应用Pictet-Spengler关环反应合成吡啶并[3，2-e]吡咯并[1，2-a]吡嗪类化合物及其类似物
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摘要
本文论述了Pictet-Spengler类关环反应在设计、合成吡啶并[3,2-e]吡咯并[1,2-a]吡嗪类化合物及其类似物中的应用,总共分为三章。
第一章综述了吡啶并环化合物的生物活性以及吡啶并吡嗪及其类似物的生物活性,同时也总结了此类化合物的合成方法。接下来介绍了Pictet-Spengler关环反应在有机合成以及药物化学中的研究进展。
第二章中,通过对2-氨基-3-硝基-6-氯吡啶衍生物与醛或酮之间的Pictet- Spengler类关环反应的研究,开发了合成吡啶并[3,2-e]吡咯并[1,2-a]吡嗪类化合物分子构架的方法,并对2-氯-吡啶并[3,2-e]吡咯并[1,2-a]吡嗪中的氯原子进行衍生化反应,为杂环化合物库的建立打下了基础。
第三章中,利用Pictet-Spengler类反应合成出吡啶并[2,3-e]吡咯并[1,2-a]吡嗪类化合物,接着又考查了氯原子的反应活性。开发出了一条可行的合成吡啶并[2,3-e]吡咯并[1,2-a]吡嗪类化合物的方法。
Pyridine-fused heterocyclic scaffolds show many biological activities. Several drugs containing sub-pyridine structure have been on the market. Quinolone is one typical example of pyridine-fused heterocyclic scaffolds. Many pyridine-fused heterocyclic scaffolds also exhibit biological activities.Pyrrole-fused pyrazine and its similar structures also have many many biological activities. The activities mainly focus on potent 5-HT receptor agonists and anti HIV virus. Basing on the summary, we find that the methods of synthesizing this kind of compounds are very limited. So it is very important to develop new methods to fulfill the needs. The aim of the dissertation was to design and synthesize Pyridine[3, 2-e]pyrrolo[1, 2-a]pyrazines and analogues via Pictet-Spengler-type cyclization reaction.
Basing on the former research in our laboratory, an efficient method was developed for the construction of Pyridine[3, 2-e]pyrrolo[1, 2-a]pyrazines and analogues. 2-amino-3-nitro-6-chloro-pyridne was our starting material. It is commercially available, and very inexpensive. 2-(1H-pyrrole-1-yl)-3-amino-6-chloro -pyridine was prepared by two step process from the starting material. The first step was Clauson-Kass reaction, and the second step was reduction of nitro group. The cyclization reactions of 2-(1H-pyrrole-1-yl)-3-amino-6-chloro-pyridine with various aldehydes and ketons were conducted under the condition that trifluoroacetic acid and the acetonitrile refluxing. After that, we also study the reaction activity of 2-cholo, we can build chemical compounds library through that.
In order to increasing the diversity of the compounds and saving money, we still use 2-amino-3-nitro-6-chloro-pyridne as our starting material. After reduction of nitro and Clauson-Kass reactions, we get the intermediate– pyridine 2-amino-3-(1H-pyrrol e-1-yl)- 6-chloro-pyridine. We still use the former method to cyclization. After the cyclization, we can still synthesize the similar compounds through 2-cholo.
第一章综述了吡啶并环化合物的生物活性以及吡啶并吡嗪及其类似物的生物活性,同时也总结了此类化合物的合成方法。接下来介绍了Pictet-Spengler关环反应在有机合成以及药物化学中的研究进展。
第二章中,通过对2-氨基-3-硝基-6-氯吡啶衍生物与醛或酮之间的Pictet- Spengler类关环反应的研究,开发了合成吡啶并[3,2-e]吡咯并[1,2-a]吡嗪类化合物分子构架的方法,并对2-氯-吡啶并[3,2-e]吡咯并[1,2-a]吡嗪中的氯原子进行衍生化反应,为杂环化合物库的建立打下了基础。
第三章中,利用Pictet-Spengler类反应合成出吡啶并[2,3-e]吡咯并[1,2-a]吡嗪类化合物,接着又考查了氯原子的反应活性。开发出了一条可行的合成吡啶并[2,3-e]吡咯并[1,2-a]吡嗪类化合物的方法。
Pyridine-fused heterocyclic scaffolds show many biological activities. Several drugs containing sub-pyridine structure have been on the market. Quinolone is one typical example of pyridine-fused heterocyclic scaffolds. Many pyridine-fused heterocyclic scaffolds also exhibit biological activities.Pyrrole-fused pyrazine and its similar structures also have many many biological activities. The activities mainly focus on potent 5-HT receptor agonists and anti HIV virus. Basing on the summary, we find that the methods of synthesizing this kind of compounds are very limited. So it is very important to develop new methods to fulfill the needs. The aim of the dissertation was to design and synthesize Pyridine[3, 2-e]pyrrolo[1, 2-a]pyrazines and analogues via Pictet-Spengler-type cyclization reaction.
