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CN107311849B - 一种环桥联螺茚酮类化合物的合成方法 - Google Patents

一种环桥联螺茚酮类化合物的合成方法 Download PDF

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CN107311849B
CN107311849B CN201710606444.3A CN201710606444A CN107311849B CN 107311849 B CN107311849 B CN 107311849B CN 201710606444 A CN201710606444 A CN 201710606444A CN 107311849 B CN107311849 B CN 107311849B
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颜朝国
石荣国
韩莹
孙晶
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Abstract

一种环桥联螺茚酮类化合物的合成方法，属于有机合成技术领域，在溶剂和催化剂存在的条件下，将芳香醛与多分子的1,3‑茚满二酮发生多米诺反应，反应结束后用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析，得到环桥联螺茚酮类化合物。其中，溶剂为乙醇或甲醇；所述催化剂为三乙胺、哌啶、三乙烯二胺或1,8‑二氮杂二环十一碳‑7‑烯。本发明底物拓展范围大、原料易得、操作简单、无需过渡金属催化剂的条件即可合成。

Description

一种环桥联螺茚酮类化合物的合成方法
技术领域
本发明属于有机合成技术领域。
背景技术
1,3-茚满二酮具有亲核性的亚甲基以及亲电性的羰基，自身较容易发生多分子的缩合反应(Jacob, K.; Sigalov, M,; et al. Self-Condensation of 1,3-Indandione:A Reinvestigation. [J]. Eur. J. Org. Chem. 2000, 2047-2055)。1,3-茚满二酮的三聚体具有大的共轭体系，在光电材料领域具有很多的应用。在2012年Martín课题组报道了合成1,3-茚满二酮三聚体及其衍生物将其作为碗形电子供体，用作光电材料吸收太阳能（Isla, H.; Martín, N.; et al. Bowl-shape electron donors with absorptions inthe visible range of the solar spectrum and their supramolecular assemblieswith C60 [J]. Chem. Sci., 2012, 3, 498-508）。
螺茚酮化合物在天然产物、药物、农药等生物活性分子中亦广泛存在，且表现出抗肿瘤、抗高血压、抗过敏等突出的生理活性。茚酮并环衍生物同样表现出多种生物和药理活性，如从番荔枝中分离出来的生物碱具有茚酮吡啶骨架，其衍生物被发现具有磷酸二酯酶活性和抑制腺苷A2a受体结合能力，用于治疗神经退行性疾病和炎症相关的疾病(Aran go,G. J.;Cortes, D.; et al., Azafluorenones from Oxandra cf. major andbiogenetic considerations [J]. Phytochemistry, 1987, 26, 2093-2098)。
1,3-茚满二酮可以用于合成螺茚酮类化合物，但是由于1,3-茚满二酮底物的特殊性，衍生化相对困难，而文献所报道的方法在不同程度上存在一些问题，如使用强酸，强碱性溶剂，反应时间较长，产率较低，底物拓展范围小等。因此，利用1,3-茚满二酮合成螺茚酮类化合物，并进行衍生化合成环桥联螺茚酮类化合物具有重要的意义。
发明内容
本发明所要解决的技术问题在于克服上述问题，提供一种底物拓展范围大、原料易得、操作简单、无需过渡金属催化剂的条件即可合成得到环桥联螺茚酮类化合物。
本发明技术方案是：在溶剂和催化剂存在的条件下，将芳香醛与多分子的1,3-茚满二酮发生多米诺反应，反应结束后用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析，得到环桥联螺茚酮类化合物。其中，溶剂为乙醇或甲醇；所述催化剂为三乙胺、哌啶、三乙烯二胺或1,8-二氮杂二环十一碳-7-烯。
反应通式为：
Figure 718208DEST_PATH_IMAGE001
其中：R基团为C1～C4烷基取代苯基、卤代苯基、硝基取代的苯基、吡啶基或C1～C3的烷基中的任意一种。
