6-取代氨基-2-烷硫基腺苷化合物的合成及抗血小板凝聚活性

以鸟苷(1)为原料, 经过糖环保护得到2',3',5'-三-O-乙酰基鸟嘌呤核苷(2), 化合物2与三氯氧磷反应得到2-氨基-6-氯-9-(2',3',5'-三-O-乙酰基-β-D-呋喃核糖基)嘌呤(3), 化合物3经重氮化后再与二烷基二硫醚反应得到2-烷硫基-6-氯-9-(2',3',5'-三-O-乙酰基-β-D-呋喃核糖基)嘌呤(4a~4d), 化合物4a~4d与胺进行亲核取代反应后, 脱去糖环保护得到12个新型的6-取代氨基-2-烷硫基腺苷化合物(5a~5l). 采用¹H NMR, ¹³C NMR, IR和高分辨质谱(HRMS)对目标化合物的结构进行了确证, 并对所有化合物进行了体外抗血小板聚集活性测试. 结果表明, 当测试浓度为10 μmol/L时, 化合物5a~5l仍具有一定的抗凝活性, 其中, 6-(3-苯基丙基)氨基-2-丙硫基腺苷(5d)活性最为显著, 抑制率可达90.2%.     

无溶剂、无催化剂条件下α-腺嘌呤阿拉伯糖苷的合成

为了发展有效合成α-腺嘌呤阿拉伯糖苷的方法,以1,2,3,5-四-O-乙酰基-β-D-阿拉伯糖和6-氯嘌呤为原料,在微波辐射和无溶剂、无催化剂条件下反应得到中间体9-α-D-(2',3',5'-三-O-乙酰基)阿拉伯呋喃糖基-6-氯嘌呤,收率85%。 该中间体物在Na₂CO₃催化下脱除乙酰基,然后“一锅”加入饱和的NH₃/CH₃OH溶液氨解,以90%的收率得到α-腺嘌呤阿拉伯糖苷。 关键中间体9-α-D-(2',3',5'-三-O-乙酰基)阿拉伯呋喃糖基-6-氯嘌呤的合成反应规模可以扩大到100 g。 类似地合成α-2-氟腺嘌呤阿拉伯糖苷和α-2-氨基腺嘌呤阿拉伯糖苷。     

2-碘腺苷合成新方法

报道了核苷药物中间体2-碘腺苷的合成新方法.以2-氨基-6-氯-2′,3′,5′-三-O-乙酰基嘌呤核苷为原料,以CH3CN为溶剂,I2为碘源,5%的Cu I为催化剂,合成了到2-碘-6-氯-2′,3′,5′-三-O-乙酰基嘌呤核苷,继而在饱和的NH3/CH3OH溶液中氨解,以两步和78.2%的总收率得到2-碘腺苷.反应规模可以扩大到公斤级,收率没有降低.中间体及产物的分离、纯化不需要柱层析.该方法高效、简便、易于操作,显示出很好的应用前景.     

无溶剂、无催化剂条件下α-腺嘌呤阿拉伯糖苷的合成

为了发展有效合成α-腺嘌呤阿拉伯糖苷的方法,以1,2,3,5-四-O-乙酰基-β-D-阿拉伯糖和6-氯嘌呤为原料,在微波辐射和无溶剂、无催化剂条件下反应得到中间体9-α-D-(2',3',5'-三-O-乙酰基)阿拉伯呋喃糖基-6-氯嘌呤,收率85%。该中间体物在Na2CO3催化下脱除乙酰基,然后"一锅"加入饱和的NH3/CH3OH溶液氨解,以90%的收率得到α-腺嘌呤阿拉伯糖苷。关键中间体9-α-D-(2',3',5'-三-O-乙酰基)阿拉伯呋喃糖基-6-氯嘌呤的合成反应规模可以扩大到100 g。类似地合成α-2-氟腺嘌呤阿拉伯糖苷和α-2-氨基腺嘌呤阿拉伯糖苷。     

微波辐射下水中6-氯嘌呤(核苷)及8-溴嘌呤核苷的脱卤反应

以6-氯嘌呤,6-氯嘌呤核苷或8-溴嘌呤核苷为原料,微波辐射下与水合肼反应生成相应的6-肼嘌呤(2a～2e),6-肼嘌呤核苷(2f和2g)或8-肼嘌呤核苷(2h和2i);2在微波辐射下经Wolff-Kishner-HuangMinlon还原反应得到6-脱氯嘌呤,6-脱氯嘌呤核苷或8-脱溴嘌呤核苷,总收率46%～83%,其结构经1HNMR和13CNMR表征。     

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.     

