一锅法合成含氨基葡萄糖分子片段的2-硫代喹唑啉二酮衍生物
|
摘要
以1,3,4,6-四-O-苄基-β-D-氨基葡萄糖盐酸盐(1),2-硫代喹唑啉二酮(2a~2g)和固体光气为原料,采用一锅法合成了7个含氨基葡萄糖分子片段的2-硫代喹唑啉二酮衍生物(3a~3g),其结构经1H NMR,FT-IR和HR-ESI-MS确证。在最佳反应条件[1,2-二氯乙烷为溶剂,三乙胺为碱,1 3mmol,n(1)∶n(2b)=1.0∶1.1,回流反应8 h]下,3b收率82%。
Seven 2-thioquinazolinedione derivatives(3a ~ 3g) containing glucosamine molecular fragments were synthesized by one-pot method using 1,3,4,6-tetra-O-benzyl-β-D-glucosamine hydrochloride(1),2-thioxoquinazolinediones(2a ~ 2g) and solid phosgene as the materials.The structures were confirmed by1 H NMR,FT-IR and HR-ESI-MS.Under the optimum reaction conditions[1,2-dichloroethane as the solvent,triethylamine as the alkali,1 3 mmol,n(1) ∶ n(2b)=1.0 ∶ 1.1,reflux for 8 h],the yield of 3b was 82%.
Seven 2-thioquinazolinedione derivatives(3a ~ 3g) containing glucosamine molecular fragments were synthesized by one-pot method using 1,3,4,6-tetra-O-benzyl-β-D-glucosamine hydrochloride(1),2-thioxoquinazolinediones(2a ~ 2g) and solid phosgene as the materials.The structures were confirmed by1 H NMR,FT-IR and HR-ESI-MS.Under the optimum reaction conditions[1,2-dichloroethane as the solvent,triethylamine as the alkali,1 3 mmol,n(1) ∶ n(2b)=1.0 ∶ 1.1,reflux for 8 h],the yield of 3b was 82%.
引文
[1]Mhaske S B,Argade N P.The chemistry of recently isolated naturally occurring quinazolinone alkaloids[J].Tetrahedron,2006,62(42):9787-9826.
[2]Wissner A,Overbeek E,Reich M F,et al.Synthesis and structure-activity relationships of 6,7-disubstituted4-anilinoquinoline-3-carbonitriles.The design of a n orally active,irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor-2(HER-2)[J].Journal of Medicinal Chemistry,2003,46(1):49-63.
[3]Jatav V,Mishra P,Kashaw S,et al.Synthesis and CNS depressant activity of some novel 3-(5-substituted1,3,4-thiadiazole-2-yl)-2-styryl quinazoline-4-(3H)-ones[J].European Journal of Medicinal Chemistry,2008,43(1):135-141.
[4]Liu L T,Yuan T T,Liu H H,et al.Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors[J].Bioorganic&Medicinal Mhemistry Letters,2007,17(22):6373-6377.
[5]Liu G,Hu D Y,Jin L H,et al.Synthesis and bioactivities of 6,7,8-trimethoxy-N-aryl-4-aminoquinazoline derivatives[J].Bioorganic&Medicinal Chemistry,2007,15(20):6608-6617.
[6]Marsham P R,Hughes L R,Jackman A L,et al.Quinazoline antifolate thymidylate synthase inhibitors:Heterocyclic benzoyl ring modifications[J].Journal of Medicinal Chemistry,1991,34(5):1594-1605.
[7]Xu G F,Song B A,Bhadury P S,et al.Synthesis and antifungal activity of novel s-substituted 6-fluoro-4-alkyl(aryl)thioquinazoline derivatives[J].Bioorganic&Medicinal Chemistry,2007,15(11):3768-3774.
[8]高兴文,蔡学建,严凯,等.4(3H)-喹唑啉酮类Schiff碱的合成与抗烟草花叶病毒活性[J].有机化学,2008,28(10):1785-1791.
[9]丁明武,杨尚君,陈云峰.2-烷氧基-3H-喹唑啉-4-酮的合成与杀菌活性[J].有机化学,2004,24(8):923-926.
[10]陈舒忆,吕同杰,严和平,等.喹唑啉类衍生物的合成及其抗肿瘤活性[J].合成化学,2013,21(1):92-95.