Basing on the former research in our laboratory, an efficient method was developed for the construction of Pyridine[3, 2-e]pyrrolo[1, 2-a]pyrazines and analogues. 2-amino-3-nitro-6-chloro-pyridne was our starting material. It is commercially available, and very inexpensive. 2-(1H-pyrrole-1-yl)-3-amino-6-chloro -pyridine was prepared by two step process from the starting material. The first step was Clauson-Kass reaction, and the second step was reduction of nitro group. The cyclization reactions of 2-(1H-pyrrole-1-yl)-3-amino-6-chloro-pyridine with various aldehydes and ketons were conducted under the condition that trifluoroacetic acid and the acetonitrile refluxing. After that, we also study the reaction activity of 2-cholo, we can build chemical compounds library through that.
In order to increasing the diversity of the compounds and saving money, we still use 2-amino-3-nitro-6-chloro-pyridne as our starting material. After reduction of nitro and Clauson-Kass reactions, we get the intermediate– pyridine 2-amino-3-(1H-pyrrol e-1-yl)- 6-chloro-pyridine. We still use the former method to cyclization. After the cyclization, we can still synthesize the similar compounds through 2-cholo.
引文
[1] JOHNSON D S, LI J. The Art of Drug Synthesis [M].华东理工大学出版社, 2008.
[2] SCOTTH A, BRIANA J, KRISTJANS, et al. Synthesis of C-6substituted pyrazolo[1,5-a]pyridines with potent activity against herpesviruses [J]. Bioorg Med Chem, 2006, 14, 944-954.
[3] BERNARDINO A M R, PINHEIRO L C, RODRIGUES C R, et al. Design synthesis SAR and biological evaluation of new 4-(phenylamino)thieno[2,3-b]pyr idine derivatives [J]. Bioorg Med Chem, 2006, 14, 5765–5770.
[4] VERON J-B, ENGUEHARD-GUEIER C, SNOECK R, et al. Influence of 6 or 8-substitution on the antiviral activity of 3-phenethyl thiomethyl imidazo[1,2-a]pyridine against human cytomegalovirus (HCMV)and varicella-zostervirus(VZV) [J]. Bioorg Med Chem, 2007, 15:7209–7219.
[5] DIAS L R.S, B.SANTOS M, ALBUQUERQUE S D, et al. Synthesis in vitro evaluation and SAR studies of apotential antichagasic 1H-pyrazolo[3,4-b]pyridineseries [J]. Bioorg Med Chem, 2007, 15: 211–219.
[6] PALMER A M , CHRISMANN S, MUNCH G, et al. Spiro(imidazo[1,2-a]pyrano [2,3-c]pyridine-9-indenes) asinhibitors of gastricacid secretion [J]. Bioorg Med Chem, 2009, 17: 368-384.
[7] PALMER A M, MUNCH G, BREHM C, et al. 5-Substituted1H- pyrrolo[3,2-b]pyridines as inhibitors of gastricacidsecretion [J]. Bioorg Med Chem, 2008, 16: 1511–1530.
[8] B.BHARATE S, MAHAJAN T R, GOLE Y R, et al. Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural naloguesasTNF-a andIL-6 inhibitors [J]. Bioorg Med Chem, 2008, 16: 7167–7176.
[9] S.GIRGIS A, MISHRIKY N, ELLITHEY M, et al. Novel synthesis of
[1]-benzothiepino[5,4-b]pyridine-3-carbonitriles andtheira nti-infla mmatory properties [J]. Bioorg Med Chem, 2007, 15: 2403–2413.
