氘代苯胺类化合物的合成

报道了一种合成氘代苯胺类化合物的新方法。在SOCl₂介导下,以碘代苯胺类化合物和重水为原料,经碘-氘交换反应合成了一系列氘代苯胺类化合物,收率62%～95%,氘同位素丰度>97 atom%,其结构经¹H NMR, ¹³C NMR, IR和HR-MS(EI)表征。并初步探讨了反应机理。     

氘代AZD9291的合成

吲哚和2,4-二氯嘧啶经偶联反应制得3-(2-氯嘧啶-4-基)-1H-吲哚(1); 1与CD₃I 经取代反应制得3-(2-氯嘧啶-4-基)-1-(甲基-d₃)-吲哚(2); 2经两步亲核取代反应制得N′-(2-二甲基氨基乙基)-2-甲氧基-N′-甲基-N-{［4-(1-(甲基-d₃)吲哚-3-基)］嘧啶-2-基}-5-硝基苯-1,4-二胺(4); 4经还原反应后,与氯丙酰氯发生缩合反应合成了氘代AZD9291,总收率8.5%,其结构经¹H NMR, ¹³C NMR和ESI-MS表征。     

Brazilin类似物的合成

以3-(3,4-二甲氧苯基)丙酸为原料, 经分子内傅-克反应、双羟基化、Lombardo 反应, 高价碘的氧化及类Pinacol重排等共10步反应, 完成了brazilin类似物的合成.     

氘代阿戈美拉汀的合成

以苯酚为原料,氘代碘甲烷与氘代醋酸酐为氘代试剂.经过氘代甲基化、傅克酰基化、克脑文盖尔缩合、芳构化、还原及氘代乙酰化反应得到氘代标记的阿戈美拉汀(1).该合成路线简洁,原料易得、反应条件易于控制,总收率为15.2%,化学纯度为99.97%,氘代丰度大于98%.目标化合物结构经质谱、核磁共振等表征确定可用于其药代动力学研究.     

Indoprofen类似物的合成和表征

以邻硝基苯甲醛为超始原料，合成2-溴甲基-3-喹啉酸乙酯中间体，其分别与 苯胺、2-氯代苯胺、3-氯代苯胺、2-甲基苯胺和3-甲基苯胺发生Williamson反应， Williamson反应产物经闭环反应，得到新化合物2，3-二氢-1-氧代-2-苯基-1H-吡 咯并[3，4-b]喹啉（4a），2，3-二氢-1-氧代-2-（2-氯代苯基）-1H-吡咯并[3， 4-b]喹啉（4b），2，3-二氢-1-氧代-2-（3-氯代苯基）-1H-吡咯并[3,4-b]喹啉（ 4c），2，3-二氢-1-氧代-2-（2-甲基苯基）-1H-吡咯并[3，4-b]喹啉（4d）和2， 3-二氢-1-氧代-2-（3-甲基苯基）-1H-吡咯并[3，4-b]喹啉（4e）。12个新化合物 由元素分析、红外光谱、核磁共振氢谱、质谱予以证实。     

5-氘代利巴韦林衍生物的合成

报道了5位被氘原子取代的抗病毒药物利巴韦林的合成新方法.在曙红Y(Eosin Y)催化和蓝光照射下,5-巯基-3-甲基-1,2,4-三氮唑的硫原子转化为氘原子,接着甲基被KMnO4氧化为羧基,然后在H2SO4/CH3OH体系中羧基发生甲酯化反应,得到5-氘代-1,2,4-三氮唑甲酯.最后5-氘代-1,2,4-三氮唑甲酯...     

二茂铁基1,4-Dihydropyridine类似物的合成

1 ,4 二氢吡啶衍生物是一类有着多种生物活性的化合物 ,具有扩张血管、抗高血压、抗动脉粥状硬化、抗肿瘤、抗糖尿病、抗衰老等作用 ,是七十年代以来相继开发的一类新型高效的钙离子拮抗剂 ,临床上用于治疗高血压、心绞痛、充血性心衰和动脉粥状硬化等心脑血管疾病及肠胃疾病、雷诺氏病 ,还可以作为辅佐药物治疗肺动脉高压和癫痫病[1 ] 。近年来 ,二茂铁衍生物在生物学、医学等方面得到了广泛的研究和应用 ,主要是由于它们的结构和性质有自身的特殊性 :二茂铁有卓越的芳香性 ,易发生取代反应 ,易进行修饰 ,并且在许多介质中有较好的稳定性 ;…     

