓜枯萎病菌(Fusariumsemitectum)，番茄早疫病菌(Alternariasolani)，楊樹潰瘍病菌(Dothiorellagregaria)，小麥赤霉病菌(Fusariumgraminearum)和水稻稻瘟病菌(Magnaportheoryzae) 6種植物致病真菌菌絲生長活性如表3所示.結(jié)果表明，化合物4ac能很好地抑制供試菌番茄早疫病菌菌絲生長，而化合物4ag也能強烈抑制供試菌小麥赤霉病菌菌絲生長，其抑制率分別為65.0%，85.9%，與陽性對照藥放線菌酮(75.7%，100.0%)抑制效果相當.同時，根據(jù)表3中數(shù)據(jù)，發(fā)現(xiàn)在同一濃度下，不同化合物對同種植物致病真菌的抑制效果和同一化合物對不同植物致病真菌的抑制作用均不相同.但是，從整體上看，該類化合物對番茄早疫病菌和小麥赤霉病菌的抑制作用相對較好，而對其他4種植物致病真菌的抑制效果則較差，且部分化合物(如3af，3ba，4af和4ag)對個別植物致病真菌表現(xiàn)出微弱的抑制活性.以上結(jié)果再次表明，在螺環(huán)結(jié)構(gòu)中引入鹵素或者三氟甲基后，其抑菌效果會得到相應(yīng)的提高.

表3 部分化合物在50 mg/L下對真菌的抑制率 %

化合物黃瓜枯萎病菌苦瓜枯萎病菌番茄早疫病菌楊樹潰瘍病菌小麥赤霉病菌水稻稻瘟病菌3aa39.613.350.954.524.219.53ae35.042.814.542.361.840.43af<1.039.18.16.039.7<1.03ag<1.020.419.8<1.028.0<1.03ah11.610.412.444.236.95.93ai<1.014.99.959.632.035.33ba<1.04.67.631.566.4<1.03ca20.827.729.732.141.6<1.04aa8.24.720.9<1.053.0<1.04ac18.423.565.0<1.077.1<1.04ad<1.015.7<1.018.931.9<1.04ae<1.0<1.04.328.947.6<1.04af15.710.812.3<1.047.6<1.04ag27.037.240.516.385.9<1.04cb14.33.69.76.935.6<1.0亞胺環(huán)己酮100.068.175.7100.0100.0100.0

2.4 產(chǎn)物的表征數(shù)據(jù)：

1)3aa 淡黃色固體；熔點101～103 ℃;1H NMR(600 MHz;DMSO-d6)δ:10.59(s;1H),7.71(s,2H),7.21(t,J=7.3 Hz,2H),7.17(t,J=7.3 Hz,1H),7.03(d,J=7.3 Hz,2H),6.94～6.91(m,1H),6.69(d,J=7.7 Hz,1H),6.58(d,J=7.4 Hz,1H),5.82(s,1H).13C NMR (150 MHz,DMSO)δ:178.5,169.0,141.0,135.3,129.2,128.6,128.3,128.1,125.5,125.2,122.2,121.4,117.7,109.4,88.3,62.1;高分辨質(zhì)譜m/z：計算值C18H13N3NaO2+[M+Na+] 326.090 0,測量值326.091 6.

2)3ab 淡黃色固體；熔點 113～115 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.63(s,1H),7.76(s,2H),7.11～7.01(m,6H),6.71(d,J=7.5 Hz,1H),6.58(d,J=7.4 Hz,1H),5.84(s,1H).13C NMR(150 MHz,DMSO)δ:178.5(d,JC-F=246.4 Hz),169.0,162.6,160.9,141.2,131.7,128.8,128.1,127.9,127.6,125.8,121.6,117.8,115.2,115.0,109.6,87.7,62.1;高分辨質(zhì)譜m/z：計算值C18H12FN3NaO2+[M+Na+] 344.080 6,測量值344.081 6.

3)3ad 淡黃色固體；熔點 124～126 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.17(s,1H),7.84(s,2H),7.68(d,J=8.3 Hz,2H),7.63(d,J=7.3 Hz,1H),7.33～7.26(m,1H),7.21～7.07(m,3H),6.77(d,J=7.7 Hz,1H),6.03(s,1H).13C NMR(150 MHz,DMSO)δ:176.7,169.4,142.4,139.0,129.5,129.0(q,JC-F=31.6 Hz),128.8,128.7,128.3,126.2(q,JC-F=4.6 Hz),125.1,124.9,124.7,123.2(q,JC-F=266.3 Hz),122.4,117.8,109.7,88.4,61.9;高分辨質(zhì)譜m/z：計算值C19H12F3N3NaO2+[M+Na+] 394.077 4,測量值394.079 8.

