刺五加皂甙对自由基作用和无血清培养条件下两种神经元衰老模型细胞的保护作用

目的：对体外小鼠胎鼠皮质神经元采用自由基作用和无血清培养条件建立衰老模型，观察刺五加皂甙对衰老神经元的保护作用。方法：实验于2000-05／11在南通大学航海医学研究所生化教研室完成。选择孕15～17d的小鼠胎鼠，在无菌条件下，分离大脑皮质，进行原代细胞培养。自由基作用建立神经元衰老模型：①模型组：H2O2和FeS04加入到被培养7d的神经细胞内。②刺五加皂甙组：在H2O2和FeSO4处理前后24h加入12．5，25，50mg／L的刺五加皂甙。③正常对照组：不加FeSO4和H2O2及刺五加皂甙。无血清培养建立神经元衰老模型：①模型组：加入无血清的L15培养基。②刺五加皂甙组：从无血清培养前24h和无血清培养过程中分别加入12．5，25，50mg／L的刺五加皂甙。③正常对照组：在无血清处理前测各项指标。观察刺五加皂甙对两种衰老条件下的神经元存活率，乳酸脱氢酶活性，超氧化物歧化酶活性和丙二醛含量的影响。并在光镜和电镜下观察神经细胞形态。结果：自由基作用条件下：①神经细胞的存活率：12．5, 25, 50mg／L刺五加皂甙组高于模型组。②乳酸脱氢酶活性和丙二醛含量：12．5, 25, 50mg／L刺五加皂甙组均低于模型组[（0．542&;#177;0．020），（0.505&;#177;0.022），（0.502&;#177;0.076），（0．613&;#177;0．063） μkat；（10．20&;#177;0．51），（9．17&;#177;0．9），（8．95&;#177;1．72），（11．46&;#177;1．23） μmol／g，P〈0．05～0．01]。③超氧化物歧化酶活性：12．5，25，50mg／L刺五加皂甙组明显高于模型组[（32．91&;#177;1．71），（32．91&;#177;1．71），（36．10&;#177;5．37），（30．37&;#177;1．83）NU／mg，（P〈0．05-0．01）]。无血清培养条件下：①神经细胞的存活率：12．5，25，50mg／L刺五加皂甙组高于模型组。②乳酸脱氢酶活性和丙二醛含量：12．5，25，50mg／L刺五加皂甙组均低于模型组[（0．333&;#177;0．018）。（0．302&;#177;0．027），（0．309&;#177;0．064），（0．385&;#177;0．044） μkat；（7．07&;#177;0．18）。（6．33&;#177;0．48）．（6．64&;#177;1．58），（8．38&;#177;1．02） μmol／g，P〈0．05-0．01]。③超氧化物歧化酶活性：12．5，25，50mg／L刺五加皂甙组明显高于模型组[（33．98&;#177;1．52），（37．85&;#177;9．71），（38．40&;#177;6.29），（31.23&;#177;2．07）NU／mg，P〈0．05-0.01]。显微镜及扫描电镜观察，加用刺五加皂甙保护的神经细胞损伤明显减轻。部分细胞形态基本趋于正常。结论：刺五加皂甙通过降低脂质过氧化物含量，增加自由基清除力；增强细胞膜稳定性，提高皮质神经元的存活率来发挥对神经元的保护作用，改善其功能，从而延缓了神经细胞的衰老。形态学变化也表明刺五加皂甙能明显减轻衰老神经元细胞的损伤，减缓其衰老。     