本发明的机理为：多分子的1,3-茚满二酮自身缩合生成中间体A，中间体A经过电环化生成B，进一步[1,5]-H迁移形成C，1,3-茚满二酮与醛缩合形成的E与中间体C发生Diels-Alder反应，生成最终的环桥联螺茚酮类化合物，反应产率可达43%～74%。
本发明详细过程式如下：
Figure 767811DEST_PATH_IMAGE002
本发明以易得的芳香醛、多分子1,3-茚满二酮为原料，在无过渡金属催化剂存在下，不需无水无氧反应条件，不需要加入强酸或者强碱，所用的原料、溶剂与催化剂均不需要预先处理。该合成方法操作简便、收率高且环境友好。
进一步地，本发明所述R为苯基、4-甲基苯基、4-甲氧基苯基、4-硝基苯基、4-卤代苯基、3-甲基苯基、3-甲氧基苯基、3-硝基苯基、3-卤代苯基、2-甲氧基苯基、2-卤代苯基、2-吡啶基、3-吡啶基、4-吡啶基、甲基、乙基、丙基或丁基中的任意一种，其合成产率可达43%～76%。
更优选地，所述芳香醛为苯甲醛、间甲氧基苯甲醛、间氯基苯甲醛、间甲基苯甲醛、对硝基苯甲醛、4-吡啶甲醛、间氟苯甲醛或对溴苯甲醛。采用这些具体物质为本发明的芳香醛与多分子1,3-茚满二酮进行反应，可以获得更高的收率。
所述溶剂为乙醇或甲醇中的至少任意一种，优选为乙醇。当R为苯基，用乙醇作为溶剂，产率可达71%。
所述催化剂为三乙胺、哌啶、三乙烯二胺（DABCO）或1,8-二氮杂二环十一碳-7-烯（DBU）。优选三乙胺或哌啶。当R为2-甲氧基苯基，用三乙胺作为溶剂，产率可达74%。
所述芳香醛和催化剂的投料摩尔比为1∶1～4。催化剂用量小于1∶1，反应几乎不进行；超过4倍用量，产物收率不再增加。
所述芳香醛与1,3-茚满二酮投料摩尔比为1∶4～5，在该摩尔比下反应产率可达68%～74%。
所述多米诺反应的温度条件为30～80℃。鉴于优选溶剂为乙醇，更优选地，反应温度为为78℃，常压下乙醇回流（78℃），反应时间可缩短至5小时。该温度下，反应效率最高。温度过高，时间过长，则副产物增加；温度过低，时间过短，则反应不完全。反应收率最高可达到74%。
具体实施方式
下面结合实施例对本发明进一步详细说明，但本发明的保护范围不仅限于这些实施例。
实施例1：制备结构式如下的4b'-羟基-17'-苯基-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 567139DEST_PATH_IMAGE003
在50 mL圆底烧瓶中加入0.053g (0.5mmol)苯甲醛、0.321g (2.2mmol)1,3-茚满二酮，再加入20 mL乙醇，再加0.101g (1.0mmol)三乙胺，在加热回流（78℃）的条件下进行多米诺反应5小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得到纯4b'-羟基-17'-苯基-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为71%。
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.66 (d, J = 7.6 Hz, 1H, ArH), 8.13 (d, J= 7.6 Hz, 1H, ArH), 7.90 (t, J = 7.6 Hz, 1H, ArH), 7.81 (t, J = 6.8 Hz, 1H,ArH), 7.67-7.65 (m, 1H, ArH), 7.64-7.62 (m, 2H, ArH), 7.61-7.59 (m, 1H, ArH),7.43 (d, J = 7.6 Hz, 1H, ArH), 7.36 (d, J = 7.2 Hz, 1H, ArH), 7.32 (d, J =7.2 Hz, 1H, ArH), 7.29-7.24 (m, 2H, ArH), 7.20 (d, J = 7.6 Hz, 2H, ArH), 7.15(d, J = 8.0 Hz, 1H, ArH), 7.04 (d, J = 7.6 Hz, 1H, ArH), 6.90 (s, 1H, OH),6.86 (t, J = 7.6 Hz, 1H, ArH), 6.74 (t, J = 7.6 Hz, 2H, ArH), 6.47-6.44 (m,1H, ArH), 5.36 (s, 1H, CH), 4.43 (s, 1H, CH); 13C NMR (150 MHz, DMSO-d 6 ) δ:201.7, 200.4, 199.0, 196.8, 188.2, 152.4, 146.0, 144.2, 142.3, 141.9, 141.4,140.7, 140.4, 137.1, 136.8, 136.6, 136.0, 135.2, 134.9, 134.7, 132.9, 129.6,129.1, 128.3, 127.7, 127.4, 127.1, 125.6, 125.2, 123.7, 123.2, 123.1, 122.3,121.8, 84.1, 65.5, 62.2, 58.3, 54.3, 52.2; IR (KBr) υ:3469, 3065, 2962, 1703,1656, 1592, 1459, 1251, 1067, 767, 701cm-1; MS (m/z): HRMS (ESI) C43H25O6 ([M+H]+) 理论值637.1464，实测值637.1627。
