新型异噁唑拼接3,3'-吡咯螺环双氧化吲哚类化合物的无催化剂合成
|
摘要
以3-异硫氰氧化吲哚与硝基异噁唑缩合的3-烯氧化吲哚,在二氯甲烷中无催化剂条件下于室温发生Michael加成环化反应,获得了8个未见文献报道的异噁唑拼接3,3′-吡咯螺环双氧化吲哚类化合物(3a～3h),产率91%～95%,dr值5/3～3/1,其结构经~1H NMR,~(13)C NMR和HR-MS(ESI-TOF)表征。
Eight new isoxazole-fused 3,3′-spiropyrrolidinylbisoxindoles(3 a～3 h)were synthesized via Michael addition and then cyclization reaction of 3-isothiocyanato oxindoles with 5-isatylidenyl-isoxazoles under catalyst-free and room temperature conditions. The yields and dr of the products were 91%～95% and 5/3～3/1, respectively. The structures were characterized by ~1H NMR, ~(13)C NMR and HR-MS(ESI-TOF).
Eight new isoxazole-fused 3,3′-spiropyrrolidinylbisoxindoles(3 a～3 h)were synthesized via Michael addition and then cyclization reaction of 3-isothiocyanato oxindoles with 5-isatylidenyl-isoxazoles under catalyst-free and room temperature conditions. The yields and dr of the products were 91%～95% and 5/3～3/1, respectively. The structures were characterized by ~1H NMR, ~(13)C NMR and HR-MS(ESI-TOF).
引文
[1] ARUN Y,BHASKAR G,BALACHANDRAN C,et al.Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line[J].Bioorg Med Chem Lett,2013,23:1839-1845.
[2] KIA Y,OSMAN H,KUMAR R S.Synthesis and discovery of novel piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors[J].Bioorg Med Chem,2013,21:1696-1707.
[3] QU J,FANG L,REN X D.Bisindole alkaloids with neural anti-inflammatory activity from gelsemium elegans[J].J Nat Prod,2013,76:2203-2209.
[4] LIU J,YU L F,BREK EATON J,et al.Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression[J].J Med Chem,2011,54 (20):7280-7288.
[5] MAO J,YUAN H,WANG Y,et al.From serendipity to rational antituberculosis drug discovery of mefloquineisoxazole carboxylic acid esters[J].J Med Chem,2009,52:6966-6978.
[6] SUN R,LI Y,XIONG L,et al.Design,synthesis,and insecticidal evaluation of new benzoylureas containing isoxazoline and isoxazole group[J].J Agric Food Chem,2011,59(9):4851-4859.
[7] LIU Y,CUI Z,LIU B,et al.Design,synthesis,and herbicidal activities of novel 2-cyanoacrylates contain- ing isoxazole moieties[J].J Agric Food Chem,2010,58(5):2685-2689.
[8] CHEN W B,WU Z J,HU J,et al.Bisindole alkaloids with neural anti-inflammatory activity from Gelsemium elegans[J].Org Lett,2011,13:2472-2475.
[9] KATO S,YOSHINO T,SHIBASAKI M,et al.Catalytic asymmetric synthesis of spirooxindoles by a Mannich-Type reaction of isothiocyanato oxindoles[J].Angew Chem Int Ed,2012,51:7007-7010.
[10] KATO S,KANAI M,MATSUNAGA S.Catalytic asymmetric synthesis of spirooxindoles via addition of isothiocyanato oxindoles to aldehydes under dinuclear nickel Schiff base catalysis[J].Chem Asian J,2013,8:1768-1771.
[11] LIU X L,HAN W Y,ZHANG X M,et al.Highly efficient and stereocontrolled construction of 3,3′-pyrrolidonyl spirooxindoles via organocatalytic Domino Michael/cyclization reaction[J].Org Lett,2013,15:1246-1249.
[12] HAN W Y,LI S W,WU Z J,et al.3-Isothiocyanato oxindoles serving as powerful and versatile precursors to structurally diverse dispirocyclic thiopyrrolidineoxindoles through a cascade Michael/cyclization process with amino-thiocarbamate catalysts[J].Chem Eur J,2013,19(18):5551- 5556.