党参总皂苷抗缺氧缺糖再给氧诱导大鼠皮质神经细胞凋亡的作用

目的:以原代培养的胚胎大鼠大脑皮质神经细胞进行缺氧缺糖再给氧处理,观察党参总皂苷对神经细胞凋亡的抑制作用。方法:胚胎大鼠大脑皮质神经细胞原代培养,含连二亚硫酸钠的无糖Earle's液进行缺氧缺糖处理造模,MTT法测定细胞存活率,Hoechst33342和PI原位双染法荧光显微镜观察细胞形态学变化和坏死、凋亡细胞百分率,APO-BRDU法流式细胞术检测凋亡细胞百分率,Fluo-3法流式细胞术检测细胞内Ca2+浓度,评价药效。结果:细胞存活率:与模型组犤(19.69±5.80)%犦比较党参总皂苷0.52mg/L组39.21±12.21)%,0.052mg/L组犤(犦犤(37.91±4.67)%犦能显著提高细胞存活率(P<0.001);细胞坏死率:与模型组犤(44.99±12.81)%犦比较党参总皂苷0.52mg/L组犤(15.66±4.67)%犦,0.052mg/L组犤(23.98±4.04)%犦和0.0052mg/L组犤(20.50±5.19)%犦能显著降低细胞坏死率P<0.001);原位双染法细胞凋亡(率:与模型组犤(17.44±4.82)%犦比较党参总皂苷0.52mg/L组犤(10.58±2.04)%犦,0.052mg/L组犤(11.61±2.35)%犦能显著降低细胞凋亡率(P<0.05);流式细胞术检测细胞凋亡率:与模型组犤(8.55±3.84)%犦比较党参总皂苷0.52mg/L组犤(3.85±1.92)%犦,0.0052mg/L组犤(3.45±2.22)%犦能显著降低细胞凋亡率P<0.05);(细胞内Ca2+平均荧光值,与模型组(47.     

山茱萸对衰老大鼠蛋白质非酶糖化及DNA损伤的影响

目的:研究不同剂量山茱萸醇提液对D-半乳糖致衰老大鼠体内蛋白质非酶糖化和外周血淋巴细胞DNA损伤的影响。方法:实验于2004-05/08在佳木斯动物实验中心实验室进行。41只纯系Wistar大鼠随机分为青年组(n=10)、衰老组(n=9)、山茱萸醇提液大剂量组(n=11)和小剂量组(n=11)。青年组每日上午颈背注射生理盐水60mg/kg,同时灌温开水6周;其他组每日上午60mg/kgD-半乳糖颈背注射6周制造大鼠衰老模型,大、小剂量组同时灌服5,2.5g/kg山茱萸醇提液。测定各组大鼠糖化胸主动脉、尾腱糖基化终末产物含量,应用DNA拖尾率表示外周血淋巴细胞DNA损伤,拖尾率越高,DNA损伤越重。结果:41只大鼠均进入结果分析。①衰老组大鼠尾腱、胸主动脉糖基化终未产物含量为(41.247±3.970),(25.540±3.429)AU/mg,比青年组增多犤(18.647±2.341),(12.475±2.314)AU/mg,P<0.01犦,山茱萸醇提液大剂量组犤(22.479±1.749),(16.607±1.919)AU/mg犦和小剂量组犤(29.129±4.833),(21.755±2.342)AU/mg犦均比衰老组低。②DNA拖尾率以衰老组最高,为(73.633±4.507)%,小剂量组犤(54.841±3.265)%犦和大剂量组犤(46.377±4.643)%犦比衰老组低,但高于青年组犤(39.069±3.601)%,P<0.01犦。结论:山茱萸醇提液可抑制体内蛋白质非酶糖化、减少外周血淋巴细胞DNA损伤,具有一定抗衰老作用。     

七宝美髯丹改善衰老症状的机制

目的:通过临床观察衰老症状及指数,分析七宝美髯丹延缓衰老的机制。方法:共选入l50名老年健康者,为2001-01/2004-01哈尔滨医科大学附属第一医院体检中心的老年人,随机分为治疗组100例和对照组50例,分别给予口服七宝美髯丹及安慰剂胶囊,4粒/次,3次/d,连服2个月,服药前后对衰老症状及主要指标超氧化物歧化酶、血浆过氧化脂质、血浆睾酮、雌二醇及高密度脂蛋白胆固醇等进行评定及监测。结果:参选的150人全部完成数据采集,无脱落者。①衰老症状积分变化:治疗组衰老症状积分小于对照组(13.82±3.56,21.46±3.68,P<0.01)。②临床指标变化:治疗后治疗组治疗后超氧化物歧化酶活性大于对照组,过氧化脂质含量小于对照组犤(8215.31±1445.79),(4813.63±1024.87)nkat/g;(1.59±0.32),(3.09±1.06)mmol/L,P<0.01犦;治疗组睾酮大于对照组、雌二醇/睾酮值小于对照组犤(5764.0±1202.2),(4865.6±1432.8)ng/L;(0.0566±0.0176),(0.0698±0.0296),P<0.01犦;治疗组高密度脂蛋白胆固醇值大于对照组犤(2.18±0.09),(0.94±0.08)mmol/L,P<0.01犦。结论:七宝美髯丹可减少自由基对机体损害,能提高机体抗氧化活力,可调整脂质代谢紊乱,调节体内激素水平,起到补肾壮阳、抗老防衰、延年益寿的作用。     