新型2,6-二取代嘌呤衍生物的合成及其抗肿瘤活性

以2,6-二氯嘌呤为原料,对其2-位和6-位进行结构修饰,合成了8个新型2,6-二胺嘌呤类衍生物(3a~3h),其结构经¹H NMR, IR和MS（ESI）表征。采用MTT法研究了3a~3h对人胃癌SGC-7901细胞的体外抗肿瘤活性。结果表明: 3a, 3b, 3c, 3g具有良好的抗肿瘤活性,其中3c（IC₅₀ 65.01 μmol·L^-1）对人胃癌细胞SGC-7901的抑制作用最强。     

N6-烷基-2-烷氧基腺苷化合物的合成及抗血小板凝集活性

以鸟瞟呤核苷(1)为原料,经羟基保护得到2’,3’,5’-三-O-乙酰基鸟嘌呤核苷(2),2与三氯氧磷反应得到2-氨基-6-氯-9-(2’,3’,5’-三-O-乙酰基-β-D-呋喃核糖)嘌呤(3),3经重氮化、水解和O-烷基化得到2-烷氧基-6-氯-9-(2’,3’,5’-三-O-乙酰基-β-D-呋喃核糖)嘌呤(4a～...     

抗白血病药物克拉屈滨的合成

报道了抗白血病药物克拉屈滨的合成新方法:在NaH作用下,廉价易得的6-氯嘌呤高选择性地在β位和1-氯-2-脱氧-3,5-二-O-对氯苯甲酰基-D-核糖缩合;β-缩合物的2位在三氟乙酸酐和四丁基硝酸铵作用下引入硝基;在NH₄Cl/EtOH作用下,2-硝基转化为2-氯;最后在饱和NH₃/CH₃OH溶液中完成保护基脱除和6-氯氨解两步反应,以4步共43.5%的总收率得到抗白血病药物克拉屈滨。 该方法完全避免了α异构体的生成,原料廉价易得,分离纯化不需柱层析,且反应扩大到100 g规模时,收率无下降,具有较好的应用前景。     

2-氯腺苷的合成研究

以价格低廉的商品化2',3',5'-三-O-乙酰基鸟苷为原料,和POCl3反应,将6位羰基转化为Cl,继而用亚硝酸叔丁酯和Sb Cl3体系,将2-NH2转化为Cl,最后在饱和的NH3/CH3OH溶液中选择性地将6-Cl氨解为-NH2,同时脱除乙酰基,以3步和72%的总收率得到2-氯腺苷。该方法不需要重金属催化剂,原料价格低廉,产物成本低,易于扩大生产。     

A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-guanosine.

Peroxynitrite reacts with 2',3',5'-tri-O-acetyl-guanosine to yield a novel compound identified as 1-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6). This characterization was achieved using a combination of UV/vis spectroscopy and ESI-MS. Additionally, 1-(beta-D-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6a) was synthesized by an independent route, characterized by UV/vis spectroscopy, ESI-MS, and (1)H- and (13)C NMR, and shown to be identical to deacetylated 6. This product is extremely stable in aqueous solution at both pH extremes and is formed in significant yields. These characteristics suggest that this lesion may be useful as a specific biomarker of peroxynitrite-induced DNA damage. We also observed formation of 2',3',5'-tri-O-acetyl-8-nitroguanosine (2',3',5'-tri-O-acetyl-8-NO(2)()Guo), 2-amino-5-[(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one (2',3',5'-tri-O-acetyl-Iz), and the peroxynitrite-induced oxidation products of 2',3',5'-tri-O-acetyl-8-oxoGuo. The formation of 6 and 2',3',5'-tri-O-acetyl-8-NO(2)()Guo was rationalized by a mechanism invoking formation of the guanine radical.     

