通过不对称氢转移/动态动力学拆分合成碳环N^3-嘌呤核苷

N^3-嘌呤核苷由于可能同时被嘌呤和嘧啶代谢酶识别,因而有望作为双靶点药物应用于抗病毒治疗.报道了一种以α-(N^3-嘌呤)取代的环烷酮为原料,通过不对称氢转移反应实现动态动力学拆分,高收率高立体选择性地合成系列碳环N^3-嘌呤核苷化合物.该催化体系也适用于α-嘧啶取代的环烷酮底物,且产物通过进一步衍生,合成了2’-F-,Ac S-,N^3-修饰的碳环嘧啶核苷.     

通过不对称氢转移/动态动力学拆分合成碳环N~3-嘌呤核苷（英文）

N~3-嘌呤核苷由于可能同时被嘌呤和嘧啶代谢酶识别,因而有望作为双靶点药物应用于抗病毒治疗.报道了一种以α-(N~3-嘌呤)取代的环烷酮为原料,通过不对称氢转移反应实现动态动力学拆分,高收率高立体选择性地合成系列碳环N~3-嘌呤核苷化合物.该催化体系也适用于α-嘧啶取代的环烷酮底物,且产物通过进一步衍生,合成了2'-F-,Ac S-,N~3-修饰的碳环嘧啶核苷.     

钯/乙酸亚铜共同促进的嘧啶硫醚的脱硫碳碳偶联反应

报道了一种钯催化、乙酸亚铜盐促进的嘧啶硫醚/喹啉硫醚与炔烃或芳基硼酸的脱硫碳碳偶联反应,合成了一系列2-炔基嘧啶和2-芳基嘧啶/喹啉衍生物,产率良好(64%～87%).所用的乙酸亚铜盐廉价、稳定,反应产率高,底物适用范围较广.     

咪唑啉盐向邻苯二胺转移一碳单元反应的理论研究

酶催化的一碳单元转移反应在生物合成和代谢过程中具有重要的作用 ,并与抗癌药物设计和合成密切相关 .虽然催化不同一碳单元转移反应的酶不同 ,但大多数酶需要四氢叶酸作辅酶 .四氢叶酸辅酶传递一碳单元的化学与其Ｎ5,Ｎ1 0的ΔｐＫａ 密切相关 ,而与嘧啶环及谷氨酸残基部分无关 ,后两部分的作用是把辅酶结合在适当的酶蛋白表面上[1 ] .当可转移的碳处于甲酸态时 ,四氢叶酸辅酶以衍生物 5,1 0 ＣＨ+ ＴＨＦ(1 )的形式存在 ,其中可转移的碳与Ｎ5,Ｎ1 0相连形成五元环 ,是反应的活性中心 .由于酶反应体系的复杂性 ,在实验和理论研究中大多建…     

α-糜蛋白酶催化合成β-脲基巴豆酸酯

β-脲基巴豆酸酯是合成6-甲基嘧啶二酮衍生物及3,4-二氢嘧啶二酮衍生物的重要中间体,在生物制药中有着广泛的应用.由于酶具有绿色、安全、高效的催化特性,采用α-糜蛋白酶为生物催化剂,以N,N-二甲基甲酰胺为反应介质,37℃条件下,通过1,3-二羰基化合物和脲的缩合反应,合成了一系列β-脲基巴豆酸酯类化合物.     

5-取代嘧啶核苷类似物的设计、合成及生物活性研究进展

综述了近年来有关新型5-取代嘧啶核苷类似物作为潜在生物活性先导化合物的设计、合成及生物活性研究进展.该类先导物的设计与合成主要通过以下两个方面来完成:一是在嘧啶碱基的5位上引入不同的取代基;二是在嘧啶碱基5位上引入取代基的同时对核苷中的糖基进行修饰,以得到新的衍生物.本文从以上两个方面出发,介绍了近年来这一研究领域所取得的主要进展.     