中药补气养阴清热活血方抗运动性疲劳的实验研究

目的:探讨中药(非禁用药物)补气养阴清热活血方对抗运动性疲劳的作用。方法:以小鼠为实验动物,分实验组灌服补气养阴清热活血液,运动对照组和正常组灌同等量的生理盐水,每组10只。检测各组小鼠游泳至力竭的时间;力竭游泳后骨骼肌超氧化物歧化酶(superoxidedismutaseSOD)、肌酸激酶、乳酸脱氢酶(lactatedehydrogenaeactivity,LDH)活性和血清肌酸激酶、血清LDH活性;力竭运动结束3h后(恢复期)的血糖浓度、肌糖原和肝糖原的含量。结果:灌服补气养阴清热活血液组小鼠2次力竭游泳时间犤分别为(38.38±6.51),(35.83±8.65)min犦较运动对照组犤分别(28.41±5.38),(23.43±6.84)min犦明显延长,差异显著性意义(t=4.72,4.86P均<0.01);实验组骨骼肌LDH犤(13.37±1.60)μkat犦,SOD犤(49.38±11.77)μkat犦、肌酸激酶(75.47±20.03)μkat犦活性和血清LDH(10.14±2.88)μkat犦,肌酸激酶(30.11±5.61)μkat犦活性较运动对照组犤分别为(1.09±1.83),(43.40±8.88),(44.75±207.14)(14.01±3.16),(91.46±16.50)μkat犦增高,差异有显著性意义(t=2.4～6.3,P均<0.01);实验组力竭游泳3h后肌糖原和肝糖原含量(mg/g)的增加犤分别为(3.91±0.84),(24.87±11.54)犦较运动对照组犤分别为(2.58±0.62),(14.34±7.34)犦明显加快,差异     

仙人掌粉对大鼠高脂血症的治疗作用

目的:探讨进食仙人掌粉对高血脂大鼠血脂水平的影响。方法:将造模成功的高血脂大鼠随机分为四组:分别为模型对照组和仙人掌粉高、中、低三剂量组,后者按高、中、低三种剂量给予样品。以上各组继续喂饲高脂饲料3周,于给样前、后分别取血测定血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇(high-densitylipoproteincholesterol,HDL-C),并且计算低密度脂蛋白胆固醇(low-densitylipoproteincholes-terol,LDL-C)、动脉硬化指数(arteriosclerosisindex,AI)等指标。结果:仙人掌粉高、中、低三剂量组均能显著降低高脂大鼠血清总胆固醇犤(4.55±1.49),(5.90±1.37),(7.25±1.48)mmol/L犦,LDL-C犤(3.03±1.36),(4.36±1.22),(5.68±1.32)mmol/L犦,AI(2.37±0.80,3.50±0.67,4.53±0.71),三酰甘油犤(0.87±0.15),(1.15±0.22),(1.32±0.23)mmol/L犦差异均有显著性意义(t=2.43～17.32,P<0.05～0.01),且其降脂作用与给药剂量有关。结论:仙人掌粉有较明显的调节血脂作用。     

脑脉通注射液对大鼠全脑缺血再灌注损伤的保护作用(英文)