实施例2：制备结构式如下的4b'-羟基-17'-(2-甲氧苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 887262DEST_PATH_IMAGE004
在50 mL圆底烧瓶中加入0.068g (0.5mmol)间甲氧基苯甲醛、0.365g (2.5mmol)1,3-茚满二酮，再加入15 mL甲醇，再加0.127g (1.5mmol) 三乙胺，在50℃的条件下进行多米诺反应8小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得4b'-羟基-17'-(2-甲氧苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为74%。
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.59 (d, J = 7.6 Hz, 1H, ArH), 8.12 (d, J= 7.6 Hz, 1H, ArH), 7.88 (t, J = 7.6 Hz, 1H, ArH), 7.77 (t, J = 8.0 Hz, 1H,ArH), 7.73 (d, J = 7.6 Hz, 1H, ArH), 7.65 (t, J = 7.2 Hz, 1H, ArH), 7.62-7.56(m, 2H, ArH), 7.44-7.40 (m, 1H, ArH), 7.34 (t, J = 7.6 Hz, 1H, ArH), 7.31-7.27 (m, 1H, ArH), 7.27-7.25 (m, 1H, ArH), 7.22-7.19 (m, 2H, ArH), 7.16 (d, J= 7.6 Hz, 1H, ArH), 7.00 (d, J = 7.6 Hz, 1H, ArH), 6.86-6.81 (m, 1H, ArH),6.80 (s, 1H, OH), 6.38 (d, J = 8.4 Hz, 1H, ArH), 6.30 (d, J = 7.6 Hz, 1H,ArH), 6.16-6.14 (m, 1H, ArH), 5.87 (s, 1H, CH), 4.52 (s, 1H, CH), 3.03 (s,3H, OCH3); 13C NMR (150 MHz, DMSO-d 6 ) δ: 203.6, 202.2, 199.7, 196.1, 188.5,156.1, 151.4, 145.7, 144.2, 143.3, 142.6, 141.8, 141.5, 140.5, 137.6, 136.1,135.5, 135.3, 135.2, 135.0, 134.4, 132.2, 129.6, 129.4, 129.0, 128.6, 128.5,125.6, 124.7, 124.5, 123.9, 123.4, 123.0, 122.8, 122.4, 120.4, 109.6, 85.1,63.9, 62.3, 58.9, 55.1, 54.2, 44.4; IR (KBr) υ: 3390, 3066, 2930, 2834, 1708,1653, 1592, 1461, 1333, 1194, 1063, 760, 701 cm-1; MS (m/z): HRMS (ESI)C44H27O7 ([M+ H]+) 理论值为667.1751，实测值为667.1753。
实施例3：制备结构式如下的4b'-羟基-17'-(2-氯苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 113844DEST_PATH_IMAGE005
在50 mL圆底烧瓶中加入0.070g (0.5mmol)间氯基苯甲醛、0.292g (2.0mmol) 1,3-茚满二酮，再加入15 mL甲醇，再加0.127g (1.5mmol) 哌啶，在40℃的条件下进行多米诺反应10小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得4b'-羟基-17'-(2-氯苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为68%，