4)3ad′ 淡黃色固體；熔點 124～126 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.69(s,1H),7.82(s,2H),7.61(d,J=8.1 Hz,2H),7.26(d,J=8.1 Hz,2H),7.09～6.98(m,1H),6.73(d,J=7.7 Hz,1H),6.67(t,J=7.5 Hz,1H),6.55(d,J=7.5 Hz,1H),5.96(s,1H).13C NMR(150 MHz,DMSO-d6)δ:178.2,168.8,141.1,140.1,128.9(q,JC-F=31.8 Hz),128.7,128.5,127.9,126.7,126.1,125.6(q,JC-F=6.1 Hz),125.1,124.9,123.1(q,JC-F=269.3 Hz),121.5,117.5,109.7,87.3,61.9;高分辨質(zhì)譜m/z：計算值C19H12F3N3NaO2+[M+Na+] 394.077 4,測量值394.079 8.

5)3ae 淡黃色固體；熔點 130～132 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.11(s,1H),7.77(s,2H),7.57(d,J=7.4 Hz,1H),7.47(d,J=8.5 Hz,2H),7.31～7.22(m,1H),7.11(t,J=7.9 Hz,1H),6.85(d,J=8.5 Hz,2H),6.74(d,J=7.7 Hz,1H),5.86(s,1H).13C NMR(150 MHz,DMSO-d6)δ:176.7,169.4,142.4,138.1,133.5,131.0,129.4,128.3,127.6,124.6,122.3,121.8,117.8,109.6,88.7,61.9;高分辨質(zhì)譜m/z：計算值C18H12BrN3NaO2+[M+Na+] 404.000 5,測量值404.003 1.

6)3af 淡黃色固體；熔點 112～114 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.59(s,1H),7.69(s,2H),7.07～6.99(m,4H),6.93(d,J=8.0 Hz,2H),6.70(d,J=7.7 Hz,2H),5.77(s,1H),2.18(s,3H).13C NMR(150 MHz,DMSO-d6)δ:178.1,168.6,142.1,140.6,137.1,131.8,128.8,128.3,128.1,125.2,124.9,121.1,117.4,109.1,88.2,61.8,20.3;高分辨質(zhì)譜m/z：計算值C19H15N3NaO2+[M+Na+] 340.105 6,測量值340.107 3.

7)3ag 淡黃色固體；熔點 119～121 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.56(s,1H),7.66(s,2H),7.26～7.15(m,1H),7.03～7.00(m,1H),6.97(d,J=8.6 Hz,2H),6.76(d,J= 8.8 Hz,2H),6.72～6.68(m,2H),5.74(d,J=5.0 Hz,1H),3.64(s,3H).13C NMR(150 MHz,DMSO-d6)δ:178.6,169.0,159.0,141.1,129.2,128.4,127.2,126.8,125.9,124.4,121.5,117.8,113.4,109.5,88.5,62.2,54.8;高分辨質(zhì)譜m/z：計算值C19H15N3NaO3+[M+Na+] 356.100 6,測量值356.101 7.

8)3ah 淡黃色固體；熔點 127～129 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.12(s,1H),7.78(s,2H),7.59(d,J=7.4 Hz,1H),7.45～7.32(m,2H),7.29～7.21(m,1H),7.18～7.07(m,1H),6.93(d,J=8.5 Hz,2H),6.75(d,J=7.7 Hz,1H),5.90(s,1H).13C NMR(150 MHz, DMSO-d6)δ:176.7,169.4,142.4,133.1,133.1,129.4,128.3,128.1,127.4,124.6,122.3,117.8,109.6,99.5,88.7,61.9;高分辨質(zhì)譜m/z：計算值C18H12ClN3NaO2+[M+Na+] 360.051 0,測量值360.052 9.

9)3ah′ 淡黃色固體；熔點 127～129 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.64(s,1H),7.75(s,2H),7.29(d,J=8.4 Hz,2H),7.05(dd,J=13.5,8.1 Hz,3H),6.78～6.68(m,2H),6.60 (d,J=7.3 Hz,1H),5.84(s,1H).13C NMR(150 MHz,DMSO)δ:178.8,169.3,141.5,134.8,133.1,129.2,128.6,128.4,127.6,126.1,125.8,122.0,118.0,110.0,87.9,62.4;高分辨質(zhì)譜m/z：計算值C18H12ClN3NaO2+[M+Na+] 360.051 0,測量值360.052 9.