[10] ELOKDAH H, LI D, MCFARLANE G, et al. Novel 1-(azacyclyl) - 3- aryl sulf onyl-1H-pyrrolo[2,3-b]pyridines as 5-HT6 agonists and antagonists [J]. Bioorg Med Chem, 2007, 15: 6208–6226.
[11] BUTINI S, BUDRIESI R, HAMON M, et al. Novel,Potent,and Selective Quinoxaline-Based5-HT Receptor Ligands.1.Further Structure-Activity Relationships and Pharmacological Characterization [J]. J Med Chem, 2009, 52 6946-6950.
[12] BAHEKAR R H, JAIN M R, JADAV P A, et al. Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines [J]. Bioorganic&MedicinalChemistry, 2007, 15: 6782–6795.
[13] LEAL B , AFONSO I F , RODRIGUES C R , et al. Antibacterial profile against drug-resistant Staphylococcus epidermidis clinical strainand structure–activity relationship studies of 1H-pyrazolo[3,4-b]pyridine and thieno[2,3-b]pyridine derivatives [J]. Bioorg Med Chem Lett, 2008, 16: 8196–8204.
[14] MICHELIB F, REABOZZOLI, CRIPPA L, CAVANNI P, FABIOD R D, MERLO G, PAIO A, PERUGINI L, ZARANTONELLO P. Phenylethynyl -pyrrolo[1,2-a]pyrazine: Anewpotent and selective tool in the mGluR5 antagonists arena [J]. Bioorg Med Chem Lett, 2008, 18: 1804-1809.
[15] MICHELI F, BERTANI B, BOZZOLI A, et al. Phenylethynyl- pyrrolo [1,2-a] pyrazine:A new potent and selective tool in the mglur5 antagonists arena. [J]. Bioorg Med Chem lett, 2008, 18: 1804-1809.
[16] BROWN A, HENDERSON A, LANE C, et al. Small molecule inhibitors of IgE synthesis [J]. Bioorg Med Chem lett, 2006, 16: 4697-4699.
[17] MULVIHILL M J, JI Q-L, WERNER D, et al. 1,3-Disubstituted-imidazo [1,5-a] pyrazines as insulin-like growth-factor-Ireceptor (IGF-IR) inhibitors. [J]. Bioorg Med Chem lett, 2007, 17:1091-1097.
[18] ZIMMERMANN P J, BREHM C, BUHR W, et al. Novel imidzao[1,2-a]pyrazine derivatives as potent reversible inhibitors of the gastric H+/K+-ATPase. [J]. Bioorg Med Chem, 2008, 16: 536-541.
[19] RAULT S, LANCELOT J-C, PRUNIER H, et al. Novel Selective and Partial Agonists of 5-HT Receptors.Part1. Synthesis and Biological Evaluation of Piperazinopyrrolothienopyrazines [J]. J Med Chem, 1996, 39: 2068-2080.
[20] CAMPIANI G, CAPPELLI A, NACCI V, et al. Novel and Highly Potent 5-HT Receptor Agonists Based on a Pyrroloquinoxaline Structure [J]. J Med Chem, 1997, 40: 3670-3678.
[21] CAMPIANI G, MORELLI E, GEMMA S, et al. Pyrroloquinoxaline Derivativesas High-Affinity and Selective 5-HT Receptor Agonists:Synthesis, Further Structure Activity Relationships, and Biological Studies [J]. J Med Chem, 1999, 42: 4362-4379.
[22] CONTOUR-GALCERA M-O, POITOUT L, MOINET C, et al. Synthesis of Substituted Imidazopyrazines as Ligands for the Human Somatostatin Receptor Subtype5. [J]. Bioorg Med Chem lett, 2001, 11: 741-745.
[23] KUNDU B, SAWANT D, CHHABRA R. A Modified Strategy for PictetSpengler Reaction Leading to the Synthesis of Imidazo quinoxalines on Solid Phase [J]. J Comb Chem, 2005, 7 317-321.
[24]黄培强.有机人名反应、试剂与规则[M].化学工业出版社, 2008.
[25] SEAYAD J, SEAYAD A M, LIST B. Catalytic Asymmetric Pictet Spengler Reaction [J]. J AM CHEM SOC, 2006, 128 1086-1087.
[26] KOLSHORN H, MEIER H, Abonia R, Insuasty B, Quirga J. A Versatile Synthesis of 4.5-Dihydropyrrolo[1,2-a]quinoxalines [J]. J Heterocyclic Chem, 2001, 38 671-674.