新型嘧啶并二氮?衍生物的合成研究

以乙腈为溶剂,在三氯氧磷作用下,氨基嘧啶和有机酸经Bischler-Napieralski反应合成嘧啶并二氮?类砌块（2a~2e）; 2a~2e经胺基取代反应合成了一系列新型嘧啶并二氮?衍生物（3a~3e）,其结构经¹H NMR和MS(ESI)表征。     

SmI2催化合成3,4-二氢嘧啶-2-酮衍生物

3,4-二氢嘧啶-2-酮衍生物是一类具有生物活性的杂环化合物,在作为钙拮抗剂、降压剂、α1-1-a拮抗物等方面已有广泛的应用.该类化合物的合成法近十年来一直是生物活性杂环化合物领域研究的热点之一.Lewis酸催化的Biginelli反应是"一锅化"得到3,4-二氢嘧啶-2-酮衍生物的有效方法[1-5].我们以价廉易得的SmI2成功催化Biginelli反应,生成多个3,4-二氢嘧啶-2-酮衍生物.该反应无需反应溶剂,产率中等到高,且适用底物范围较广.     

NiCl2·6H2O催化的Biginelli反应－－一锅法合成3，4－二氢嘧啶－2－酮

六水合氯化镍催化下，β－酮酸酯、芳香醛和脲在无水乙醇中进行环化缩合反 应，合成了3，4－二氢嘧啶－2－酮衍生物，改进了Biginelli反应，缩短了反应时 间，且操作简便、产率高。     

复分解反应在核苷类似物合成中的应用

核苷类似物可以参与并干扰细菌（病毒）的DNA或RNA过程,抑制其生长和繁殖,从而有希望发展为抗肿瘤抗病毒药物。一些天然的核苷化合物虽然表现出一定的生理活性,在体内缺乏酶稳定性和靶向选择性却限制了其在医药领域的应用,合成具有生物活性的化学修饰的核苷及其衍生物是核酸药物化学中的重要课题。一类在金属卡宾复合物催化下的分子内或分子间烯烃重组反应-----复分解反应的发展使核苷类似物的合成进入了新阶段, 烯烃复分解反应成为核苷类似物合成的主要途径之一。随着施洛克催化剂、格拉布催化剂等复分解反应催化剂的发现和不断改进,烯烃复分解反应,尤其是关环复分解和交叉复分解反应被广泛应用于构建核苷类似物的糖环(或伪糖)结构或连接核苷类似物单体而形成核苷多聚物。本文对烯烃复分解反应在核苷类似物包括碳环核苷,2’,3’-双脱氧核苷,无环核苷,多环核苷及核苷二聚体或三聚体的合成中的应用进行了综述。     

Synthesis of 4-nitromethylene-1,4-dihydropyrimidine derivatives as pyrimidine nucleoside analogues

The synthesis of 4-nitromethylene-1,4-dihydropyrimidine derivatives as pyrimidine nucleoside analogues was developed, starting from 3-nitropyran-2-one N-functionalized amidines. Primary amines were reacted with amidines yielding 4-nitromethylene-1,4-dihydropyrimidine derivatives. In an initial survey, several 4-nitromethylene-1,4-dihydropyrimidines turned into 4-nitromethylene-1,2,3,4-tetrahydropyrimidine derivatives under different reduction conditions. The reduction reaction also induced a change in the exocyclic double bond configuration from (E) to (Z), due to an intramolecular hydrogen bond.     

Multiple tritium labelling of thymine and its derivatives

The paper deals with the synthesis of thymine and its derivatives carrying the label at C(6) in the pyrimidine in the methyl group and in deoxy-d-ribose. The molar activity of the preparations ranges from 0.85 to 4.94 PBq/mol. A procedure is proposed for obtaining tritium-labelled thymine compounds: nucleoside, nucleoside mono-, di- and triphosphates.     

L-ProT catalyzed highly regioselective N-alkoxyalkylation of purine rings with vinyl ethers

An efficient and regioselective synthesis of N-9 alkoxyalkylated purine nucleoside derivatives was achieved via the N-alkoxyalkylation of purine rings with vinyl ethers catalyzed by L-ProT.The advantages of this protocol include good to excellent yield,mild reaction condition,and simple manipulation.A plausible mechanism for the transformation was given.     