[11]鲍小平,刘军虎,张峰,等.含1,2,4-三唑硫醚单元的新型喹唑啉酮类衍生物的合成及其抗菌活性[J].合成化学,2013,21(2):200-203.
[12]Ghosh S,Blumenthal H J,Davidson E,et al.Glucosamine metabolism V.Enzymatic synthesis of glucosamine 6-phosphate[J].Journal of Biological Chemistry,1960,235(5):1265-1273.
[13]Quastel J H.Inhibition of tumour growth by D-glucosamine[J].Nature,1953,171:252-254.
[14]Nagaoka I,Igarashi M,Hua J,et al.Recent aspects of the anti-inflammatory actions of glucosamine[J].Carbohydrate Polymers,2011,84(2):825-830.
[15]Aly M R E,Schmidt R R.New diacylamino protecting groups for glucosamine[J].European Journal of Organic Chemistry,2005,20:4382-4392.
[16]刘玮炜,张强,霍云峰,等.微波一锅法合成2-硫代喹唑啉二酮衍生物[J].化学试剂,2014,36(4):367-369.
[2]Wissner A,Overbeek E,Reich M F,et al.Synthesis and structure-activity relationships of 6,7-disubstituted4-anilinoquinoline-3-carbonitriles.The design of a n orally active,irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor(EGFR)and the human epidermal growth factor receptor-2(HER-2)[J].Journal of Medicinal Chemistry,2003,46(1):49-63.
[3]Jatav V,Mishra P,Kashaw S,et al.Synthesis and CNS depressant activity of some novel 3-(5-substituted1,3,4-thiadiazole-2-yl)-2-styryl quinazoline-4-(3H)-ones[J].European Journal of Medicinal Chemistry,2008,43(1):135-141.
[4]Liu L T,Yuan T T,Liu H H,et al.Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors[J].Bioorganic&Medicinal Mhemistry Letters,2007,17(22):6373-6377.
[5]Liu G,Hu D Y,Jin L H,et al.Synthesis and bioactivities of 6,7,8-trimethoxy-N-aryl-4-aminoquinazoline derivatives[J].Bioorganic&Medicinal Chemistry,2007,15(20):6608-6617.
[6]Marsham P R,Hughes L R,Jackman A L,et al.Quinazoline antifolate thymidylate synthase inhibitors:Heterocyclic benzoyl ring modifications[J].Journal of Medicinal Chemistry,1991,34(5):1594-1605.
[7]Xu G F,Song B A,Bhadury P S,et al.Synthesis and antifungal activity of novel s-substituted 6-fluoro-4-alkyl(aryl)thioquinazoline derivatives[J].Bioorganic&Medicinal Chemistry,2007,15(11):3768-3774.
[8]高兴文,蔡学建,严凯,等.4(3H)-喹唑啉酮类Schiff碱的合成与抗烟草花叶病毒活性[J].有机化学,2008,28(10):1785-1791.
[9]丁明武,杨尚君,陈云峰.2-烷氧基-3H-喹唑啉-4-酮的合成与杀菌活性[J].有机化学,2004,24(8):923-926.
[10]陈舒忆,吕同杰,严和平,等.喹唑啉类衍生物的合成及其抗肿瘤活性[J].合成化学,2013,21(1):92-95.
[11]鲍小平,刘军虎,张峰,等.含1,2,4-三唑硫醚单元的新型喹唑啉酮类衍生物的合成及其抗菌活性[J].合成化学,2013,21(2):200-203.
[12]Ghosh S,Blumenthal H J,Davidson E,et al.Glucosamine metabolism V.Enzymatic synthesis of glucosamine 6-phosphate[J].Journal of Biological Chemistry,1960,235(5):1265-1273.
[13]Quastel J H.Inhibition of tumour growth by D-glucosamine[J].Nature,1953,171:252-254.
[14]Nagaoka I,Igarashi M,Hua J,et al.Recent aspects of the anti-inflammatory actions of glucosamine[J].Carbohydrate Polymers,2011,84(2):825-830.
[15]Aly M R E,Schmidt R R.New diacylamino protecting groups for glucosamine[J].European Journal of Organic Chemistry,2005,20:4382-4392.
[16]刘玮炜,张强,霍云峰,等.微波一锅法合成2-硫代喹唑啉二酮衍生物[J].化学试剂,2014,36(4):367-369.