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.63 (d, J = 8.0 Hz, 1H, ArH), 8.13 (d, J= 7.6 Hz, 1H, ArH), 7.91 (t, J = 7.6 Hz, 1H, ArH), 7.80 (t, J = 7.6 Hz, 1H,ArH), 7.71-7.69 (m, 1H, ArH), 7.67-7.64 (m, 3H, ArH), 7.42 (t, J = 7.2 Hz,1H, ArH), 7.37 (d, J = 7.2 Hz, 1H, ArH), 7.34-7.33 (m, 1H, ArH), 7.31-7.25(m, 2H, ArH), 7.23-7.15 (m, 3H, ArH), 7.13 (d, J = 7.6 Hz, 1H, ArH), 6.97-6.95 (m, 1H, ArH), 6.94 (s, 1H, OH), 6.82 (t, J = 8.0 Hz, 1H, ArH), 6.47-6.46(m, 1H, ArH), 5.35 (s, 1H, CH), 4.39 (s, 1H, CH); 13C NMR (150 MHz, DMSO-d 6 )δ: 203.0, 202.1, 199.4, 195.9, 188.3, 151.4, 145.2, 143.6, 143.4, 142.8,141.6, 141.4, 140.1, 137.5, 136.5, 136.3, 136.1, 135.9, 135.3, 135.2, 134.4,133.7, 132.3, 130.4, 129.7, 129.2, 129.1, 128.6, 128.0, 125.7, 124.5, 124.2,123.5, 123.3, 123.2, 123.1, 84.6, 65.5, 62.4, 58.0, 55.4, 52.6; IR (KBr) υ:3364, 3066, 2961, 1703, 1659, 1590, 1464, 1194, 888, 762, 701cm-1; MS (m/z):HRMS (ESI) C43H24ClO6 ([M+H]+): 理论值671.1256，实测值671.1237。
实施例4：制备结构式如下的4b'-羟基-17'-(3-甲基苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 778306DEST_PATH_IMAGE006
在50 mL圆底烧瓶中加入0.060g (0.5mmol)间甲基苯甲醛、0.438g (3.0mmol) 1,3-茚满二酮，再加入25 mL甲醇，再加0.224g (2.0mmol) 三乙烯二胺（DABCO），在80℃的条件下进行多米诺反应5小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得4b'-羟基-17'-(3-甲基苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为63%。
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.65 (d, J = 7.6 Hz, 1H, ArH), 8.12 (d, J= 7.6 Hz, 1H, ArH), 7.89 (t, J = 7.6 Hz, 1H, ArH), 7.80 (t, J = 7.2 Hz, 1H,ArH), 7.69-7.61 (m, 4H, ArH), 7.44 (t, J = 7.2 Hz, 1H, ArH), 7.38-7.33 (m,2H, ArH), 7.32-7.25 (m, 2H, ArH), 7.22 (d, J = 8.0 Hz, 2H, ArH), 7.17 (d, J =7.6 Hz, 1H, ArH), 7.06 (d, J = 7.6 Hz, 1H, ArH), 6.90 (s, 1H, OH), 6.69-6.66(m, 1H, ArH), 6.64-6.61 (m, 1H, ArH), 6.24-6.17 (m, 1H, ArH), 5.32 (s, 1H,CH), 4.43 (s, 1H, CH), 1.72 (s, 3H, CH3); 13C NMR (150 MHz, DMSO-d 6 ) δ: 203.3,202.4, 199.7, 196.1, 188.5, 151.6, 145.6, 143.8, 143.7, 143.0, 141.7, 141.4,140.3, 137.6, 137.4, 136.2, 136.0, 135.5, 135.3, 135.2, 134.4, 133.8, 132.1,129.6, 129.1, 128.5, 128.4, 127.7, 125.6, 124.4, 124.2, 123.4, 123.2, 123.0,122.9, 84.7, 65.8, 62.6, 58.1, 55.1, 53.4, 20.9; IR (KBr) υ:3512, 3067, 2922,1704, 1655, 1590, 1460, 1365, 1189, 1066, 771, 701 cm-1; MS (m/z): HRMS (ESI)C44H27O6 ([M+H]+) 理论值651.1789，实测值651.1783。
