微波促进的6-位磷功能化的非环嘌呤核苷类似物的合成

以2,6-二氯嘌呤核苷和亚磷酸酯为原料,通过微波促进的Arbuzov反应,一步合成6位磷酸酯取代的嘌呤核苷类化合物,然后再进一步衍生,得到6-位磷酸单酯和6-位磷酸取代的嘌呤核苷类新化合物.得到的非环嘌呤核苷类化合物通过核磁共振图谱、高分辨质谱和红外光谱进行了结构确认.     

苄基保护的L-核苷的制备

作为主要的抗病毒药物,核苷类化合物得到了广泛应用.近年来的研究发现,一些L-型异构体比其相应的D-型异构体具有更高的抗病毒活性和更低的毒性[1],新型L-构型核苷类化合物的设计、合成的相关研究受到普遍关注.     

L-核苷类抗HIV、HBV活性化合物研究进展

抗病毒新试剂的不断涌现,为HIV、HBV感染者的临床治疗提供了有效的方法.在抗病毒试剂中,核苷类化合物占据了十分重要的地位.本文阐述了核苷类化合物抗病毒的作用机理,介绍了L型核苷的发展历史及一些新型具有抗HIV、HBV生物活性的L型核苷类化合物的分类.同时,通过对一些新型具有抗HIV、HBV生物活性的核苷类化合物如BCH、FTC、OddC、d4A、Fd4C等,D型和L型不同对映异构体抗病毒活性及生物毒性的对比发现,L型异构体比其相应的D型异构体具有抗病毒活性更高、生物毒性更低的特点.药物化学家们对此产生了极大的兴趣,进一步开展了新型L型核苷类化合物设计、合成的相关研究,以便筛选出更安全有效的抗病毒试剂.     

哒嗪核苷类的研究进展

众所周知,许多嘧啶的核苷类化合物都有较强的生理活性,其中5-氟脲苷是有效的抗癌药。而哒嗪和嘧啶在结构上具有同分异构关系,因此,对于哒嗪核苷类化合物的合成及其生     

1-(2-羟甲基-1,3-氧硫杂环戊基)吡啶酮类化合物的合成

研究了1,3-氧硫杂环戊烷核苷类似物的合成. 以吡啶酮为碱基, 利用三甲基硅基三氟甲磺酸酯(TMSOTf)催化, 与1,3-氧硫杂环戊烷发生Vorbruggen缩合反应, 合成了一系列的保护的核苷类似物, 经过进一步脱保护或者还原得到目标产物. 并测试了合成化合物的抗菌活性, 发现该类化合物对革兰氏阳性菌具有中等抑制活性.     

基于核苷类化合物HILIC-ESI-TOF/MS分析的海洋动物药指纹图谱方法

探讨了核苷类化合物指纹图谱用于不同海洋动物药真伪鉴别的可行性, 为贵重动物药的鉴别提供了一种新方法. 采用亲水色谱-电喷雾飞行时间质谱(HILIC-ESI-TOF/MS)对不同海洋动物药中的16种核苷类化合物进行分析, 构建了基于16种核苷类化合物的特征指纹图谱, 结合相似度分析和聚类分析, 用于不同海洋动物药的鉴别. 结果表明, 基于核苷类化合物HILIC-ESI-TOF/MS分析的指纹图谱能反映不同海洋动物药各自的固有特征, 结合相似度分析和聚类分析可实现对不同海洋动物药的正确区分. 说明核苷类化合物指纹图谱有望成为动物药鉴别的新方法.     

2-取代苯并噁唑类化合物合成研究进展

2-取代苯并噁唑类化合物在医药、农药以及配位催化等领域有广阔的应用前景,因而其合成方法备受关注.近年来,微波促进、水为介质、无溶剂合成、组合化学以及过渡金属催化等一系列高效、绿色的合成方法在2-取代苯并噁唑类化合物的合成中得到广泛的应用.按照不同的合成原料和合成方法进行分类,综述了近年来2-取代苯并噁唑类化合物合成研究的新进展.     