Generation of thiyl radicals by the photolysis of 5-iodo-4-thiouridine

The photochemistry of 2',3',5'-tri-O-acetyl-5-iodo-4-thiouridine (3) in deoxygenated 1:1 CH(3)CN-H(2)O pH 5.8 (phosphate buffer) solution has been studied by means of steady-state and nanosecond laser flash photolysis methods. Under steady-state irradiation (lambda > or = 334 nm), the stable photoproducts were iodide ion, 2',3',5'-tri-O-acetyl-4-thiouridine (4), and two disulfides. The disulfides were the symmetrical bis-(2',3',5'-tri-O-acetyl-5-iodo-4-thiouridine) (5) and unsymmetrical 6, which contains both 4-thiouridine and 5-iodo-4-thiouridine residues. The formation of the dehalogenated photoproduct suggests that C(5)-I bond cleavage is a primary photochemical step. Attempts to scavenge the resulting C(5)-centered radical by suitable addends, bis-(N-alpha-acetyl)cystine-bis-N-ethylamide or benzene, were unsuccessful. Analysis of the photoproducts formed under these conditions showed that the S-atom is the reactive center. The photoproduct 4, obtained by irradiation of 3 in CD(3)CN-H(2)O, followed by reversed-phase HPLC isolation using nonlabeled eluents, did not contain deuterium. An analogous experiment performed in CH(3)CN-D(2)O gave deuterated product 4-d with 88% of the deuterium incorporated at C(5). Transient absorption observed upon laser excitation (lambda= 308 nm) of 3 was assigned to the 4-uridinylthiyl radical on the basis of the similarity of this spectrum with that obtained upon laser photolysis of the disulfide: bis-(2',3',5'-tri-O-acetyl-4-thiouridine) 14. On the basis of the results of steady-state and laser photolysis studies, a mechanism of the photochemical reaction of 3 is proposed. The key mechanistic step is a transformation of the C(5)-centered radical formed initially by C(5)-I bond cleavage into a long-lived S-centered radical via a 1,3-hydrogen shift. Theoretical calculations confirmed that the long-lived S-centered radical is the most stable radical derived from the 4-thiouracil residue.     

Synthesis of novel interlocked systems utilizing a palladium complex with 2,6-pyridinedicarboxamide-based tridentate macrocyclic ligand

A new protocol for the high yield synthesis of interlocked molecules is described. Palladium(II) complex including a 2,6-pyridinedicarboxamide-based tridentate macrocycle 2 was allowed to react with a 2,6-disubstituted pyridine derivative bearing two hydroxyl groups at both termini 3b to yield the corresponding Pd(II) complex 4b quantitatively. An acid catalyzed end-capping of 4b with a bulky isocyanate gave Pd(II) complex 5b in 96% yield, which was treated with carbon monoxide to afford [2]rotaxane 6b quantitatively.     

The pH-dependent role of superoxide in riboflavin-catalyzed photooxidation of 8-oxo-7,8-dihydroguanosine

[reaction: see text]. The riboflavin-catalyzed photooxidation of 2',3',5'-tri-O-acetyl-8-oxo-7,8-dihydroguanosine generates a radical intermediate that is competitively trapped by H(2)O, O2(-)(*), or O(2). The products of H(2)O trapping have been previously described as the spiroiminodihydantoin (pH >or= 7) and iminoallantoin/guanidinohydantoin (pH < 7) nucleosides. Trapping by O2(-)(*) leads to the oxaluric acid (pH or= 8.6) pathways (R' ', R' ' = H or 2,3,5-tri-O-Ac-ribofuranosyl). The pH-dependent role of superoxide was probed using Mn-SOD and compared to guanosine and 8-methoxyguanosine photooxidation.     

