First total synthesis of the marine steroid alkaloid plakinamine B

The first total synthesis of the marine steroid alkaloid plakinamine B (1) was accomplished in seven steps starting from known aldehyde 3. Key steps in this synthesis are the attachment of a vinylpyridine side chain by an aldol reaction, a chemoselective reduction of a pyridinium salt to a vinyl tetrahydropyridine, and the introduction of the 3α-methylamino group under Mitsunobu conditions. Plakinamine B and some of its precursors with amino or pyridinium side chains show significant antimicrobial activities.     

Substituent effects on the redox potentials of dihydroxybenzenes: theoretical and experimental study

The redox reactions of p-hydroquinone and pyrocatechol undergo a two-proton-two-electron process in aqueous solution. We calculated their redox potentials at the B3LYP/6-311+G(d,p) level, and verified the values by employing cyclic voltammetry experiments. Then we selected seven substituent groups (–F, –Cl, –OH, –COOH, –CN, –NH₂, and –NO₂ groups) to systematically investigate the substituent effect, including the sort, position, and number of the substituent, on the redox potentials of p-hydroquinone and pyrocatechol. The calculated results show that –NH₂ and –OH groups can decrease the redox potentials, while –F, –Cl, –COOH, –CN, and –NO₂ groups increase the potential values of p-hydroquinone and pyrocatechol. The calculations can accurately predict the substituent effects on the redox potentials of pyrocatechol and p-hydroquinone. We would expect that the accurate calculation results for the model systems could be applied in the prediction of electrode potentials of other molecules.     

Syntheses of nucleosides with 2′-spirolactam and 2′-spiropyrrolidine moieties as potential inhibitors of hepatitis C virus NS5B polymerase

To discover novel nucleosides as potential antiviral agents, 2′-spirolactam and 2′-spiropyrrolidine-containing nucleoside analogs were envisioned. Efficient synthetic routes were developed with an epoxide opening as the key step to establish the quaternary center at the 2′ position, leading to the design and synthesis of uridine analogs 8 and 21, prodrugs 13–16, and cytidine analog 11.     

Two novel abietane dimers from transformed root cultures of Salvia broussonetii

Broussonetone A (1) and broussonetone B (2), two novel dimeric abietane diterpenes, have been isolated from Salvia broussonetii root cultures transformed by Agrobacterium rhizogenes. The structure of broussonetone A was determined from spectroscopic data and confirmed by X-ray analysis. This dimer can be formed by a [4+2]-cycloaddition of two molecules of 13β-hydroxyabieta-8(14),9(11)-dien-12-one. NMR data of broussonetone B indicated that the C-20 methyl in part B of the broussonetone A molecule had been substituted by an aldehyde group. Thus, broussonetone B could be formed by an analogous Diels Alder reaction between 13β-hydroxyabieta-8(14),9(11)-dien-12-one as the dienophile and its 20-oxo derivative as the electrophile.     

Optimised synthesis of diamino-triazinylmethyl benzoates as inhibitors of Rad6B ubiquitin conjugating enzyme

Recently, we have identified the first inhibitors of Rad6B, an E2 enzyme essential for post-replication DNA repair and a potential new drug target for the treatment of breast cancer. We report two newly optimised synthetic routes to our [4-amino-6-(phenylamino)-1,3,5-triazin-2-yl]methyl 4-nitrobenzoate target compounds TZ8 and TZ9 with general applicability for further structure–activity relationship studies around this pharmacophore. The key step involved the condensation/cyclisation between phenylbiguanide and either ethyl bromoacetate or dimethyloxalate in good yield.     

Syntheses of 4′-spirocyclic phosphono-nucleosides as potential inhibitors of hepatitis C virus NS5B polymerase

To discover novel nucleosides as potential antiviral agents, 4′-spirocyclic phosphono-nucleosides were designed to mimic the monophosphate of R-1479, a known nucleoside inhibitor of HCV NS5B. Bypassing the first kinase step to nucleoside monophosphate is viewed as advantageous since this phosphorylation is often observed as the rate-limiting transformation to the active NTP for many nucleosides. Efficient synthetic routes were developed with a triphenylphosphine–iodine cyclization reaction as the key step to form the tetrahydrofuran 4′-spirocycle. The desired 4′-spirocyclic phosphono-cytidine analogs 12a, 12b, and 16 were prepared in 11 steps.     

利用无标记的分子信标及核酸染料SYBR Green Ⅰ检测乙肝病毒

本文以野生型的乙型肝炎病毒(HBV)核酸片段为研究对象,利用无标记的分子信标及核酸染料SYBR Green I,建立了一种高灵敏、高选择性的特定序列核酸检测方法.在优化条件下,目标DNA浓度为4×10-11~400×10-11 mol/L之间时,SYBR Green I的荧光强度(ΔI)与目标DNA的浓度(C)具有良好的线性关系,其拟合的回归方程为ΔI=1.9556 C+31.4659(R2=0.9956),方法检测限(3ζ)为2×10-11 mol/L.该方法操作简单、检测速度快、灵敏度高、重现性好、检出限低.利用该方法,结合不对称PCR技术,实现了对HBV的定量检测.     

一例水溶液中识别铜离子的染料探针

通过罗丹明B与乙二胺反应生成的中间体合成了一例可以对铜离子进行比色检测的探针R-Cu.R-Cu可以实现对在HEPES(5 mmol/L;pH 7.4)溶液中Cu2+的比色可视化识别,加入Cu2+后,R-Cu的吸收明显增强,呈现出罗丹明B的紫红色.探针对Cu2+具有较高的选择性和灵敏性,对其他常见的金属离子具有较强的抗干扰能力.该探针可以在较宽的特别是近中性pH环境下有效检测Cu2+,最低检出限为2.70×10?7 mol/L.     

Voltammetric Determination of Aflatoxin B1

For the first time the possibility of voltammetry used for the determination of aflatoxin B1 on a glassy carbon electrode was shown. The effect of pH of a supporting electrolyte on the analytical signal of aflatoxin B1 has been investigated and it was shown that there is a more pronounced peak with a maximum current at pH of 5.33. The most favorable supporting electrolyte for a linear range of detectable concentrations of aflatoxin B1 – 0.1 M (NH₄)₂SO₄ was determined. The results of research on the development of conditions of voltammetric measurement of aflatoxin B1 are presented.     

Identification of metabolites of Ginkgolide B in vivo and in vitro using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

Ginkgolide B is a dietary diterpene with multiple pharmacological activities. However, current research on ginkgolide B is not comprehensive. The current study analyzed the metabolic profile of ginkgolide B in vivo and in vitro using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To detect and identify the different metabolites in ginkgolide B, a novel data processing method was used as an assistant tool. A total of 53 different metabolites of ginkgolide B (38 phase I metabolites and 15 phase II metabolites) were detected relative to blank samples. The biotransformation route of ginkgolide B was identified as oxidation, dehydroxylation, hydrogenation, decarbonylation, demethylation, sulfate conjugation, glucose conjugation, methylation, and acetylation. The current study demonstrated a method for rapidly detecting and identifying metabolites and provided useful information to further characterize the pharmacology and mechanism of ginkgolide B. A method for the analysis of other diterpene metabolic components in vivo and in vitro was also established.