胞嘧啶核苷键联卟啉的合成及其与牛血清白蛋白的相互作用

基于卟啉化合物的光敏性和对肿瘤细胞有特殊的亲和力以及核苷类化合物的抗肿瘤及抗癌活性, 设计合成了胞嘧啶核苷卟啉化合物6和8, 其结构由¹H NMR, IR, UV-Vis, MS 和元素分析表征. 同时, 利用荧光光谱考察了上述核苷卟啉与牛血清白蛋白(BSA)的相互作用, 结果表明它们对BSA荧光有较强的静态猝灭作用.     

基于氨基酸的苯并咪唑合成研究进展

苯并咪唑类化合物在药物化学、生物化学、配位化学以及催化、分子识别、阻燃等领域具有重要应用.氨基酸类化合物是一类来源广泛的功能性合成子,因此近年来基于氨基酸的苯并咪唑合成与功能改性研究受到人们的广泛关注.综述了以各种天然与非天然氨基酸为原料,以溶液法、微波法、固相法等合成技术合成与改性苯并咪唑的新进展.     

5′-0-三苯甲基核苷衍生物的微波合成

以DMF为溶剂,二甲氨基吡啶为碱,微波辐射下核苷衍生物与三苯甲基氯反应合成了8种选择性羟基保护的5′-O-三苯甲基核苷衍生物,收率67%～87%,其结构经1H NMR和元素分析表征.     

An expeditious route toward pyrazine-containing nucleoside analogues

An improved and convenient methodology for the synthesis of asymmetrically substituted pyrazines starting from 3,5-dichloropyrazin-2(1H)-ones has been elaborated. Several nucleoside analogues have been synthesized containing the pyrazine core as the organic base coupled with the sugar via a triazole linkage. The beneficial effect of microwave irradiation throughout the sequence has been demonstrated.     

Asymmetric Synthesis of Polyhydroxy Pyrrolidinonyl Nucleoside Analogues from Tartaric acid

Modificationofnucleosideisanefficientproceduretodevelopnewpotentagentsagainsthumantum0r0rvirusesl.Morechallengingistosynthesizenew0pticallyactivepolyhydroxynucleosideanalogues.Becauseofthelimitationofresources,itseemsaratherardu0usworkt0synthesizeopticallyactivecarbocyclicorotherheterocyclicnucleosideanalogueswithmorethantwochiralcarb0ns,thoughnaturalsugarsareavaiIablestartingmaterialstooxa-cyclicnucleosides,suchasfuran0sylorpyranosylones.Inthispaper,wereportanefficientandgeneralsyntheticroute…     

An efficient solid phase synthesis of 5'-phosphodiester and phosphoramidate monoester nucleoside analogues

An easy and efficient strategy to obtain libraries of 5'-phosphodiester and 5'-phosphoramidate monoester nucleoside analogues in a highly pure form has been developed, starting from a new nucleoside based solid support. The nucleoside scaffold has been anchored through a 5'-phosphodiester linkage to Tentagel HL resin, functionalized with a 3-chloro-4-hydroxyphenylacetic linker. The solid phase synthesis of small libraries of 5'-phosphodiester and 5'-phosphoramidate monoester thymidine analogues is also reported.     

Synthesis of biologically active acycloAZT derivatives and related compounds

The synthesis of optically active acyclic analogues of 3'-azido-3'-deoxythymidine, which lack only the 2'-CH2 of the sugar, is described. The synthesis of some nucleoside analogues that contain the N-acetyl-D-neuraminic acid moiety is also described.     

Synthesis of nucleoside analogues bearing the five naturally occurring nucleic acid bases built on a 2-oxabicylo[3.1.0]hexane scaffold

Hitherto unknown nucleoside analogues incorporating the five naturally occurring nucleic acid bases built on a 2-oxabicyclo[3.1.0]hexane template were synthesized. The synthesis of these new conformationally restricted nucleoside analogues involved the preparation of a suitable sugar precursor bearing the 2-oxabicyclo[3.1.0]hexane scaffold. This sugar was readily obtained from [(3aS,6aS)-2,2-dimethyl-3a,6a-dihydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether (4) following a Simons-Smith-type cyclopropanation reaction. Finally, glycosylation reactions and deprotection provided the nucleoside analogues. Using nucleoside 14 bearing thymine base as a model, we found that the conformation of such nucleoside analogue was restricted toward a (0)T(1) conformation.     

Synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses

The synthesis of difluorinated carbocyclic analogues of 5-deoxypentofuranoses is described. The sequence involves an addition of PhSeCF₂TMS to carbohydrate-derived aldehydes followed by a radical cyclization, and provides a secure strategy for a future synthesis of pentofuranoses and nucleoside analogues.     

Click fleximers: a modular approach to purine base-expanded ribonucleoside analogues

The synthesis of nucleoside analogues incorporating 4-(5-pyrimidinyl)-1,2,3-triazole aglycons as expanded purine nucleobase mimics were accessed using the copper-catalyzed azide-alkyne Huisgen cycloaddition between a ribosyl azide and 5-alkynylpyrimidines. Depending on the nature of the alkyne employed, other nucleoside analogues that possess fluorescence or potential metal-binding properties were prepared. Computational studies were undertaken on the purine analogues and indicate that the heterocycles of the unfused nucleobase prefer a coplanar arrangement and the anti-glycosidic conformer is favoured in most instances.     

Regioselective synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues via TBS-directed 1,3-dipolar cycloaddition reaction

Herein described was a straightforward method for the highly regioselective synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues, which featured the utilization of tert-butyldimethylsilyl (TBDMS) group as the directing group in the 1,3-dipolar cycloaddition reactions. 4-tert-Butyldimethylsilyl-5-trifluoromethyl-1,2,3-triazole nucleoside analogues were generated as the only cycloaddition products in moderate yields (15-79%) via the treatment of glycosyl azides with 3,3,3-trifluoro-1-tert-butyldimethylsilylpropyne 1 in toluene at 85 °C. Removal of TBS groups in these triazole cycloadducts with tetrabutylammonium fluoride (TBAF) smoothly afforded the various 5-trifluoromethyl-1,5-disubstituted 1,2,3-triazole nucleoside analogues in good yields (40-88%).     

Synthesis of (Carbo)nucleoside Analogues by [3+2] Annulation of Aminocyclopropanes

(Carbo)nucleoside derivatives constitute an important class of pharmaceuticals, yet there are only few convergent methods to access new analogues. Here, we report the first synthesis of thymine‐, uracil‐, and 5‐fluorouracil‐substituted diester donor–acceptor cyclopropanes and their use in the indium‐ and tin‐catalyzed [3+2] annulations with aldehydes, ketones, and enol ethers. The obtained diester products could be easily decarboxylated and reduced to the corresponding alcohols. The method gives access to a broad range of new (carbo)nucleoside analogues in only four or five steps and will be highly useful for the synthesis of libraries of bioactive compounds.     

Pd-catalyzed C-C bond-forming reactions of thymidine mesitylene sulfonate

Facile synthesis of C-4 aryl pyrimidinone nucleoside analogues from an easily prepared O4-arylsulfonate derivative of thymidine is reported. Two O4-arylsulfonylthymidine precursors, (4-methylphenyl)sulfonyl and (2,4,6-trimethylphenyl)sulfonyl, were prepared and analyzed for their stabilities. Of the two, the latter possessed suitable stability as well as reactivity for Pd-catalyzed C-C bond-forming reactions with a variety of arylboronic acids. These reactions at the C-4 position are nontrivial in comparison with similar reactions at the C-5 position of pyrimidine nucleosides, with hydrolysis of the arylsulfonate precursor being a competing reaction in some cases. There are pronounced solvent influences in these reactions, but successful reactions can be attained by careful control of conditions. Many reactions proceeded efficiently at room temperature, and electron-deficient arylboronic acids can also be cross-coupled under suitable conditions. Desilylation of these products was also nontrivial, and various conditions were tested. Finally, antiviral screening was performed with the C-4 aryl pyrimidinone nucleoside analogues, but none possessed any interesting activity. The study represents the first successful synthesis of C-4 aryl pyrimidinone nucleoside analogues by cross-coupling of arylboronic acids with an arylsulfonate derived from a pyrimidine nucleoside, as well as antiviral testing of this new class of compounds.