实施例5：制备结构式如下的4b'-羟基-17'-(4-硝基苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 850167DEST_PATH_IMAGE007
在50 mL圆底烧瓶中加入0.076g (0.5mmol)对硝基苯甲醛、0.511g (3.5mmol) 1,3-茚满二酮，再加入25 mL乙醇，再加0.056g (0.5mmol) 三乙烯二胺（DABCO），在78℃的条件下进行多米诺反应5小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得4b'-羟基-17'-(4-硝基苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为49%。
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.63 (d, J = 7.6 Hz, 1H, ArH), 8.13 (d, J= 7.6 Hz, 1H, ArH), 7.92 (t, J = 7.2 Hz, 1H, ArH), 7.81 (t, J = 7.6 Hz, 1H,ArH), 7.70-7.67 (m, 3H, ArH), 7.65-7.63 (m, 3H, ArH), 7.43-7.41 (m, 1H, ArH),7.38 (d, J = 6.0 Hz, 1H, ArH), 7.35 (d, J = 7.6 Hz, 1H, ArH), 7.32-7.28 (m,2H, ArH), 7.24 (d, J = 7.2 Hz, 1H, ArH), 7.17-7.12 (m, 3H, ArH), 7.03 (s, 1H,OH), 6.83-6.75 (m, 1H, ArH), 5.54 (s, 1H, CH), 4.34 (s, 1H, CH); 13C NMR (100MHz, DMSO-d 6 ) δ: 202.6, 201.7, 199.2, 195.9, 188.1, 151.1, 147.1, 144.8,143.4, 143.2, 142.4, 141.8, 141.4, 141.2, 139.9, 137.4, 136.7, 136.6, 136.2,135.3, 134.5, 132.6, 131.0, 129.8, 129.3, 128.6, 125.6, 124.6, 124.1, 123.6,123.4, 123.3, 123.2, 123.0, 84.6, 65.2, 62.4, 58.0, 55.6, 52.0; IR (KBr) υ:3469, 3061, 1702, 1653, 1588, 1462, 1249, 770, 701cm-1; MS (m/z): HRMS (ESI)C43H24NO8 ([M+H]+) 理论值682.1496，实测值682.1485。
实施例6：制备结构式如下的4b'-羟基-17'-(2-吡啶)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 290376DEST_PATH_IMAGE008
在50 mL圆底烧瓶中加入0.054g (0.5mmol) 2-吡啶甲醛、0.511g (3.5mmol) 1,3-茚满二酮，再加入25 mL乙醇，再加入0.056g (0.5mmol) 三乙烯二胺（DABCO），在30℃的条件下进行多米诺反应5小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得4b'-羟基-17'-(2-吡啶)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为43%。
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.52 (d, J = 7.2 Hz, 1H, ArH), 8.18 (d, J= 7.6 Hz, 1H, ArH), 7.94 (t, J = 7.6 Hz, 1H, ArH), 7.73-7.65 (m, 4H, ArH),7.63-7.56 (m, 2H, ArH), 7.34-7.28 (m, 3H, ArH), 7.25-7.18 (m, 4H, ArH), 7.12(d, J = 7.2 Hz, 1H, ArH), 7.09 (d, J = 7.6 Hz, 1H, ArH), 6.86-6.84 (m, 1H,ArH), 6.82 (s, 1H, OH), 6.42 (d, J = 8.0 