10)3ai 淡黃色固體；熔點 167～169 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.57(s,1H),7.73(s,2H),7.54～7.47(m,2H),7.28(t,J=6.9 Hz,2H),7.20(t,J=7.4 Hz,1H),7.08～7.04(m,1H),6.75(d,J=7.7 Hz,1H),6.65～6.54(m,1H),6.02(s,1H).13C NMR(150 MHz,DMSO-d6)δ:179.3,168.5,142.1,133.9,132.4,131.1,129.9,129.5,129.0,127.4,126.5,125.3,124.5,121.2,117.3,109.5,84.4,60.9;高分辨質(zhì)譜m/z：計算值C18H12ClN3NaO2+[M+Na+] 360.051 0,測量值360.052 1.

11)3ba 淡黃色固體；熔點 128～130 ℃;1H NMR(600 MHz,DMSO-d6)δ:7.76(s,2H),7.24～7.16(m,5H),6.99(d,J=7.1 Hz,2H),6.86(d,J=6.8 Hz,2H),5.83(s,1H),3.18(s,3H).13C NMR(150 MHz,DMSO-d6)δ:176.9,169.2,142.6,135.2,129.5,128.8,128.2,127.4,125.4,125.2,124.2,122.1,117.7,108.5,88.3,61.7,26.6;高分辨質(zhì)譜m/z：計算值C19H15N3NaO2+[M+Na+] 340.105 6,測量值340.107 5.

12)3ca 淡黃色固體；熔點 124～126 ℃;1H NMR(600 MHz,CDCl3)δ:7.36～7.28(m,5H),7.13(d,J=6.5 Hz,3H),7.02～6.97(m,3H),6.77(t,J=4.0 Hz,2H),6.59(d,J=7.8 Hz,1H),6.10(s,1H),4.99(dd,J=84.8,15.7 Hz,2H).13C NMR(150 MHz,CDCl3)δ:177.3,169.0,141.6,135.3,134.4,129.0,128.9,128.5,128.2,127.8,127.3,126.7,126.3,126.1,125.3,122.8,116.9,109.2,90.4,62.6,44.3;高分辨質(zhì)譜m/z：計算值C25H19N3NaO2+[M+Na+] 416.136 9,測量值416.139 0.

13)4aa 淡黃色固體；熔點 117～119 ℃;1H NMR(400 MHz,CDCl3)δ:8.73(s,1H),7.22～7.18(m,7H),7.11(s,2H),6.86～6.78(m,2H),6.58(d,J=15.8 Hz,1H),5.89(dd,J=15.8,7.8 Hz,1H),5.53(d,J=7.8 Hz,1H).13C NMR(150 MHz,CDCl3)δ:175.2,168.9,143.0,134.6,133.2,130.9,128.9,127.7,127.2,123.3,122.9,121.9,120.7,116.3,107.9,99.2,90.8,60.7;計算值C20H16N3O2+[M+H+] 330.123 7,測量值330.122 4.

14)4ac 淡黃色固體；熔點 124～126 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.56(s,1H),7.57(s,2H),7.38(s,1H),7.36～7.24(m,4H),7.19(t,J=7.7 Hz,1H),6.99(t,J=7.6 Hz,1H),6.81(d,J=7.7 Hz,1H),6.62(d,J=15.8 Hz,1H),6.20(dd,J=15.9,8.1 Hz,1H),5.28(d,J=8.0 Hz,1H).13C NMR(150 MHz,CDCl3)δ:176.3,169.5,141.0,134.9,133.4,131.5,129.9,127.2,127.2,125.4,124.4,123.8,123.3,123.0,117.7,110.6,91.1,62.0;計算值C20H15ClN3O2+[M+H+] 364.084 7,測量值364.085 4.

15)4ae 淡黃色固體；熔點 133～135 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.60(s,1H),7.59(s,2H),7.24～7.19(m,2H),7.03(d,J=0.6 Hz,1H),6.83(d,J=7.6 Hz,1H),6.55(d,J=15.7 Hz,1H),6.49～6.39(m,3H),5.92～5.79(m,1H),5.31～5.25(m,1H).13C NMR(150 MHz,DMSO-d6)δ:177.9,169.3,168.6,150.5,143.7,142.3,141.3,129.0,128.6,125.7,122.9,122.0,120.3,111.8,110.8,110.0,87.7,61.1;高分辨質(zhì)譜m/z：計算值C25H19N3NaO3+[M+Na+] 432.131 9,測量值432.133 2.

