对甲苯磺酸控制的β-咔啉衍生物微波辅助合成
|
摘要
采用对甲苯磺酸(Ts OH)作为添加剂,在微波反应器中使色氨酸与醛类5 min内完全转化为相应的1-取代-四氢-β-咔啉衍生物。实验表明:在色氨酸与脂肪族醛或芳香族醛发生反应的过程中,质子酸作为添加剂起到了关键性作用。当该反应采用Ts OH作为添加剂时,脂肪族醛与色氨酸反应得到了较好的结果,反应生成的1-取代-四氢-β-咔啉衍生物产率高达95%。1-取代-四氢-β-咔啉衍生物作为合成β-咔啉衍生物的关键中间体,其可在MnO2或酸性K2Cr2O7的氧化作用下合成β-咔啉衍生物。
p-Toluenesulfonic acid( Ts OH) was used as an additive to completely convert tryptophan and aldehydes into corresponding 1-substituted-tetrahydro-β-caroline derivatives in 5 min in a microwave reactor. Experiments showed that protonic acid played a key role in the reaction of tryptophan with aliphatic aldehydes or aromatic aldehydes.When Ts OH was used as an additive in the reaction,the reaction of aliphatic aldehydes with tryptophan gave better results.1-Substituted-tetrahydro-β-caroline derivatives were produced with yields up to 95% by the reaction of aliphatic aldehydes with tryptophan.The 1-substituted-tetrahydro-β-carbaline derivatives were employed as the key intermediate for the synthesis of β-carbaline derivatives,which can be synthesizedβ-carboline derivatives under the oxidation of MnO_2 or acidic K_2Cr_2O_7.
p-Toluenesulfonic acid( Ts OH) was used as an additive to completely convert tryptophan and aldehydes into corresponding 1-substituted-tetrahydro-β-caroline derivatives in 5 min in a microwave reactor. Experiments showed that protonic acid played a key role in the reaction of tryptophan with aliphatic aldehydes or aromatic aldehydes.When Ts OH was used as an additive in the reaction,the reaction of aliphatic aldehydes with tryptophan gave better results.1-Substituted-tetrahydro-β-caroline derivatives were produced with yields up to 95% by the reaction of aliphatic aldehydes with tryptophan.The 1-substituted-tetrahydro-β-carbaline derivatives were employed as the key intermediate for the synthesis of β-carbaline derivatives,which can be synthesizedβ-carboline derivatives under the oxidation of MnO_2 or acidic K_2Cr_2O_7.
引文
[1]BOUCLE S,MELIN C,CLASTRE M,et al. Design,synthesis and evaluation of new marine alkaloid-derived pentacyclic structures with anti-tumoral potency[J]. Marine Drugs,2015,13(1):655-665.
[2]SRIVASTAVA S K,AGARWAL A,CHAUHAN P M S,et al.Potent 1,3-disubstituted-9H-pyrido[3,4-b]indoles as new lead compounds in antifilarial chemotherapy[J].Med.Chem.,1999,42(9):1 667-1 672.
[3]MILLER J F,TURNER E M,SHERRILL R G,et al.Substituted tetrahydro-β-carbolines as potential agents for the treatment of human papillomavirus infection[J]. Bioorg.Med.Chem.Lett.,2010,20(1):256-259.
[4]RENIERS J,ROBERT S,FREDERICK R,et al.Synthesis and evaluation ofβ-carboline derivatives as potential monoamine oxidase inhibitors[J]. Bioorg. Med. Chem.,2011,19(1):134-144.
[5]KUO P C,SHI L S,DAMU A G,et al.Cytotoxic and antimalarialβ-carboline alkaloids from the roots of eurycoma longifolia[J].J.Nat.Prod.,2003,66(10):1 324-1 327.
[6]ASHOK P,CHANDER S,BALZARINI J,et al. Design,synthesis of newβ-carboline derivatives and their selective anti-HIV-2 activity[J]. Bioorg. Med. Chem. Lett.,2015,25(6):1 232-1 235.
[7]ISHIDA J,WANG H K,BASTOW K F,et al.Antitumor agents 201.1,cytotoxicity of harmine andβ-carboline analogs[J]. Bioorg. Med. Chem. Lett.,1999,9(23):3 319-3 324.