[27] KUNDU B, SAWANT D, PARTANI P, et al. New application of Pictet-Spengler Reaction Leading to the Synthesis of an Unusual Seven-Membered Heterocyclic Ring System [J]. J Org Chem, 2005, 70 4889-4892.
[28] SHARMA S, KUNDU B. Application of the Modified Pictet-Spengler Cyclization Reaction for the Preparation of anImidazopyrazine Ring:Synthesis of new Pyrido-and Pyrimido-imidazopyrazines [J]. J Comb Chem 2009, 11 720–731.
[29] SHARMA S, SAHA B, SAWANT D, et al. Synthesis of Novel N-RichPolycyclic Skeletons Based on Azoles and Pyridines [J]. J Comb Chem, 2007,9:783-792.
[30] AGARWAL P K, SHARMA S K, SAWANT D, et al. Application of the Pictet–Spengler reaction to arylamine-based substrates having pyrimidine as ap-ucleophile:synthesis of pyrimido quinolines with structural qanalogy to benzonaphthyridines present in alkaloids [J]. Tetrahedron, 2009, 65 1153-1161.
[31] DUNCTON M A J, SmithII L M, BURDZOVIC-WIZEMAN S, et al. Preparation of Substituted Pyrimido[4.5-b]-1.4-benzoxazepines,Thiazepines and Diazepines via a Pictet-Spengler cyclization [J]. J Org Chem, 2005, 70 9629-9631.
[32] ZHENG L, XIANG J, DANG Q, et al. Novel Heterocyclic Scaffold Consisting of Indole-Fused Pteridines [J]. J Comb Chem 2005, 7 813-815.
[33]郑连友,党群,郭四根, et al.新型1,6-二取代-5,6-二氢吡咯并[1,2-f]蝶啶衍生物的合成[J].高等学校化学学报, 2006, 27,1869-1872.
[34] XIANG J , ZHENG L, CHEN F, et al. A Cascade Reaction Consisting of Pictet-Spengler-Type Cyclization and Smiles Rearrangement: Application to the Synthesis of Novel Pyrrole-Fused Dihydropteridines [J]. Org Lett, 2007, 9, 765-767.
[35] ZHENG L, XIANG J, DANG Q, et al. Design and Synthesis of a Tetracyclic Pyrimidine-Fused Benzodiazepine Library [J]. J Comb Chem, 2006, 8, 381-387.
[36] CHE X, ZHENG L Y, DANG Q, et al. Synthesis of novel tricyclic pyrimidine-fused5,6-dihydrobenzodiazepines via a Pictet–Spengler-like cyclization [J]. Tetrahedron, 2006, 62, 2563–2568.
[37]车鑫. Pictet-Spengler类关环反应在新型嘧啶并环分子构架设计与合成中的应用[D];吉林大学, 2008.
[38] SHI F, XU X, ZHENG L, et al. Method Development for a Pyridobenzodiazepine Librarywith Multiple Diversification Points [J]. J Comb Chem, 2008, 10, 158–161. 48
[2] SCOTTH A, BRIANA J, KRISTJANS, et al. Synthesis of C-6substituted pyrazolo[1,5-a]pyridines with potent activity against herpesviruses [J]. Bioorg Med Chem, 2006, 14, 944-954.
[3] BERNARDINO A M R, PINHEIRO L C, RODRIGUES C R, et al. Design synthesis SAR and biological evaluation of new 4-(phenylamino)thieno[2,3-b]pyr idine derivatives [J]. Bioorg Med Chem, 2006, 14, 5765–5770.
[4] VERON J-B, ENGUEHARD-GUEIER C, SNOECK R, et al. Influence of 6 or 8-substitution on the antiviral activity of 3-phenethyl thiomethyl imidazo[1,2-a]pyridine against human cytomegalovirus (HCMV)and varicella-zostervirus(VZV) [J]. Bioorg Med Chem, 2007, 15:7209–7219.
[5] DIAS L R.S, B.SANTOS M, ALBUQUERQUE S D, et al. Synthesis in vitro evaluation and SAR studies of apotential antichagasic 1H-pyrazolo[3,4-b]pyridineseries [J]. Bioorg Med Chem, 2007, 15: 211–219.