Hz, 1H, ArH), 5.63 (s, 1H, CH), 4.26(s, 1H, CH); 13C NMR (100 MHz, DMSO-d 6 ) δ: 202.2, 200.7, 200.1, 196.5, 188.4,156.1, 152.8, 148.4, 146.7, 145.8, 142.5, 142.3, 142.1, 141.6, 141.1, 137.3,137.2, 137.1, 136.5, 135.2, 135.1, 134.8, 132.9, 132.7, 129.9, 129.4, 127.4,126.2, 125.9, 124.0, 123.8, 123.0, 122.9, 122.6, 122.4, 122.1, 84.3, 64.2,61.4, 58.7, 55.1, 53.6; IR (KBr) υ:3427, 3056, 2923, 1705, 1661, 1592, 1465,1251, 778, 702 cm-1; MS (m/z): HRMS (ESI) C42H24NO6 ([M+H]+) 理论值638.1598，实测值638.1620。
实施例7：制备结构式如下的4b'-羟基-17'-(2-氟苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 914956DEST_PATH_IMAGE009
在50 mL圆底烧瓶中加入0.062g (0.5mmol) 间氟苯甲醛、0.511g (3.5mmol) 1,3-茚满二酮，再加入25 mL乙醇，再加入0.152g (1.0mmol) 1,8-二氮杂二环十一碳-7-烯(DBU)，在78℃的条件下进行多米诺反应5小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得4b'-羟基-17'-(2-氟苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为58%。
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.63 (d, J = 7.6 Hz, 1H, ArH), 8.12 (d, J= 7.6 Hz, 1H, ArH), 7.90 (t, J = 7.6 Hz, 1H, ArH), 7.80 (t, J = 7.2 Hz, 1H,ArH), 7.70 (d, J = 7.2 Hz, 1H, ArH), 7.66-7.64 (m, 3H, ArH), 7.43 (t, J = 7.2Hz, 1H, ArH), 7.37 (d, J = 7.6 Hz, 1H, ArH), 7.33 (d, J = 6.8 Hz, 1H, ArH),7.31-7.21 (m, 3H, ArH), 7.20-7.15 (m, 2H, ArH), 7.12 (t, J = 8.0 Hz, 1H,ArH), 6.95 (s, 1H, OH), 6.87-6.81 (m, 1H, ArH), 6.76-6.71 (m, 1H, ArH), 6.38-6.37 (m, 1H, ArH), 5.37 (s, 1H, CH), 4.40 (s, 1H, CH); 13C NMR (100 MHz, DMSO-d 6 ) δ: 203.1, 202.1, 199.5, 196.0, 188.3, 161.9 (d, J = 246.0 Hz), 151.4,145.2, 143.6, 143.4, 142.8, 141.6, 141.4, 140.1, 137.5, 136.6 (d, J = 7.2Hz), 136.5, 136.3, 135.8, 135.3, 135.2, 134.5, 132.3, 129.7, 129.4 (d, J =8.1 Hz), 129.2, 128.6, 125.8, 125.6, 124.5, 124.2, 123.5, 123.3, 123.2,123.0, 117.2 (d, J = 25.6 Hz), 114.9 (d, J = 20.7 Hz), 84.7, 65.5, 62.5,58.0, 55.3, 52.7; IR (KBr) υ: 3471, 3072, 2922, 1703, 1658, 1591, 1459, 1255,955, 884, 773, 698 cm-1; MS (m/z): HRMS (ESI) C43H24FO6 ([M+H]+) 理论值655.1552，实测值655.1551。
实施例8：制备结构式如下的4b'-羟基-17'-(4-溴苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮：
Figure 565249DEST_PATH_IMAGE010