[8]BARSANTI P A,WANG W,NI Z J,et al.The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5[J].Bioorg.Med.Chem.Lett.,2010,20(1):157-160.
[9]LIU L,MA Y Y,WANG K,et al.Anti-tumor and antimicrobial activities ofβ-carbolines[J]. Chem. J. Chinese U.,2018,39(4):674-680.
[10]周鑫鑫,周宁,刘长春.单取代/双取代氧化吲哚衍生物的合成研究[J].化学试剂,2018,40(1):97-102.
[11]MULCAHY S P,VARELAS J G.Three-step synthesis of an annulatedβ-carboline via palladium catalysis[J].Cheminform,2013,54(48):6 599-6 601.
[12]SUDHAKAR M,SADHANA S,ABUBAKAR W,et al.Discovery of a marine-derived bis-indole alkaloid fascaplysin,as a newclass of potent P-glycoprotein inducer and establishment of its structure eactivity relationship[J].Eur.J.Med.Chem.,2016,107(1):1-11.
[13]MEESALA R,ARSHAD A S M,MORDI M N,et al.Iodine-catalyzed one-pot decarboxylative aromatization of tetrahydro-β-carbolines[J].Tetrahedron,2016,72(52):8 537-8 541.
[14]DONG J,SHI X X,YAN J J,et al.Efficient and practical one-pot conversions of N-tosyltetrahydroisoquinolines into isoquinolines and of N-tosyltetrahydro-β-carbolines intoβ-carbolines through tandemβ-elimination and aromatization[J]. Eur. J. Org. Chem.,2010,2 010(36):6 987-6 992.
[15]TADA M,SAEKI H,OIKAWA A.The identification of 3-amino-9H-pyrido[3,4-b]indole derivatives in L-tryptophan pyrolysates[J].Bull.Chem.Soc.Jpn.,1983,56(5):1 450-1 554.
[16]GUO L,CAO R H,FAN W X,et al. Design,synthesis and in vitro antitumor activities of novel bivalentβ-carbolines[J]. Chem. J. Chinese U.,2005,40(10):991-1 001.
[17]GUO L,FAN W X,GAN Z Y,et al.Design and synthesis of 1-substituted-β-carboline derivatives as potential anticancer agents[J]. Chin. Pharm.,2015,26(14):1 869-1 885.
[18]ZENI G,LAROCK R C. Synthesis of heterocycles via palladiumπ-olefin andπ-alkyne chemistry[J]. Chem.Rev.,2004,104(5):2 285-2 309.
[19]SONG Y C,WANG J,DENG Y,et al.β-Carbolines as specific inhibitors of cyclin-dependent kinases[J].Med.Chem.Lett.,2002,12(7):1 129-1 132.
[20]WANG Z X,XIANG J C,CHENG Y,et al.Direct biomimetic synthesis ofβ-carboline alkaloids from two amino acids[J].J.Org.Chem.,2018,83(19):12 247-12 254.
[21]IVANOV I,NIKOLOVA S,STAKOVA-ABEGHE S. A simple method for the synthesis of 1-substitutedβ-carboline derivatives from tryptamine and carboxylic acids in polyphosphoric acid[J]. Heterocycles,2005,65(10):2 483-2 492.
[22]GILSON Z,RICHARD C L.Synthesis of heterocycles via palladium-catalyzed oxidative addition[J]. Chem. Rev.,2006,106(11):4 644-4 680.
[2]SRIVASTAVA S K,AGARWAL A,CHAUHAN P M S,et al.Potent 1,3-disubstituted-9H-pyrido[3,4-b]indoles as new lead compounds in antifilarial chemotherapy[J].Med.Chem.,1999,42(9):1 667-1 672.
[3]MILLER J F,TURNER E M,SHERRILL R G,et al.Substituted tetrahydro-β-carbolines as potential agents for the treatment of human papillomavirus infection[J]. Bioorg.Med.Chem.Lett.,2010,20(1):256-259.
[4]RENIERS J,ROBERT S,FREDERICK R,et al.Synthesis and evaluation ofβ-carboline derivatives as potential monoamine oxidase inhibitors[J]. Bioorg. Med. Chem.,2011,19(1):134-144.