16)4af 淡黃色固體；熔點 143～145 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.43(s,1H),8.17(s,2H),7.72～7.61(m,4H),7.48(d,J=7.4 Hz,1H),7.25(t,J=7.7 Hz,1H),7.09(t,J=7.6 Hz,1H),6.80(d,J=7.6 Hz,1H),6.66(d,J=16.0 Hz,1H),6.54(dd,J=15.9,7.9 Hz,1H),5.40(d,J=7.9 Hz,1H).13C NMR(150 MHz,DMSO-d6)δ:177.2,169.2,147.0,142.2,141.7,132.7,129.3,128.9,127.9,127.0,124.6,124.1,122.4,117.9,109.7,88.5,61.2;高分辨質(zhì)譜m/z：計算值C20H14N4NaO4+[M+Na+] 397.090 7,測量值397.090 9.

17)4af′ 淡黃色固體；熔點 143～145 ℃;1H NMR(600 MHz,DMSO)δ:10.62(s,1H),8.13(s,2H),7.65(s,2H),7.57(d,J=8.8 Hz,2H),7.29(d,J=7.3 Hz,1H),7.22～7.16(m,1H), 6.98(t,J=7.5 Hz,1H),6.82(d,J=7.7 Hz,1H),6.76(d,J=16.0 Hz,1H),6.46(dd,J=15.9,6.8 Hz,1H),5.36(d,J=6.8 Hz,1H).13C NMR(150 MHz,DMSO)δ:178.2,168.6,146.9,141.9,141.4,131.3,129.1,128.7,128.3,127.7,126.2,124.0,121.9,117.7,110.0,87.2,61.1;高分辨質(zhì)譜m/z：計算值C20H14N4NaO4+[M+Na+] 397.090 7,測量值397.091 2.

18)4ag 淡黃色固體；熔點 137～139 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.40(s,1H),7.67(d,J=8.3 Hz,2H),7.63(s,2H),7.57(d,J=8.2 Hz,2H),7.48(d,J=7.4 Hz,1H),7.26～7.22(m,1H),7.09(t,J=7.6 Hz,1H),6.80(d,J=7.7 Hz,1H),6.61(d,J=16.0 Hz,1H),6.45(dd,J=16.0,8.1 Hz,1H),5.37(d,J=8.1 Hz,1H).13C NMR(150 MHz,DMSO-d6)δ:176.8,167.2,140.0,137.9,130.6,127.6,126.9,125.9,125.2,124.7,124.1,123.6,121.8,120.4,116.3,108.5,86.0,59.7;高分辨質(zhì)譜m/z：計算值C21H14F3N3NaO2+[M+Na+] 398.111 1,測量值398.111 3.

19)4ag′ 淡黃色固體；熔點 137～139 ℃;1H NMR(600 MHz,DMSO-d6)δ:10.60(s,1H),7.63(s,2H),7.62(d,J=2.9 Hz,2H),7.51(d,J=8.2 Hz,2H),7.29(d,J=7.4 Hz,1H),7.23～7.13(m,1H),6.99(t,J=7.3 Hz,1H),6.82(d,J=7.7 Hz,1H),6.71(d,J=15.9 Hz,1H),6.35(dd,J=15.9,7.8 Hz,1H),5.34(d,J=7.7 Hz,1H).13C NMR(150 MHz,DMSO-d6)δ:178.6,169.0,141.8,139.7,132.4,129.4,128.8,127.7,127.1,126.5,126.0,125.4,123.6,122.3,118.1,110.3,87.8,61.6;高分辨質(zhì)譜m/z：計算值C21H14F3N3NaO2+[M+Na+]398.111 1,測量值398.111 0.

20)4aj 淡黃色固體；熔點 141～143 ℃;1H NMR(600 MHz,CDCl3)δ:8.94(s,1H),7.35(d,J=7.3 Hz,1H),7.18～7.11(m,4H),7.05～7.00(m,3H),6.71(d,J=8.2 Hz,2H),6.67(d,J=15.6 Hz,1H),6.49(dd,J=15.6,8.0 Hz,1H),5.16(d,J=8.2 Hz,1H),3.72(s,3H).13C NMR(150 MHz,CDCl3)δ:175.6,169.7,149.8,145.0,141.1,140.4,133.9,131.5,128.3,124.6,123.9,120.8,120.1,114.0,113.6,108.1,90.8,62.1,41.4;計算值C21H18N3O3+[M+H+]360.134 3,測量值360.132 8.