在50 mL圆底烧瓶中加入0.092g (0.5mmol) 对溴苯甲醛、0.511g (3.5mmol) 1,3-茚满二酮，再加入25 mL乙醇，再加入0.152g (1.0mmol) 1,8-二氮杂二环十一碳-7-烯(DBU)，在78℃的条件下进行多米诺反应5小时。
反应结束后将溶剂蒸发浓缩，利用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析提纯处理，即可得4b'-羟基-17'-(4-溴苯基)-4b',14c'-二氢-15'H-螺[茚-2,16'-[4c,14b]乙基二茚[1,2-a:1',2'-c]芴]-1,3,5',10',15'-五酮，其分离收率为60%。
结构表征数据如下：
1H NMR (400 MHz, DMSO-d 6 ) δ: 8.64 (d, J = 7.6 Hz, 1H, ArH), 8.14 (d, J= 7.6 Hz, 1H, ArH), 7.95-7.91 (m, 1H, ArH), 7.83-7.80 (m, 1H, ArH), 7.73-7.69(m, 2H, ArH), 7.68-7.66 (m, 2H, ArH), 7.47-7.43 (m, 1H, ArH), 7.41-7.37 (m,1H, ArH), 7.36-7.33 (m, 1H, ArH), 7.32-7.27 (m, 2H, ArH), 7.25-7.17 (m, 4H,ArH), 7.03 (d, J = 8.8 Hz, 2H, ArH), 6.96 (s, 1H, OH), 6.49-6.43 (m, 1H,ArH), 5.38 (s, 1H, CH), 4.41 (s, 1H, CH); 13C NMR (100 MHz, DMSO-d 6 ) δ: 203.1,202.0, 199.4, 196.1, 188.3, 151.3, 145.2, 143.5, 143.4, 142.7, 141.5, 141.3,140.0, 137.4, 136.4, 136.3, 135.8, 135.3, 135.2, 134.4, 133.1, 132.3, 131.7,131.0, 129.7, 129.2, 128.5, 125.5, 124.5, 124.1, 123.5, 123.3, 123.2, 123.1,122.0, 84.6, 65.4, 62.5, 58.0, 55.3, 52.4; IR (KBr) υ: 3478, 3071, 2956,1703, 1657, 1591, 1250, 827, 765, 704 cm-1; MS (m/z): HRMS (ESI) C43H24ClO6 ([M+H]+) 理论值715.0751，实测值715.0719。

Claims (6)

1.一种环桥联螺茚酮类化合物的合成方法，其特征在于：在溶剂和催化剂存在的条件下，将芳香醛与多分子的1,3-茚满二酮发生多米诺反应，反应结束后用乙酸乙酯和石油醚的混合溶剂进行硅胶柱层析，得到环桥联螺茚酮类化合物；
所述溶剂为乙醇或甲醇；所述催化剂为三乙胺、哌啶、三乙烯二胺或1,8-二氮杂二环十一碳-7-烯；
所述芳香醛与1,3-茚满二酮投料摩尔比为1∶4～5；所述多米诺反应的温度条件为30～80℃；
反应通式为：
Figure 445996DEST_PATH_IMAGE001
其中：芳香醛中R为C1～C4烷基取代苯基、卤代苯基、硝基取代的苯基或吡啶基。
2.根据权利要求1所述环桥联螺茚酮类化合物的合成方法，其特征在于：所述芳香醛中R为苯基、4-甲基苯基、4-硝基苯基、4-卤代苯基、3-甲基苯基、3-硝基苯基、3-卤代苯基、2-卤代苯基、2-吡啶基、3-吡啶基或4-吡啶基。
3.根据权利要求2所述环桥联螺茚酮类化合物的合成方法，其特征在于：所述芳香醛为苯甲醛、邻氯苯甲醛、间甲基苯甲醛、对硝基苯甲醛、2-吡啶甲醛、间氟苯甲醛或对溴苯甲醛。
4.根据权利要求1所述环桥联螺茚酮类化合物的合成方法，其特征在于：所述溶剂为乙醇。
5.根据权利要求1所述环桥联螺茚酮类化合物的合成方法，其特征在于：所述芳香醛和催化剂的投料摩尔比为1∶1～4。
6.根据权利要求5所述环桥联螺茚酮类化合物的合成方法，其特征在于：所述多米诺反应的温度条件为78℃。
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CN105250260A (zh) * 2015-11-19 2016-01-20 成都中医药大学 一种1,3-茚满二酮螺环化合物的抗肿瘤用途
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CN104557559A (zh) * 2015-01-14 2015-04-29 成都中医药大学 茚满二酮手性环己烷螺环化合物及其制备方法与用途
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