Total synthesis and biological evaluation of (-)apicularen A and analogues thereof

Apicularen A (1) and related benzolactone acylenamines belong to a growing class of novel natural products possessing highly cytotoxic properties. The challenging structure of 1 includes a 10-membered macrolactone ring, a tetrahydropyran system, an o,m-substituted phenol and a doubly unsaturated acyl group attached on the side chain enamine functionality. The total synthesis of apicularen A described herein involves a strategy equivalent to its proposed biosynthesis and entails a reiterative two-step procedure featuring allylation and ozonolytic cleavage to grow the molecule's chain by one acetate unit at a time. The developed synthetic technology was applied to the construction of a series of apicularen A analogues whose biological evaluation established a set of structure-activity relationships in this new area of potential importance in cancer chemotherapy.     

β-内酰胺类抗生素酶促合成新进展

β-内酰胺类抗生素的合成在制药工业中占据重要的地位, 相关的酶促合成方法研究备受关注; 酶促合成显著提高合成效率, 减少三废的排放, 是实现绿色合成的有效方法. 综述了近年来β-内酰胺类抗生素酶促合成研究的新进展, 包括一锅合成法、原位产物排出法、介质技术和酶固定化方法.     

β-Lactam antibiotics. Spectroscopy and molecular orbital (MO) calculations: Part I: IR studies of complexation in penicillin-transition metal ion systems and semi-empirical PM3 calculations on simple model compounds

IR studies were preformed to determine possible transition metal ion binding sites of penicillin. the observed changes in spectral position and shape of characteristic IR bands of cloxacillin in the presence of transition metal ions (both in solutions and in the solid state) indicate formation of M–L complexes with engagement of –COO⁻ and/or –CONH– functional groups. The small shift of ν_C=O towards higher frequencies rules out direct M–L interaction via β-lactam carbonyl. PM3 calculations on simple model compounds (substituted formamide, cyclic ketones, lactams and substituted monocyclic β-lactams) have been performed. All structures were fully optimized and the calculated bond lengths, angles, heats of formation and C=O stretching frequencies were discussed to determine the β-lactam binding sites and to explain its susceptibility towards nucleophilic attack (hydrolysis in vitro) and biological activity. The relative changes of calculated values were critically compared with available experimental data and same correlation between structural parameters and in vivo activity was shown.     

分散固相萃取净化-超高效液相色谱-串联质谱法同时测定鱼和虾中抗生素及三苯甲烷类兽药残留

建立了分散固相萃取净化-超高效液相色谱-串联质谱法快速测定鱼和虾中3类（磺胺类、喹诺酮类、氯霉素类）18种抗生素及2种三苯甲烷类（孔雀石绿、隐色孔雀石绿）兽药残留。样品经磷酸氢二钾溶液水解分散，乙腈提取，提取液经氯化钠脱水、盐析后取乙腈层，经旋转蒸发仪浓缩至近干，残留物用甲醇定容至1.0 mL，C18和PSA（N-丙基乙二胺）填料分散固相萃取净化，过滤膜后经ZORBAX C18色谱柱（50 mm×2.1 mm，1.8 μm）分离，正、负离子多反应监测模式采集数据，同位素内标法定量。实验结果表明，20种兽药在0.2~300 μg/L范围内具有良好的线性关系，检出限为0.1~0.6 μg/kg，定量限为0.3~1.8 μg/kg，相关系数均大于0.99。在1、5和20倍定量限加标浓度水平下，平均回收率为72.5%~118%，相对标准偏差（RSD）为1.9%~9.8%。该方法具有前处理简单、检测效率高、成本低等优点，适用于鱼和虾中多类兽药残留的同时测定。     

A bifunctional platinum(II) complex capable of intercalation and hydrogen-bonding interactions with DNA: binding studies and cytotoxicity

The interactions of [Pt(CNN)(4-dpt)]PF(6), (1; 4-dpt=2,4-diamino-6-(4-pyridyl)-1,3,5-triazine, HCNN=6-phenyl-2,2'-bipyridine) with double-stranded DNA, poly(dA-dT)(2), and poly(dG-dC)(2) were examined by spectroscopic, electrophoretic, and hydrodynamic methods. The spectroscopic data were analyzed with McGhee, van't Hoff, and Gibbs-Helmholtz equations. In a comparative study, [Pt(CNN)(py)]PF(6) (2; py=pyridine) was prepared and the nature of its binding towards DNA was investigated [preliminary results: ChemBioChem 2003, 4, 62-68]. For reactions with calf thymus DNA at 20 degrees C, the intrinsic binding constants for 1 and 2 are (4.6+/-0.2)x10(5) and (2.3+/-0.3)x10(4) mol(-1) dm(3), respectively. Results of DNA-binding reactions revealed that 1 and 2 preferentially bind to the AT sequence of duplex DNA. Intercalation is the preferred binding mode for 2, whereas both intercalation and minor-groove binding are observed for 1. Complex 1 is cytotoxic against a number of carcinoma cell lines, including KB-3-1, CNE-3, and HepG2, and remains potent against multidrug- or cisplatin-resistant KB-V-1 and CNE1 cell lines, for which the resistance ratios are 1.6 and 1.5, respectively. Importantly, 1 is almost an order of magnitude less toxic to the normal cell line CCD-19Lu (IC(50)=176+/-1.7 microM) and it selectively induced apoptosis leading to cancer cell death with less than 5 % detectable necrosis.     

Synthesis of a Mimicking Hybrid of Annonaceous Acetogenin with Steroid for Antitumoral Activity Investigation

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Synthesis,Structure Analysis,and Antitumor Activity of （R）-2,4-Dioxo-5-fluoro-l-[1-（methoxycarbonyl） Ethylaminocarbonylmethyl]-1,2,3,4-tetrahydropyrimidine

A new dipeptide compound, （R）-2,4-dioxo-5-fluoro-1-[1-（methoxycarbonyl） ethylaminocarbonylmethyl]-1,2,3, 4-tetrahydropyrimidine （5-FUAPM）, has been synthesized and identified by means of elemental analysis, IR, ^1H NMR and ^13C NMR spectra. The single crystal of compound 5-FUAPMoDMF was also obtained and characterized by DSC-TGA techniques. The crystal belongs to orthorhombic space group P212121 with the cell parameters： a= 0.4740（7） nm, b= 1.923（3） nm, c= 1.9229 nm, a=β=y=90°, V= 1.753 nm^3, Z=4, Dc= 1.312 g/cm^3, Mr=346.32, F（000）=728 and u=0.111 mm^-1. The final R and wR are 0.1378 and 0.2862, respectively. The result of the biological test showed that the compound 5-FUAPM has certain antitumor activities.