Aspernigerin类似物的合成及生物活性研究

以天然产物Aspernigerin为先导,将Aspernigerin结构中的一个1,2,3,4-四氢喹啉基团以芳胺类化合物替代,设计合成了15个未见文献报道的Aspernigerin类似物,结构均经过1H NMR,IR和元素分析确证.初步生物活性测试表明,大部分目标化合物均表现出了一定的杀虫和杀菌活性,其中化合物2n在200μg/mL的浓度下对小菜蛾仍表现出100%的杀虫活性,优于先导Aspernigerin和对照药剂噻虫嗪;化合物2d,2e,2j,2k表现出对黄瓜灰霉病优于先导Aspernigerin的抑制活性.     

DNJ-C-6氘代衍生物合成及生物活性测试

以1-脱氧野尻霉素(DNJ)为原料,通过新设计路线合成中间体N-苄氧羰基-2,3,4,6-四-O-苄基-1-脱氧野尻霉素,并在此中间体的基础上通过氧化、氘代硼氢化钠还原,脱保护得到C-6氘代DNJ衍生物,最后考察了目标化合物对α-糖苷酶抑制活性。     

Synthesis of Regioselectively Deuterated Cyclopropanes

A regioselective synthesis of deuterated aliphatic cyclopropanes has been developed to furnish labeled substrates for gas-phase ion-molecule reaction studies.     

Simple Synthesis of Deuterated Pterosines

Ptaquiloside, a potent carcinogen present in bracken fern, a plant consumed by farm animals, may be detected in traces by converting it into the bromopterosine. A simple synthesis of bromopterosine d₂, to be used as standard in GC/MS or LC/MS analyses, is described.     

Synthesis of Pseudobaptigenin Analogs

Homologs of the natural isoflavonoid pseudobaptigenin containing benzodioxane and benzodioxepane fragments were synthesized. Methanesulfonyl, carbamoyl, aminomethyl, and coumarin-containing isoflavone derivatives were prepared.     

Synthesis of Phenylalanine Analogs

A straightforward synthesis of phenylalanine analogs is described. Cerium ammonium nitrate (CAN) mediated addition of azide to cinnamic ester, followed by reaction with sodium acetate afforded the α‐azidocinnamate in moderate yield. Hydrogenation of α‐azidocinnamate, followed by BOC, CBZ or Fmoc protection gave phenylalanine analogs. A new approach for synthesizing racemic p‐boronophenylalanine analog was also explored.     

Synthesis of Formononetin Analogs

Derivatives of the natural isoflavone formononetin were synthesized. Acylation and alkylation of the phenolic hydroxyls and the chromone ring were investigated.     

Reversed-Phase High Pressure Liquid Chromatography Separation of Deuterated Compounds of Biological Importance from Their Protio Analogs

Abstract

A rapid and a practical HPLC method with UV-VIS detection was developed for the separation and analysis of deuterated carotenoids from their protio analogs. Four different chromatography systems were developed. The results showed that with reversed-phase C₁₈ columns it was possible to baseline resolve fully deuterated carotenoids from the nondeuterated analogs. In all instances the deuterated compound eluted ahead of its protio analog indicating that van der Waals forces are operational during the separation process. Specificity, sensitivity, and reproducibility make these methods particularly suitable in plant chemistry for semi-preparative purification processes and methodologies.     

Synthesis of Cytotoxic Isodeoxypodophyllotoxin Analogs

A series of aryltetralin lignans 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j , 7k , 7l were synthesized as cytotoxic isodeoxypodophyllotoxin analogs. The title compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j , 7k , 7l were synthesized from the reaction of (+)‐(R )‐4‐[benzo(d )(1,3)dioxol‐5‐ylmethyl]‐dihydrofuran‐2‐(3H )‐one with different arylaldehydes to afford benzyl alcohol analogs and subsequent cyclization with trifluoroacetic acid in dichromethane. The preliminary screening of the compounds against viability of blood cancer human cell line K562 revealed that compounds 7d , 7e , and 7f had higher inhibitory activity at 10 µg/mL concentration compared with etoposide as reference drug.     

One-Pot Synthesis of Phenytoin Analogs

A series of phenytoin analogs (5,5-diphenylimidazolidine-2,4-dione or 5,5-diphenyl-hydantoin) were synthesized in 65–75% yield from the corresponding substituted benzils. The same products were also obtained directly from -hydroxy ketones via one-pot procedure.