新型取代苯甲胺葡萄糖氮苷的合成及其抗缺氧活性

以取代苯甲醛(1a~1s)为原料,通过三条路线［A:1a~1o为起始原料,经硼氢化钠还原和溴代反应制得苄基溴衍生物(3a~3o); 3a~3f与邻苯丁二酰亚胺经Gabriel反应制得N-苯甲基邻苯丁二酰亚胺衍生物(4a~4f); 4a~4f与水合肼反应后与D-吡喃葡萄糖反应合成了N-β-D吡喃葡萄糖苯甲胺类化合物(6a~6f)。 B: 3g~3o与全乙酰化D-吡喃葡萄糖胺反应制得全乙酰化葡萄糖氮苷5g~5o; 5g~5o在MeONa-MeOH中脱除乙酰基合成了6g~6o。 C: 1p~1s与全乙酰化D-吡喃葡萄糖胺反应制得全乙酰化葡萄糖氮苷5p~5s; 5p~5s经MeONa-MeOH脱除乙酰基合成了6p~6s］合成了19个取代苯甲胺N-β-D吡喃葡萄糖氮苷类似物(6a~6s,其中6a, 6b, 6e, 6f, 6j, 6n~6q, 6s为新化合物),其结构经¹H NMR和ESI-MS表征。采用MTT法研究了6a~6s对缺氧内皮细胞代谢活力的影响。结果表明： 6a, 6g, 6h和6l的抗缺氧活性优于红景天苷。     

The direct synthesis of 6-amino-6-deoxyaldonic acids as monomers for the preparation of polyhydroxylated nylon 6

6-Azido-6-deoxy-d-galactitol and d-mannitol were obtained quantitatively via the reduction of the corresponding 6-azido-6-deoxy-d-hexono-1,4-lactones, and 6-azido-6-deoxy-d-glucitol was obtained by the reduction of 6-azido-6-deoxyglucose in good yields. The reduction of monoazidodeoxyhexitols by catalytic hydrogenation gave the monoaminohexitol analogues in 95–98% yields. Oxidation of these afforded the corresponding 6-amino-6-deoxy-d-aldonic acids in moderate yields. Alternatively, saponification of 6-azido-6-deoxy-d-hexonolactones gave 6-azido-6-deoxyaldonic acid salts which, after reduction followed by neutralization, led to the expected compounds in 82–88% overall yields.     

Synthesis, structure, and dynamics of six-membered metallacoronands and metallodendrimers of iron and indium

In the reaction of the N-substituted diethanolamines (H(2)L(1-3)) (1-3) with calcium hydride followed by addition of iron(III) or indium(III) chloride, the iron wheels [Fe(6)Cl(6)(L(1))(6)] (4) and [Fe(6)Cl(6)(L(2))(6)] (6) or indium wheels [In(6)Cl(6)(L(1))(6)] (5), [In(6)Cl(6)(L(2))(6)] (8) and [In(6)Cl(6)(L(3))(6)] (9) were formed in excellent yields. Exchange of the chloride ions of 6 by thiocyanate ions afforded [Fe(6)(SCN)(6)(L(2))(6)] (7). Whereas the structures of 4, 5 and 7 were determined unequivocally by single-crystal X-ray analyses, complexes 8 and 9 were characterised by NMR spectroscopy. Contrary to what is normally presumed, the scaffolds of six-membered metallic wheels are not generally rigid, but rather undergo nondissociative topomerisation processes. This was shown by variable temperature (VT) (1)H NMR spectroscopy for the indium wheel [In(6)Cl(6)(L(1))(6)] (5) and is highlighted for the enantiotopomerisation of one indium centre [ 1/6[S(6)-5]<==>[1/6[S(6)-5']]. The self-assembly of metallic wheels, starting from diethanolamine dendrons, is an efficient strategy for the convergent synthesis of metallodendrimers.     