[6] PALMER A M , CHRISMANN S, MUNCH G, et al. Spiro(imidazo[1,2-a]pyrano [2,3-c]pyridine-9-indenes) asinhibitors of gastricacid secretion [J]. Bioorg Med Chem, 2009, 17: 368-384.
[7] PALMER A M, MUNCH G, BREHM C, et al. 5-Substituted1H- pyrrolo[3,2-b]pyridines as inhibitors of gastricacidsecretion [J]. Bioorg Med Chem, 2008, 16: 1511–1530.
[8] B.BHARATE S, MAHAJAN T R, GOLE Y R, et al. Synthesis and evaluation of pyrazolo[3,4-b]pyridines and its structural naloguesasTNF-a andIL-6 inhibitors [J]. Bioorg Med Chem, 2008, 16: 7167–7176.
[9] S.GIRGIS A, MISHRIKY N, ELLITHEY M, et al. Novel synthesis of
[1]-benzothiepino[5,4-b]pyridine-3-carbonitriles andtheira nti-infla mmatory properties [J]. Bioorg Med Chem, 2007, 15: 2403–2413.
[10] ELOKDAH H, LI D, MCFARLANE G, et al. Novel 1-(azacyclyl) - 3- aryl sulf onyl-1H-pyrrolo[2,3-b]pyridines as 5-HT6 agonists and antagonists [J]. Bioorg Med Chem, 2007, 15: 6208–6226.
[11] BUTINI S, BUDRIESI R, HAMON M, et al. Novel,Potent,and Selective Quinoxaline-Based5-HT Receptor Ligands.1.Further Structure-Activity Relationships and Pharmacological Characterization [J]. J Med Chem, 2009, 52 6946-6950.
[12] BAHEKAR R H, JAIN M R, JADAV P A, et al. Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines [J]. Bioorganic&MedicinalChemistry, 2007, 15: 6782–6795.
[13] LEAL B , AFONSO I F , RODRIGUES C R , et al. Antibacterial profile against drug-resistant Staphylococcus epidermidis clinical strainand structure–activity relationship studies of 1H-pyrazolo[3,4-b]pyridine and thieno[2,3-b]pyridine derivatives [J]. Bioorg Med Chem Lett, 2008, 16: 8196–8204.
[14] MICHELIB F, REABOZZOLI, CRIPPA L, CAVANNI P, FABIOD R D, MERLO G, PAIO A, PERUGINI L, ZARANTONELLO P. Phenylethynyl -pyrrolo[1,2-a]pyrazine: Anewpotent and selective tool in the mGluR5 antagonists arena [J]. Bioorg Med Chem Lett, 2008, 18: 1804-1809.
[15] MICHELI F, BERTANI B, BOZZOLI A, et al. Phenylethynyl- pyrrolo [1,2-a] pyrazine:A new potent and selective tool in the mglur5 antagonists arena. [J]. Bioorg Med Chem lett, 2008, 18: 1804-1809.
[16] BROWN A, HENDERSON A, LANE C, et al. Small molecule inhibitors of IgE synthesis [J]. Bioorg Med Chem lett, 2006, 16: 4697-4699.
[17] MULVIHILL M J, JI Q-L, WERNER D, et al. 1,3-Disubstituted-imidazo [1,5-a] pyrazines as insulin-like growth-factor-Ireceptor (IGF-IR) inhibitors. [J]. Bioorg Med Chem lett, 2007, 17:1091-1097.
[18] ZIMMERMANN P J, BREHM C, BUHR W, et al. Novel imidzao[1,2-a]pyrazine derivatives as potent reversible inhibitors of the gastric H+/K+-ATPase. [J]. Bioorg Med Chem, 2008, 16: 536-541.
[19] RAULT S, LANCELOT J-C, PRUNIER H, et al. Novel Selective and Partial Agonists of 5-HT Receptors.Part1. Synthesis and Biological Evaluation of Piperazinopyrrolothienopyrazines [J]. J Med Chem, 1996, 39: 2068-2080.
[20] CAMPIANI G, CAPPELLI A, NACCI V, et al. Novel and Highly Potent 5-HT Receptor Agonists Based on a Pyrroloquinoxaline Structure [J]. J Med Chem, 1997, 40: 3670-3678.