背景:脑脉通注射液是治疗缺血性脑血管病的中药复方制剂,具有拮抗钙超载,调节前列素与血栓素系统的失衡状态,阻断自由基介导的脂质过氧化反应而保护大脑。目的:观察脑脉通注射液对大鼠脑组织含水量和Ca2+含量、超氧化物歧化酶活性、脂质过氧化物、6-酮-前列素1α、血栓素水平的影响,并与复方丹参注射液做比较。设计:随机对照实验。单位:成都中医药大学实验中心。材料:实验于1997-10/1998-02成都中医药大学实验中心完成。选择健康雄性Wistar大鼠72只,随机分为6组,每组12只。①正常对照组:不进行模型制备,自由饮水,常规饲养。②模型组:腹腔注射生理盐水1.67mL/kg,2次/d。③复方丹参注射液1.67mL/kg组:腹腔注射复方丹参注射液1.67mL/kg,2次/d。④脑脉通注射液3.33,1.67,0.84mL/kg组:腹腔注射脑脉通注射液3.33,1.67,0.84mL/kg,2次/d。方法:各组大鼠用药48h后,于麻醉状态下快速断头处死,立即取出脑组织,从两半球中间切开分成两份,一份在低温下制备脑组织匀浆采用放射免疫分析法待测6-酮-前列素1α和血栓素B2水平评估前列素与血栓素系统的平衡状态、采用改进的邻苯三酚自氧化法和硫代巴比妥酸比色法检测超氧化物岐化酶活性和脂质过氧化物水平评估自由基介导的脂质过氧化情况。另一份立即在电子天平上称取干、湿重,计算脑组织含水量评估脑水肿情况。采用原子吸收分光光度法检测脑组织Ca2+含量评估钙超载情况。主要观察指标:①各组大鼠脑组织含水量和Ca2+含量。②各组大鼠脑组织超氧化物歧化酶活性、脂质过氧化物含量。③各组大鼠脑组织6-酮-前列素1α和血栓素B2含量。结果:72只大鼠均进入结果分析。①各组大鼠脑组织含水量和Ca2+含量:模型组明显高于正常组犤(82.27±1.32)%,(77.24±1.36)%;(267.47±15.69),(37.55±13.23)μg/g,P<0.01犦,4个治疗组的脑组织含水量均有不同程度的减轻,脑脉通注射液3.33mL/kg组效应最强犤(78.74±1.41)%犦,复方丹参注射液1.67mL/kg组最弱犤(81.45±1.52)%犦。复方丹参注射液各组Ca2+含量均有不同程度降低,存在剂量效应依赖性,而复方丹参注射液1.67mL/kg组Ca2+含量与模型组接近犤(253.66±12.85)μg/g,P>0.05犦。②各组大鼠脑组织超氧化物歧化酶活性、脂质过氧化物含量:模型组超氧化物歧化酶活性明显低于正常组犤(86.18±3.17),(131.86±4.67)μkat/g,P<0.01犦,经过治疗后脑脉通3个剂量组的超氧化物歧化酶活性均有提高,存在剂量效应依赖性(P<0.01),脑脉通注射液3.33mL/kg组效应最强犤(119.02±4.00)μkat/g犦,复方丹参注射液1.67mL/kg组超氧化物歧化酶活性与模型组接近(P>0.05)。模型组脂质过氧化物含量高于正常组犤(52.46±3.25),(32.29±2.23)μmol/L,P<0.01犦,各治疗组的脂质过氧化物含量均显著低于模型组,而脑脉通注射液3.33,1.67,0.84mL/kg组的疗效优于复方丹参注射液1.67mL/kg组犤(35.68±2.86),(41.54±2.47),(45.71±3.14),(47.84±2.71)μmol/L,P<0.01犦。③各组大鼠脑组织6-酮-前列素1α和血栓素B2含量:模型组脑组织6-酮-前列素1α含量明显低于正常组(P<0.01),4个治疗组均能提高6-酮-前列素1α含量,脑脉通注射液3.33,1.67,0.84mL/kg组的疗效优于复方丹参注射液1.67mL/kg组犤(43.84±2.98),(35.01±4.32),(29.97±3.81),(22.89±3.64)ng/g,P<0.01犦。模型组脑组织血栓素B2含量明显高于正常组(P<0.01),经治疗后4个治疗组与模型组比较均能显著降低脑组织血栓素B2含量,且存在剂量差异,而复方丹参注射液1.67mL/kg组的效果低于脑脉通注射液3.33,1.67,0.84mL/kg组犤(40.58±1.34),(32.85±1.43),(34.31±1.39),(37.27±1.52)ng/g,P<0.01犦。结论:脑脉通注射液可减轻脑水肿、拮抗钙离子、调节血栓素和前列腺素系统失衡、提高抗氧化酶活性和抗自由基损伤作用,从而起到保护脑组织结构和功能的治疗效应,且有一定的效量关系,脑脉通注射液的效果优于复方丹参注射液。     