New 2-methyl-6-alkylamino-5,8-quinolinequinones and 1,2,3,4-tetrahydro derivatives

The syntheses of six new 2-methyl-6-alkylamino-5,8-quinolinequinones, three 1,2,3,4-tetrahydro-5,8-quinolinequinones, and 7-(2′,6′,10′-trimethylundecyl)-6-hydroxy-5,8-quinolinequinone are described as potential antimetabolites of coenzyme Q and as potential antimalarial agents. The six 2-methyl-6-alkylamino-5,8-quinolinequinones were prepared by a six-step synthesis. 2-Methyl-6-methoxy-8-nitroquinoline was prepared from 2-nitro-4-methoxyaniline and crotonaldehyde by a Skraup reaction. Raney nickel reduction gave 2-methyl-6-metboxy-8-aminoquinoline, which upon diazotization followed by dithionite reduction yielded 2-methyl-6-methoxy-5,8-diaminoquinoline. Subsequent dichromate oxidation gave 2-methyl-6-methoxy-5,8-quinolinequinone, which yielded the corresponding 2-methyl-6-alkylamino-5,8-quinolinequinone in good yield when treated with the appropriate alkylamine. The telrahydro-5,8-quinolinequinones were prepared by catalytic hydrogenation of the appropriate 5,8-quinolinequinones at elevated H₂ pressure followed by air oxidation of the reduction product. 7-(2′,6′,10′-Trimethylundecyl)-6-hydroxy-5,8-quinolinequinone was synthesized by radical alkylation of 6-hydroxy-5,8-quinolinequinone by thermal decomposition of di-3,7,11-trimethyldodecanoyl peroxide, which was prepared by a multistep procedure from farnesol. Of the five new 2-methyl-6-alkylamino-5,8-quinoline-quinones tested against P. berghei in mice (blood schizonticidal test), only 2-methyl-6-cycloheptylamino-5,8-quinolinequinone was active (T-C = 6.1 at 320 mg./kg.). Both 7-(2′,6′,10′-trimelhytundecyl)-6-hydroxy-5,8-quinolinequinone and the tetrahydro derivatives were inactive in this same test system.     

Synthesis of 9-(2-fluorobenzyl)-6-methylamino-9H-purine

Synthesis of 9-(2-fluorobenzyl)-6-methylamino-9H-purine ( 1 ) from nine different precursors is reported. Compound 1 was prepared by methylamination of 6-chloro-9-(2-fluorobenzyl)-9H-purine ( 4 ), by alkylation of 6-methylaminepurine ( 5 ) or form 9-(2-fluorobenzyl)-1-methyladeninium iodide ( 8 ) via the Dimroth rearrangement. Selective 2-step methylation of 6-aminopurine 6 was accomplished by hydride reduction of 6-formamidopurine 9 , 6-dimethylaminomethyleneaminopurine 10 or 6-phenylthiomethyl purine 11 to give 1. Compound 1 was also prepared by dethiation or reductive dechlorination of 2-methylthiopurine 16 or 8-chloropurine 19 , respectively, or by hydrolysis of 6-N-methylformamidopurine 12 , which was prepared from 6-dimethylaminopurine 13 by selective oxidation.     

Studies on the synthesis of compounds related to adenosine 3',5'-cyclic phosphate. VII. Synthesis and cardiac effects of N6,N6-dialkyl adenosine 3',5'-cyclic phosphates

A series of novel N6,N6-dialkyl adenosine 3',5'-cyclic phosphates N6,N6-dialkyl cAMPs) was synthesized from 2'-O-p-toluenesulfonyl cAMP (2'-O-tosyl cAMP, 2) and tested for inotropic and chronotropic activities in vitro. Treatment of 2 with excess alkyl halides and sodium hydride followed by detosylation with aqueous NaOH readily gave N6,N6-dialkyl cAMPs (3) in good yields. Various N6,N6-dialkyl cAMPs having different alkyl groups at the N6-position (9-12) were prepared by alkylation followed by detosylation of N6-alkyl-2'-O-tosyl cAMPs (4) which were obtained by the reductive alkylation of 2 with aldehydes in the presence of sodium cyanoborohydride in acetic acid or tosylation of N6-methyl cAMP. The mechanism of the detosylation is briefly discussed. Among the N6,N6-dialkylated derivatives, N6,N6-dipentyl (3f) and N6-ethyl-N6-heptyl (10e) derivatives were found to exhibit a potent positive inotropic effect and a weak positive chronotropic effect. The structure-activity relationships for the position and the length of alkyl residue are discussed.     