[5]KUO P C,SHI L S,DAMU A G,et al.Cytotoxic and antimalarialβ-carboline alkaloids from the roots of eurycoma longifolia[J].J.Nat.Prod.,2003,66(10):1 324-1 327.
[6]ASHOK P,CHANDER S,BALZARINI J,et al. Design,synthesis of newβ-carboline derivatives and their selective anti-HIV-2 activity[J]. Bioorg. Med. Chem. Lett.,2015,25(6):1 232-1 235.
[7]ISHIDA J,WANG H K,BASTOW K F,et al.Antitumor agents 201.1,cytotoxicity of harmine andβ-carboline analogs[J]. Bioorg. Med. Chem. Lett.,1999,9(23):3 319-3 324.
[8]BARSANTI P A,WANG W,NI Z J,et al.The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5[J].Bioorg.Med.Chem.Lett.,2010,20(1):157-160.
[9]LIU L,MA Y Y,WANG K,et al.Anti-tumor and antimicrobial activities ofβ-carbolines[J]. Chem. J. Chinese U.,2018,39(4):674-680.
[10]周鑫鑫,周宁,刘长春.单取代/双取代氧化吲哚衍生物的合成研究[J].化学试剂,2018,40(1):97-102.
[11]MULCAHY S P,VARELAS J G.Three-step synthesis of an annulatedβ-carboline via palladium catalysis[J].Cheminform,2013,54(48):6 599-6 601.
[12]SUDHAKAR M,SADHANA S,ABUBAKAR W,et al.Discovery of a marine-derived bis-indole alkaloid fascaplysin,as a newclass of potent P-glycoprotein inducer and establishment of its structure eactivity relationship[J].Eur.J.Med.Chem.,2016,107(1):1-11.
[13]MEESALA R,ARSHAD A S M,MORDI M N,et al.Iodine-catalyzed one-pot decarboxylative aromatization of tetrahydro-β-carbolines[J].Tetrahedron,2016,72(52):8 537-8 541.
[14]DONG J,SHI X X,YAN J J,et al.Efficient and practical one-pot conversions of N-tosyltetrahydroisoquinolines into isoquinolines and of N-tosyltetrahydro-β-carbolines intoβ-carbolines through tandemβ-elimination and aromatization[J]. Eur. J. Org. Chem.,2010,2 010(36):6 987-6 992.
[15]TADA M,SAEKI H,OIKAWA A.The identification of 3-amino-9H-pyrido[3,4-b]indole derivatives in L-tryptophan pyrolysates[J].Bull.Chem.Soc.Jpn.,1983,56(5):1 450-1 554.
[16]GUO L,CAO R H,FAN W X,et al. Design,synthesis and in vitro antitumor activities of novel bivalentβ-carbolines[J]. Chem. J. Chinese U.,2005,40(10):991-1 001.
[17]GUO L,FAN W X,GAN Z Y,et al.Design and synthesis of 1-substituted-β-carboline derivatives as potential anticancer agents[J]. Chin. Pharm.,2015,26(14):1 869-1 885.
[18]ZENI G,LAROCK R C. Synthesis of heterocycles via palladiumπ-olefin andπ-alkyne chemistry[J]. Chem.Rev.,2004,104(5):2 285-2 309.
[19]SONG Y C,WANG J,DENG Y,et al.β-Carbolines as specific inhibitors of cyclin-dependent kinases[J].Med.Chem.Lett.,2002,12(7):1 129-1 132.
[20]WANG Z X,XIANG J C,CHENG Y,et al.Direct biomimetic synthesis ofβ-carboline alkaloids from two amino acids[J].J.Org.Chem.,2018,83(19):12 247-12 254.
[21]IVANOV I,NIKOLOVA S,STAKOVA-ABEGHE S. A simple method for the synthesis of 1-substitutedβ-carboline derivatives from tryptamine and carboxylic acids in polyphosphoric acid[J]. Heterocycles,2005,65(10):2 483-2 492.
[22]GILSON Z,RICHARD C L.Synthesis of heterocycles via palladium-catalyzed oxidative addition[J]. Chem. Rev.,2006,106(11):4 644-4 680.