清宫长春丹胶囊对小鼠运动性过氧化损伤的保护作用

目的:观察清宫长春丹胶囊(长春丹)对小鼠运动性过氧化损伤的保护作用及其机制。方法:昆明种小鼠72只(雌性),随机分为正常对照组、运动过氧化损伤模型组、长春丹0.25,0.50和1.00g/kg剂量组,维生素E30mg/kg组。每组12只,连续给药14d,测定负重游泳40min后各组小鼠血清、心、脑、肝中丙二醛含量和超氧化物歧化酶(superoxidedismutase,SOD)、谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-Px)的活性。结果:①长春丹中高剂量组小鼠血清和心、肝组织中丙二醛的含量明显降低:中剂量组分别为(6.76±1.71),(47.1±11.1)和(54.3±7.9)μmol/L,高剂量组分别为(6.45±1.82),(43.5±14.5)和(52.1±9.5)μmol/L,均明显低于损伤模型组犤(9.71±3.11),(57.4±13.6)和(62.8±12.3)μmol/L犦,差异均有显著性(P<0.05)。②小鼠血清和心、肝组织中SOD的活性:长春丹中剂量组分别为(4.78±0.44),(1.70±0.35)和(22.48±3.14)nkat/L;高剂量组分别为(4.44±0.52),(1.84±0.36)和(23.12±4.04)nkat/L,均明显高于模型组(2.97±0.52),(1.32±0.30)和(18.78±2.78)nkat/L,差异有显著性(P<0.05)。③小鼠血清和心、肝组织中GSH-Px的活性:长春丹中剂量组分别为(0.58±0.14),(0.78±0.21)和(2.47±0.51)nkat/L;高剂量组分别为(0.58±0.22)     

番茄汁对D-半乳糖衰老模型大鼠海马神经元的抗衰老作用

目的:探讨番茄汁对衰老模型大鼠海马神经元的抗衰老作用。方法:采用随机数字表将30只Wistar大鼠随机分成3组,建立D-半乳糖亚急性衰老模型,采用生化、光镜和电镜等方法,观察番茄汁对衰老大鼠海马神经元的影响。结果:番茄汁组大鼠大脑丙二醛含量犤(3.41±0.36)μmol/g犦,与乳糖组犤(4.01±0.27)μmol/g犦相比显著降低(P<0.05),超氧化物歧化酶(SOD)活性犤(25.06±1.86)NU/mg犦与D-半乳糖组犤(20.63±2.52)NU/mg犦相比明显增高(P<0.01);海马神经元形态结构衰老征象明显减轻。结论:番茄汁可延缓海马神经元的衰老进程,具有一定的抗衰老作用。     

天然牛磺酸对高铅动物模型铅含量的影响

目的:探讨天然牛磺酸是否具有排铅解毒的作用。方法:①实验于2004-10/12在广西区疾病预防控制中心毒理科完成。选用SPF级Wistar纯种雄性大白鼠55只。将检疫合格大鼠按体质量分层随机分为5组:牛磺酸高、中、低3个剂量组(以纯牛磺酸计),空白对照组,模型对照组,每组11只。②实验开始后,模型对照组、受试样品各剂量组每天饮用1g/L醋酸铅水溶液造模的同时,牛磺酸高、中、低剂量组动物灌胃给予纯牛磺酸0.07,0.14,0.21mg/kg,1次/d,连续30d;空白对照组不造成高铅模型,灌胃蒸馏水,灌胃量为10mL/kg,1次/d,连续30d。于末次给予受试药品24h后。采用瞬间高压直流电550V将大鼠电昏后处死,取血,取肝脏和股骨称重后进行湿式消化,用石墨炉原子吸收分光光度计测定铅含量。③计量资料差异比较采用方差分析。结果:大白鼠55只均进入结果分析。①血铅水平:牛磺酸高、中、低剂量组均明显低于模型对照组犤(2.49±0.31),(2.54±0.27),(2.40±0.29),(3.45±0.88)μg/L,P<0.01犦;模型对照组明显高于空白对照组犤(0.38±0.18)μg/L,P<0.01犦。②肝组织铅含量:牛磺酸高、中、低剂量组均明显低于模型对照组犤(1.73±0.64),(1.51±0.16),(1.45±0.63),(2.40±0.43)μg/g,P<0.01犦;模型对照组明显高于空白对照组犤(0.45±0.10)μg/g,P<0.01犦。股骨组织铅含量:牛磺酸高、中剂量组均明显低于模型对照组犤(3.86±1.20),(3.54±0.88),(5.00±1.34)μg/g,P<0.01犦;模型对照组明显高于空白对照组犤(0.12±0.05)μg/g,P<0.01犦。结论:天然牛磺酸具有促进血铅排出,降低肝组织、股骨内铅含量的作用。     

Silylative aromatization of p-quinone methides under metal and solvent free conditions

A base-mediated silylation reaction leading to benzyl silanes has been developed. Under transition-metal and solvent free conditions, the silylation of a wide array of p-quinone methides is achieved using a Cs₂CO₃ catalyst in yields up to 96%. Carboxylation of the as-obtained organosilane with gaseous CO₂ provides a new synthetic protocol for the preparation of carboxylic acid.