[13] HAN W Y,ZHAO J Q,ZUO J,et al.Recent advances of a-isothiocyanato compounds in the catalytic asymmetric reaction[J].Adv Synth Catal,2015,357:3007-3031.
[14] 刘雄伟,周根,姚震,等.异噁唑拼接吡咯螺环氧化吲哚化合物的合成及其抗肿瘤活性[J].合成化学,2016,24(5):389-392.
[15] 彭礼军,周根,韩朔楠,等.新型芳姜黄酮拼合吡咯螺环氧化吲哚类化合物的合成及其抗肿瘤活性[J].合成化学,2016,24(8):669-672.
[16] 陈爽,肖乐,陈智勇,等.新型烷氧基嘧啶拼接3-吡咯螺环氧化吲哚类化合物的合成及其抗肿瘤活性[J].合成化学,2017,25(1):14-17.
[2] KIA Y,OSMAN H,KUMAR R S.Synthesis and discovery of novel piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors[J].Bioorg Med Chem,2013,21:1696-1707.
[3] QU J,FANG L,REN X D.Bisindole alkaloids with neural anti-inflammatory activity from gelsemium elegans[J].J Nat Prod,2013,76:2203-2209.
[4] LIU J,YU L F,BREK EATON J,et al.Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression[J].J Med Chem,2011,54 (20):7280-7288.
[5] MAO J,YUAN H,WANG Y,et al.From serendipity to rational antituberculosis drug discovery of mefloquineisoxazole carboxylic acid esters[J].J Med Chem,2009,52:6966-6978.
[6] SUN R,LI Y,XIONG L,et al.Design,synthesis,and insecticidal evaluation of new benzoylureas containing isoxazoline and isoxazole group[J].J Agric Food Chem,2011,59(9):4851-4859.
[7] LIU Y,CUI Z,LIU B,et al.Design,synthesis,and herbicidal activities of novel 2-cyanoacrylates contain- ing isoxazole moieties[J].J Agric Food Chem,2010,58(5):2685-2689.
[8] CHEN W B,WU Z J,HU J,et al.Bisindole alkaloids with neural anti-inflammatory activity from Gelsemium elegans[J].Org Lett,2011,13:2472-2475.
[9] KATO S,YOSHINO T,SHIBASAKI M,et al.Catalytic asymmetric synthesis of spirooxindoles by a Mannich-Type reaction of isothiocyanato oxindoles[J].Angew Chem Int Ed,2012,51:7007-7010.
[10] KATO S,KANAI M,MATSUNAGA S.Catalytic asymmetric synthesis of spirooxindoles via addition of isothiocyanato oxindoles to aldehydes under dinuclear nickel Schiff base catalysis[J].Chem Asian J,2013,8:1768-1771.
[11] LIU X L,HAN W Y,ZHANG X M,et al.Highly efficient and stereocontrolled construction of 3,3′-pyrrolidonyl spirooxindoles via organocatalytic Domino Michael/cyclization reaction[J].Org Lett,2013,15:1246-1249.
[12] HAN W Y,LI S W,WU Z J,et al.3-Isothiocyanato oxindoles serving as powerful and versatile precursors to structurally diverse dispirocyclic thiopyrrolidineoxindoles through a cascade Michael/cyclization process with amino-thiocarbamate catalysts[J].Chem Eur J,2013,19(18):5551- 5556.
[13] HAN W Y,ZHAO J Q,ZUO J,et al.Recent advances of a-isothiocyanato compounds in the catalytic asymmetric reaction[J].Adv Synth Catal,2015,357:3007-3031.
[14] 刘雄伟,周根,姚震,等.异噁唑拼接吡咯螺环氧化吲哚化合物的合成及其抗肿瘤活性[J].合成化学,2016,24(5):389-392.
[15] 彭礼军,周根,韩朔楠,等.新型芳姜黄酮拼合吡咯螺环氧化吲哚类化合物的合成及其抗肿瘤活性[J].合成化学,2016,24(8):669-672.
[16] 陈爽,肖乐,陈智勇,等.新型烷氧基嘧啶拼接3-吡咯螺环氧化吲哚类化合物的合成及其抗肿瘤活性[J].合成化学,2017,25(1):14-17.