Regioselective Cycloaddition of the Dimethyl Ester of Acetylenedicarboxylic Acid to 2,4,6-Triazidopyridines

2,4,6-Triazido-3,5-dichloropyridine was obtained in the reaction of pentachloropyridine with sodium azide. At room temperature, this azide reacts regioslectively with norbornene at the -azide group to give the corresponding 4-(3-azatricyclo[3.2.1.0]octanyl)-2,6-diazidopyridine in 88% yield. The cycloaddition of the dimethyl ester of acetylenedicarboxylic acid to this triazide proceeds at the azide groups at C₍₂₎ and C₍₆₎ in the pyridine ring to give 4-azido-2,6-di(4',5'-dimethoxycarbonyl)-1H-1,2,3-triazolopyridine. The analogous reaction of 2,4,6-triazido-3,5-dicyanopyridine with the dimethyl ester of acetylenedicarboxylic acid stops at the formation of 2,4-diazido-6-(4',5'-dimethoxycarbonyl)-1H-1,2,3-triazolopyridine. In contrast to reactions with electron-rich dipolarophiles, the cycloaddition of electron-deficient dipolarophiles to 2,4,6-triazidopyridines proceeds with thermodynamic control primarily a! t the azide groups bearing the highest orbital density in the HOMO.     

Dithienothiophene (DTT)-based dyes for dye-sensitized solar cells: synthesis of 2,6-dibromo-DTT

A one-pot synthesis of 2,6-dibromodithieno[3,2-b;2',3'-d]thiophene (dibromo-DTT, 4) was developed. A key step was bromodecarboxylation of DTT-2,6-dicarboxylic acid, obtained by saponification of the diester 1. The donor-acceptor dye DAHTDTT (13), based on a central 2,6-bis[2'-(3'-hexylthienyl)]dithieno[3,2-b;2',3'-d]thiophene core (9), was prepared and incorporated in a dye-sensitized solar cell (DSC), which exhibited an energy conversion efficiency of 7.3% with V(oc) of 697 mV, J(sc) of 14.4 mA/cm(2), and ff of 0.73 at 1 sun.     

2，6-二氨基-3，5-二硝基-1-氧吡嗪合成中的氧化方法改进

以磁性Fe3O4负载质子化过氧钨酸盐为催化剂,在不用三氟乙酸的情况下,以双氧水为氧化剂,将2,6-二甲氧基吡嗪、2,6-二氯吡嗪和2-氯-6-甲氧基吡嗪高效地氧化为其相应的氮氧化物2,6-二氨基-3,5-二硝基-1-氧吡嗪(LLM-105)。 典型条件为：底物10 mmol,CH3CN 30 mL,催化剂Fe3O4/CS/HWO 0.1 g(约0.1 mmol),60 ℃分5次逐滴加入30%双氧水5 mL。 反应混合物溶液经萃取和柱色谱法提纯,得产物,收率一般为60%~73%。 使用高斯03量化计算程序对氧化过程进行了理论计算,结果与实验数据相符。     

Triphosphane formation from the terminal zirconium phosphinidene complex [Cp2Zr=PDmp(PMe3)] (Dmp=2,6-Mes2C6H3) and crystal structure of DmpP(PPh2)2

The new terminal phosphinidene complex [Cp₂Zr=PDmp(PMe₃)] (Dmp=2,6-Mes₂C₆H₃; 1) was prepared in 81% yield by the reaction of [Li(Et₂O)][P(H)Dmp] with [Cp₂Zr(Me)Cl] in the presence of excess PMe₃. Compound 1 reacts with Ph₂PCl to produce selectively the sterically congested triphosphane DmpP(PPh₂)₂ (2) and [Cp₂ZrCl₂] in high yields. The structure of 2 obtained by X-ray diffraction analysis of a single crystal reveals phosphorus–phosphorus bond lengths of 2.251(2) and 2.234(2) Å and a PPP bond angle of 105.46(6)°.     

由2',4'-二氢-6'-甲氧基-3',5'-二甲基查耳酮合成新黄酮

在DMSO/ I2的氧化作用下,由2',4'-二氢-6'-甲氧基-3',5'-二甲基查耳酮可合成一种全新结构的黄酮:7-羟基-5-甲氧基-6,8-二甲基黄酮(产率91%),而在HCl/MeOH作用下则得到了两种黄烷酮:7-羟基-5-甲氧基-6,8-二甲基黄烷酮 (产率70%) 和 5,7-二羟基-6,8-二甲基黄烷酮 (产率20%).