Purine N-oxides: XXXVII. Derivatives from 6-chloropurine 3-oxide

Interaction of 6-chloropurine 3-oxide with several amines led to 6-substituted purine 3-oxides. 6-Chloropurine 3-oxide and selenourea gave 6-selenopurine 3-oxide. 6-Mereaptopurine 3-oxide, prepared from the 6-chloro derivative and ammonium dithioearbonate, was transformed with chlorine and hydrogen fluoride into 6-purinesulfonyl fluoride 3-oxide which upon ammonolysis afforded purine-6-sulfonamide 3-oxide. Methanelhiol and 6-ehloropurint: 3-oxide yielded the known 6-methylthiopurine 3-oxide, which by treatment with chlorine was oxidized to 6-methyl-sulfonylpurine 3-oxide. Reaction of the latter with hydroxylamine led to an improved synthesis of 6-hydroxylaminopurine 3-oxide, which by interaction with manganese dioxide was transformed into 6-nitrosopurine 3-oxide.     

C~6~0与二氯卡宾环加成反应机理的理论研究

用半经验AM1方法研究了C~6~0与单态二氯卡宾环加成反应的反应机理。采用Berny梯度法优化得到反应的过渡态,并进行了振动分析确认。计算结果表明：二氯卡宾在C~6~0的6-6或6-5键上的加成反应均分两步进行,第一步反应物经(类)过渡态Ⅰ生成中间配合物,第二步由中间配合物经过渡态Ⅱ变为产物。6-6加成反应的活化势垒较6-5加成反应的低121kJ·mol^-^1,从反应机理和动力学角度解释了6-6加成优于6-5加成的原因。     

The Effects of Serum on Cellular Uptake and Phototoxicity of Mono-L-Aspartyl Chlorin e6 (NPe6) In Vitro

Abstract— Previous reports showed that the photosensitizer mono- l -aspartyl chlorin e6 (NPe6) binds to serum proteins. However, the influence of this binding on the cellular uptake and photodynamic therapy (PDT) phototoxicity of NPe6 is still undefined. In this paper, we studied how serum in medium affected the P388 cellular uptake and PDT phototoxicity of NPe6 in vitro. This was assessed by (1) detection of the red shift (654 nm Q band peak of absorption) induced by protein binding NPe6; (2) detection of intracellular concentration of NPe6 by HPLC and (3) measurements of the cell survival ratio after PDT by MTT assay. The 654 nm Q band peak of NPe6 shifted to 665 nm after binding of NPe6 and serum proteins. The protein-bound NPe6 cannot be uptaken by cells, thus there was no PDT phototoxicity. Nevertheless, phototoxicity recovered when the concentration of NPe6 excessed the serum protein binding ability or there was free serum protein in the medium. These data suggested that the cellular uptake of NPe6 is inhibited by serum components in the medium, and that only free NPe6 is accumulated by P388 cells even during relatively long incubations. The cytotoxicity of PDT mainly depends on the free NPe6 level in the medium.     

Preparation of three positional isomers of diglucosyl-cyclomaltohexaose.

Three positional isomers of diglucosyl-cyclomaltohexaose (diglucosyl-cG6) were chemically synthesized via 6(1),6(2)-, 6(1),6(3)-, and 6(1),6(4)-di-O-(TERT-butyldimethylsilyl)-cG6S (1, 2, and 3) prepared regiospecifically. Glucosylation of bis(2,3-di-O-acetyl)tetrakis(2,3,6-tri-O-acetyl)-CG6S obtained from the three regioisomeric compounds 1, 2, and 3 with 2,3,4,6-tetra-O-benzyl-1-O-trichloroacetimidoyl-alpha-D-glucopyran ose, followed by debenzylation and then deacetylation, afforded 6(1),6(2)-, 6(1),6(3)-, and 6(1),6(4)-di-O-(alpha-D-glucopyranosyl)-cG6S (10, 11, and 12) together with configurational isomers. The desired compounds 10, 11, and 12 containing two (1----6)-alpha-linkages were isolated from the mixtures of their configurational isomers by high performance liquid chromatography. The three diglucosyl-cG6S synthesized chemically were used as authentic samples to identify the components in a mixture of diglucosyl-cG6S produced by an enzymatic process.     

Ionic conductivity in crystalline PEO6:Li(AsF6)1-x(SbF6)x

The ionic conductivity of PEO6:LiXF6 (X = As, Sb) complexes may be raised by over an order of magnitude by forming solid solutions of PEO6:Li(AsF6)1-x(SbF6)x.     

Encapsulation of cationic ruthenium complexes into a chiral self-assembled cage

A chiral supramolecular assembly encapsulates the two cationic ruthenium sandwich complexes [CpRu(eta(6)-C(6)H(6))](+) and [CpRu(p-cymene)](+). The host-guest complexes K(11)[CpRu(eta(6)-C(6)H(6)) subset Ga(4)L(6)] (2) and K(11)[CpRu(p-cymene) subset Ga(4)L(6)] (3) were characterized by one- and two-dimensional NMR techniques as well as by electrospray mass spectrometry. Encapsulation of the prochiral complex [CpRu(p-cymene)](+) by the chiral host renders enantiotopic protons diastereotopic as evidenced by (1)H NMR spectroscopy.     