Synthesis of pyrimidine derivatives via multicomponent reaction catalyzed by ferric chloride

An eco-friendly and practical approach was developed for the synthesis of pyrimidine derivatives via a one-pot, three-component coupling reaction of commercially available aldehydes, alkynes, and indazole3/triazole catalyzed by ferric chloride with good to excellent yields. The advantages of this method include environmentally friendly catalyst, easily available materials, and ease of product isolation.     

One-pot and two-pot methods for chalcone derived pyrimidines synthesis and applications

Chalcone-derived pyrimidine is a well-known heterocyclic compound that is commonly present in ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) bio-isosteres. Pyrimidine derivatives are effective in both the electronic industry and drug industries. This review highlights the synthesis of pyrimidines, namely mono-pyrimidine, bis-pyrimidine, fused pyrimidine, symmetric, and asymmetric pyrimidine via one-pot and two-pot methods. The one-pot method is the direct reaction of amino derivatives with aldehydes and acetophenones, whereas the two-pot method is frequently reported for the synthesis of chalcone before the cyclization to a pyrimidine. This review is important in organic synthesis, particularly in the heterocyclic field, regarding pyrimidines and their significance in therapeutic and electronic industries.     

Rhodium-catalysed synthesis of fused pyrimidine derivatives employing N-sulfonyl-1,2,3-triazoles as a 1-aza-[4C] synthon

A new synthetic application of N-sulfonyl-1,2,3-triazoles acting as a 1-aza-[4C] synthon via the 1,2-shift reaction of an α-imine rhodium carbene was developed for the synthesis of fused pyrimidine derivatives. The high reactivity of the strained three-membered 2H-azirine ring facilitated the unusual cyclization of electron-deficient dienes with electron-deficient dienophiles. The compatibility was good with common functionalities tolerated. Excellent chemoselectivity was observed, and no reactions occurred between the rhodium carbene and 2H-azirine. The products could be converted into seven-membered multi-functionalized 1H-1,4-diazepine derivatives, illustrating the potential application of the protocol in medium-sized N-heterocycle synthesis.     

PdO-Catalyzed Synthesis of Tricyclic Compounds Using Biginelli-Like Reaction

An efficient method has been successfully developed for the synthesis of oxygen-bridged pyrimidine tricyclic derivatives from salicylaldehyde, ethyl acetoacete, and urea catalyzed by PdO in very good yield. A series of different oxygen-bridged pyrimidine tricyclic derivatives has been synthesized, in which two compounds’ x-ray crystal structure were obtained.     

A Novel One‐Pot Method for the Synthesis of Pyrimidine Derivatives Using Ketene N,S‐Acetal with Aryl Aldehydes

A very simple and facile one‐pot method for the synthesis of pyrimidine derivatives is presented. In this method, 2‐aryl‐pyrimidine derivatives were prepared by the reaction of ketene N,S‐acetal 1 with commercially available aryl aldehydes by heating under solvent and catalyst‐free conditions. The synthesized pyrimidine derivatives showed blue‐green fluorescence in solid state.     

Rapid formation of chemical complexity via a modified Biginelli reaction leading to dihydrofuran-2(3H)-one spiro-derivatives of triazolo[1,5-a]pyrimidine

The regio- and stereoselective, catalyst-free multicomponent synthesis of spiro-conjugated dihydrofuran-2(3H)-one/triazolo[1,5-a]pyrimidine derivatives in good to high yields via a Biginelli approach starting from ortho-substituted benzaldehydes, 3-amino-1,2,4-triazole and α-acetylbutyrolactone is reported. A plausible reaction mechanism for this transformation is discussed. The obtained heterocycles possess a drug-like conformationally restricted structure with defined stereochemistry and increased stability compared to other products obtained by this mode of the Biginelli reaction.     

Synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation catalyzed by 2-methyl-5-phenylbenzoxazolium perchlorate

Several acidic azolium salts prepared from oxazole, thiazole, and imidazole derivatives were investigated as catalysts in N-glycosylation reaction using a silylated modified pyrimidine and an acylated ribose or glucose to afford the corresponding pyrimidine nucleoside. Among the salts, 2-methyl-5-phenylbenzoxazolium perchlorate showed the highest catalytic activity. This salt is a nonhygroscopic crystalline compound that shows higher activity than the frequently used trimethylsilyl triflate. Reactions with this salt can be conducted in gram scales.