21)4ak 淡黃色固體；熔點 129～131 ℃;1H NMR(600 MHz,CDCl3)δ:8.85(s,1H),7.36(d,J=7.5 Hz,2H),7.23(d,J=7.4 Hz,1H),7.13～7.11(m,2H),7.02～6.99(m,5H),6.53(d,J=15.7 Hz,1H),5.84(dd,J=15.8,8.0 Hz,1H),5.18(d,J=7.6 Hz,1H),2.27(s,3H).13C NMR(150 MHz,CDCl3)δ:179.3,169.1,141.1,140.0,138.6,136.9,135.5,132.5,129.3,127.9,127.1,126.9,124.3,120.6,119.3,110.8,89.9,62.1,21.3;高分辨質(zhì)譜m/z：計算值C21H18N3O2+[M+H+]344.139 4,測量值344.139 7.

22)4bb 淡黃色固體；熔點 122～124 ℃;1H NMR(600 MHz,CDCl3)δ:7.42(d,J=7.3 Hz,1H),7.34～7.28(m,3H),7.17(t,J=7.5 Hz,1H),7.08～6.99(m,2H),6.77(d,J=7.7 Hz,1H),6.39～6.30(m,1H),6.27～6.18(m,1H),5.87(d,J=11.6 Hz,2H),5.19(d,J=8.5 Hz,1H),3.13(s,3H).13C NMR(150 MHz,CDCl3)δ:176.1,169.7,143.8,135.4,134.0,131.7,129.7,128.5,128.0,124.1,123.7,122.7,121.5,117.1,108.7,100.0,91.6,61.5,26.6;高分辨質(zhì)譜m/z：計算值C21H16BrN3NaO2+[M+Na+] 444.031 8,測量值422.032 3.

23)4bb′ 淡黃色固體；熔點 122～124 ℃;1H NMR(600 MHz,CDCl3)δ:7.35(d,J=8.4 Hz,2H),7.31～7.28(m,1H),7.26(d,J=0.7 Hz,1H),7.12～7.09(m,1H),7.00～6.93(m,2H),6.82(d,J=7.8 Hz,1H),6.49(d,J=15.8 Hz,1H),5.91～5.81(m,1H),5.49～5.46(m,1H),5.46(d,J=11.0 Hz,2H),3.23(s,3H).13C NMR(150 MHz,CDCl3)δ:176.5,168.6,142.8,134.2,134.1,131.8,129.7,128.3,127.3,125.8,123.2,122.6,122.5,116.7,108.9,100.0,89.5,61.5,27.0;高分辨質(zhì)譜m/z：計算值C21H16BrN3NaO2+[M+Na+]444.031 8,測量值422.032 3.

24)4cb 淡黃色固體；熔點 134～136 ℃;1H NMR(600 MHz,CDCl3)δ:7.34～7.31(m,2H), 7.31～7.27(m,2H),7.18～7.11(m,7H),7.07(t,J=7.8 Hz,2H),6.91(t,J=7.5 Hz,2H),6.62(d,J=7.8 Hz,1H),5.92～5.84(m,1H),5.55～5.49(m,1H),4.93(dd,J=105.5,16.0 Hz,2H).13C NMR(150 MHz,CDCl3)δ:176.8,168.9,141.7,135.5,134.9,134.6,134.0,131.8,129.5,128.8,128.6,128.3,127.6,126.7,125.7,124.2,123.7,123.3,122.7,109.9,89.9,61.8,44.1;高分辨質(zhì)譜m/z：計算值C27H20BrN3NaO2+[M+Na+] 520.063 1,測量值520.065 4.

3 結(jié) 論

本文首次以各種不同取代基的靛紅腈基底物為原料，在常用堿三乙胺的催化下，以二氯甲烷為溶劑，常溫下分別與芳香甲醛、肉桂醛衍生物發(fā)生羥醛縮合/環(huán)化/質(zhì)子遷移串聯(lián)反應(yīng)，以中等至良好的產(chǎn)率高效合成了螺靛紅環(huán)呋喃衍生物.同時，還對該類化合物對真菌的抑制活性也進行了初步研究，發(fā)現(xiàn)部分化合物如化合物4ac能很好地抑制供試菌番茄早疫病菌菌絲生長，而化合物4ag也能強烈抑制供試菌小麥赤霉病菌菌絲生長，它們的抑制率分別為65.0%和85.9%.此外，這些化合物具有2個季碳中心并且同時具有多個可以官能團化的氨基、腈基及雙鍵，為進一步合成其他活性物質(zhì)提供了很好的骨架單元.

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