[21] CAMPIANI G, MORELLI E, GEMMA S, et al. Pyrroloquinoxaline Derivativesas High-Affinity and Selective 5-HT Receptor Agonists:Synthesis, Further Structure Activity Relationships, and Biological Studies [J]. J Med Chem, 1999, 42: 4362-4379.
[22] CONTOUR-GALCERA M-O, POITOUT L, MOINET C, et al. Synthesis of Substituted Imidazopyrazines as Ligands for the Human Somatostatin Receptor Subtype5. [J]. Bioorg Med Chem lett, 2001, 11: 741-745.
[23] KUNDU B, SAWANT D, CHHABRA R. A Modified Strategy for PictetSpengler Reaction Leading to the Synthesis of Imidazo quinoxalines on Solid Phase [J]. J Comb Chem, 2005, 7 317-321.
[24]黄培强.有机人名反应、试剂与规则[M].化学工业出版社, 2008.
[25] SEAYAD J, SEAYAD A M, LIST B. Catalytic Asymmetric Pictet Spengler Reaction [J]. J AM CHEM SOC, 2006, 128 1086-1087.
[26] KOLSHORN H, MEIER H, Abonia R, Insuasty B, Quirga J. A Versatile Synthesis of 4.5-Dihydropyrrolo[1,2-a]quinoxalines [J]. J Heterocyclic Chem, 2001, 38 671-674.
[27] KUNDU B, SAWANT D, PARTANI P, et al. New application of Pictet-Spengler Reaction Leading to the Synthesis of an Unusual Seven-Membered Heterocyclic Ring System [J]. J Org Chem, 2005, 70 4889-4892.
[28] SHARMA S, KUNDU B. Application of the Modified Pictet-Spengler Cyclization Reaction for the Preparation of anImidazopyrazine Ring:Synthesis of new Pyrido-and Pyrimido-imidazopyrazines [J]. J Comb Chem 2009, 11 720–731.
[29] SHARMA S, SAHA B, SAWANT D, et al. Synthesis of Novel N-RichPolycyclic Skeletons Based on Azoles and Pyridines [J]. J Comb Chem, 2007,9:783-792.
[30] AGARWAL P K, SHARMA S K, SAWANT D, et al. Application of the Pictet–Spengler reaction to arylamine-based substrates having pyrimidine as ap-ucleophile:synthesis of pyrimido quinolines with structural qanalogy to benzonaphthyridines present in alkaloids [J]. Tetrahedron, 2009, 65 1153-1161.
[31] DUNCTON M A J, SmithII L M, BURDZOVIC-WIZEMAN S, et al. Preparation of Substituted Pyrimido[4.5-b]-1.4-benzoxazepines,Thiazepines and Diazepines via a Pictet-Spengler cyclization [J]. J Org Chem, 2005, 70 9629-9631.
[32] ZHENG L, XIANG J, DANG Q, et al. Novel Heterocyclic Scaffold Consisting of Indole-Fused Pteridines [J]. J Comb Chem 2005, 7 813-815.
[33]郑连友,党群,郭四根, et al.新型1,6-二取代-5,6-二氢吡咯并[1,2-f]蝶啶衍生物的合成[J].高等学校化学学报, 2006, 27,1869-1872.
[34] XIANG J , ZHENG L, CHEN F, et al. A Cascade Reaction Consisting of Pictet-Spengler-Type Cyclization and Smiles Rearrangement: Application to the Synthesis of Novel Pyrrole-Fused Dihydropteridines [J]. Org Lett, 2007, 9, 765-767.
[35] ZHENG L, XIANG J, DANG Q, et al. Design and Synthesis of a Tetracyclic Pyrimidine-Fused Benzodiazepine Library [J]. J Comb Chem, 2006, 8, 381-387.
[36] CHE X, ZHENG L Y, DANG Q, et al. Synthesis of novel tricyclic pyrimidine-fused5,6-dihydrobenzodiazepines via a Pictet–Spengler-like cyclization [J]. Tetrahedron, 2006, 62, 2563–2568.
[37]车鑫. Pictet-Spengler类关环反应在新型嘧啶并环分子构架设计与合成中的应用[D];吉林大学, 2008.
[38] SHI F, XU X, ZHENG L, et al. Method Development for a Pyridobenzodiazepine Librarywith Multiple Diversification Points [J]. J Comb Chem, 2008, 10, 158–161. 48