A novel and efficient synthetic protocol is reported for the synthesis of benzyl silanes from readily available silylborane and p-quinone methides using 5% cesium carbonate under solvent-free conditions.     

Synthetic strategies for aryl/heterocyclic selenides and tellurides under transition-metal-catalyst free conditions

Aryl and heteroaryl selenides and tellurides are found to have broad applications in the diverse fields such as medicine, biology, materials science, pharmaceutical etc. and thus their synthesis remains a challenging field for synthetic chemists in last decade. Although a large no of methodologies have been developed based on metal catalyzed C–Se/Te coupling, a large number of researches has been focused on developing metal catalyst free protocols due to their sustainability in recent times. This review covers all the recent developments in last decade on their synthesis under metal catalyst free conditions by using different sustainable techniques e.g. greener reagents and solvents, ball milling, visible light photocatalysis, microwave, ultrasound etc.

Synthesis of aryl and heteroaryl selenides and tellurides are summerized under transition free sustainable conditions by using greener reagents and techniques such as ball milling, microwave heating, ultrasound, visible light photocatalysis etc.     

Insight into biomass feedstock on formation of biochar-bound environmentally persistent free radicals under different pyrolysis temperatures

Environmentally persistent free radicals (EPFRs) in biochars have the ability of catalytic formation of reactive oxygen species, which may pose potential oxidative stresses to eco-environment and human health. Therefore, comprehending the formation and characteristics of EPFRs in biochars is important for their further applications. In this study, the woody lignocellulosic biomass (wood chips, pine needle and barks), non-woody lignocellulosic biomass (rice husk, corn stover, and duckweed), and non-lignocellulosic biomass (anaerobically digested sludge) were selected as biomass feedstock to prepare biochars under different pyrolysis temperatures (200–700 °C). The impact of biomass feedstock on formation of biochar-bound EPFRs was systematically compared. Elemental compositions and atomic ratios of H/C and O/C varied greatly among different biomass feedstocks and the subsequently resulting biochars. EPFRs in biochars derived from the studied lignocellulosic biomass have similar levels of spin concentrations (10¹⁸–10¹⁹ spins per g) except for lower EPFRs in biochars under 200 and 700 °C; however, sludge-based biochars, a typical non-lignocellulosic-biomass-based biochar, have much lower EPFRs (10¹⁶ spins per g) than lignocellulosic-biomass-based biochars under all the studied pyrolysis temperatures. Values of g factors ranged from 2.0025 to 2.0042 and line width was in the range of 2.15–11.3 for EPFRs in the resulting biochars. Spin concentrations of biochar-bound EPFRs increased with the increasing pyrolysis temperatures from 200 to 500 °C, and then decreased rapidly from 500 to 700 °C and oxygen-centered radicals shifted to carbon-centered radicals with the increasing pyrolysis temperatures from 200 to 700 °C for all the studied biomass feedstock. 300–500 °C was the appropriate pyrolysis temperature range for higher levels of spin concentrations of biochar-bound EPFRs. Moreover, EPFRs'' concentrations had significantly positive correlation with C contents and weak or none correlation with contents of transition metals. Overall, different types of biomass feedstock have significant impact on the formation of EPFRs in the resulting biochars.

Environmentally persistent free radicals (EPFRs) in biochars have the ability of catalytic formation of reactive oxygen species, which may pose potential oxidative stresses to eco-environment and human health.     

An efficient,mild and metal free l-proline catalyzed construction of fused pyrimidines under microwave conditions in water

One-pot condensation of 4-hydroxy coumarins, aldehydes and urea/thiourea to build C–C and C–N bonds is described. Fused pyrimidines have been synthesized under mild reaction conditions using l-proline. The protocol has been performed rapidly and efficiently in water under metal free conditions. Heterocyclic derivatives have been synthesized using the present methodology and avoid the use of hazardous solvents over conventional organic solvents. A proposed mechanism could be established for three component reactions. The present study reveals the first case in which l-proline has been explored as a homogeneous catalyst in the synthesis of fused pyrimidines in water under microwave irradiation. This synthesis involves simple workup and acceptable efficiency. The most notable feature of this protocol is the ability of the catalyst to influence asymmetric induction in the reaction.

One-pot condensation of 4-hydroxy coumarins, aldehydes and urea/thiourea to build C–C and C–N bonds is described.