Modulation of heme redox potential in the cytochrome c6 family

Cytochrome c6A is a unique dithio-cytochrome of green algae and plants. It has a very similar core structure to that of bacterial and algal cytochromes c6 but is unable to fulfill the same function of transferring electrons from cytochrome f to photosystem I. A key feature is that its heme midpoint potential is more than 200 mV below that of cytochrome c6 despite having His and Met as axial heme-iron ligands. To identify the molecular origins of the difference in potential, the structure of cytochrome c6 from the cyanobacterium Phormidium laminosum has been determined by X-ray crystallography and compared with the known structure of cytochrome c6A. One salient difference of the heme pockets is that a highly conserved Gln (Q51) in cytochrome c6 is replaced by Val (V52) in c6A. Using protein film voltammetry, we found that swapping these residues raised the c6A potential by +109 mV and decreased that of c6 by almost the same extent, -100 mV. X-ray crystallography of the V52Q protein showed that the Gln residue adopts the same configuration relative to the heme as in cytochrome c6 and we propose that this stereochemistry destabilizes the oxidized form of the heme. Consequently, replacement of Gln by Val was probably a key step in the evolution of cytochrome c6A from cytochrome c6, inhibiting reduction by the cytochrome b6f complex and facilitating establishment of a new function.     

Modular and practical synthesis of 6-substituted pyridin-3-yl C-nucleosides

A novel modular and practical methodology for preparation of 6-substituted pyridin-3-yl C-nucleosides was developed. The Heck reaction of 2-chloro-5-iodopyridine with a 3'-TBDMS-protected glycal gave a 6-chloropyridin-3-yl nucleoside analogue, which was then desilylated, selectively reduced, and reprotected to give the TBDMS-protected 6-chloropyridin-3-yl C-2'-deoxyribonucleoside as a pure beta-anomer in a total yield of 39% over four steps. This key intermediate was then subjected to a series of palladium-catalyzed cross-coupling reactions, aminations, and alkoxylations to give a series of protected 1beta-(6-alkyl-, 6-aryl-, 6-hetaryl, 6-amino-, and 6-tert-butoxypyridin-3-yl)-2'-deoxyribonucleosides. 6-Unsubstituted pyridin-3-yl C-nucleoside was prepared by catalytic hydrogenation of the chloro derivative and 6-oxopyridine C-nucleoside by treatment of the 6-tert-butoxy derivative with TFA. Deprotection of all the silylated nucleosides by Et3N.3HF gave a series of free C-nucleosides (10 examples).     

Synthesis of chromium(0) and molybdenum(0) bis (eta(6)-arene) derivatives and their monoelectronic oxidation to [M(eta(6)-arene)(2)](+) cations

M(eta(6)-arene)(2) species (M = Cr, arene = 1,3,5-Me(3)C(6)H(3); M = Mo, arene = 1,3,5-Me(3)C(6)H(3), 1,3,5-(i)Pr(3)C(6)H(3)), have been prepared by a modified Fischer-Hafner synthesis or by metal vapour techniques. The reaction of Cr(eta(6)-1,3,5-Me(3)C(6)H(3))(2) with the fulvene derivatives pentacarbomethoxycyclopentadiene (pcmcpH), 1-benzoyl-6-hydroxy-6-phenylfulvene (dbcpH), or 1-benzoyl-3-nitro-6-hydroxy-6-phenylfulvene (dbncpH) proceeds with evolution of dihydrogen and formation of the ionic derivatives [Cr(eta(6)-1,3,5-Me(3)C(6)H(3))(2)][E], where E = pcmcp, dbcp, or dbncp. Mo(eta(6)-arene)(2) derivatives (arene = toluene, 1,3,5-Me(3)C(6)H(3), 1,3,5-(i)Pr(3)C(6)H(3)) are oxidized to [Mo(eta(6)-arene)(2)](+) by pcmcpH. The crystal and molecular structures of [M(eta(6)-1,3,5-R(3)C(6)H(3))(2)][pcmcp] (M = Cr, R = Me; M = Mo, R = Me, (i)Pr) have been solved by X-ray single crystal diffraction.     

Mechanistic Insights into the Fluorescence Quenching of Rhodamine 6G by Graphene Oxide

The fluorescence quenching of Rhodamine 6G (R6G) by graphene oxide (GO) was interrogated by R6G fluorescence measurements using a set of controlled GO samples with varied C/O ratios as the quencher.The carbonyl groups on the GO nanosheet turned to play a dominant role in quenching the R6G fluorescence.The quenching in the static regime can be described by the "sphere of action" model.The significant absorption of the R6G fluorescence by the ground-state complex formed between R6G and GO was identified to be responsible for the static quenching.This work offers helpful insights into the fluorescence quenching mechanisms in the R6G/GO system.     

π键及大π键对正电集团和负电集团的作用——分子间引力的选择性

The selectivity of intermolecular force is caused by the special interaction between two adaptable groups on the molecules. π bond and conjugated π bonds such as benzene ring are negative charged groups,which may attract stongly positively charged H groups such as 3H in β-C_6H_6Cl_6, and repulse other ne- gatively charged groups such as-C=O(Q). Our experiments show that the reduced retention time tr of benzene on non- polar β-C_6H_6Cl_6 is much greater than that on polar fixed phases such as CH_3— —NO_2 in gas chromatography and that the het of solvation of β-C_6H_6Cl_6 in benzene is also much greater than that of the polar α-C_6H_6Cl_6 and γ-C_6H_6Cl_6. This can′t be explained by the usual Van de Waals′ force. It results from the selective intermoleccular force....     

富烯与2-吡啶甲基锂及2-喹啉甲基锂的反应: 含氮杂环取代二茂 铁的合成

在四氢呋喃-乙醚溶剂中,6-甲基-2-吡啶甲基锂与6,6-二烷基富烯或6,6-n亚甲基富烯(n=4,5,6)均发生环外双键加成反应。在类似反应条件下,2-喹啉甲基锂与6-甲基-6-乙基富烯或6,6-五亚甲基富烯皆发生加成反应和α-攫氢的竞争反应。用上述反应产生的取代环戊二烯基锂与二氯化铁配位,合成了一系列含氮杂环取代二茂铁衍生物。其结构经^1HNMR,元素分析和MS确证。在该类化合物的质谱裂解中,发现吡啶环对铁原子存在配位作用。     

Unusual coexistence of magnetic and nonmagnetic Mo6 octahedral clusters in a chalcohalide solid solution: synthesis, X-ray diffraction, EPR, and DFT investigations of Cs3Mo6Ii6Ii2-xSeixIa6

The Cs3Mo6Ii6Ii2-xSeixIa6 series has been obtained by a solid-state route. There is evidence for a solid solution between the compositions Cs3Mo6Ii6Ii0.8Sei1.2Ia6 and Cs3Mo6Ii6Ii0.4Sei1.6Ia6 (space group: R3c, Z=6; a=16.7065(4), c=20.5523(4) A, V=4967.8(2) A3 and a=16.6354(3), c=20.5444(4) A, V=4923.7(2) A3, respectively). The structure of this new series is based on magnetic [Mo6Ii6Sei2Ia6]3- and diamagnetic [Mo6Ii7SeiIa6]3- units with 23 and 24 valence electrons per Mo6 cluster, respectively. For a particular x, the structure of Cs3Mo6Ii6Ii2-xSexIa6 is based on a mixture of (x-1) [Mo6Ii6Sei2Ia6]3- with (2-x) [Mo6Ii7SeiIa6]3-. This leads to an average [Mo6Ii6Ii2-xSexIa6]3- ionic unit deduced from single-crystal X-ray diffraction investigations. The two inner positions of the average face-capped [Mo6Ii8-xSeixIa6]3- ionic units (located on the threefold axis of the unit) are randomly occupied by iodine and selenium, whereas the other ligand positions are fully occupied by iodine. Low-temperature electron paramagnetic resonance (EPR) studies reveal a signal split into two components with g||>gperpendicular. The reciprocal double integration intensity of the EPR signal versus T graph reveals a typical Curie law behavior. A density functional theory (DFT) study indicates that occupation of the inner position on the threefold axis by selenium atoms is preferred energetically among the three possible distributions of selenium atoms. The comparison of experimental and theoretical g values confirms the crystallographic analysis and agrees with the axial elongation of the Mo6 cluster within the crystal structure.     

Protective effects of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-hydroxydopamine-induced neuronal cell death

6-Hydroxydopamine (6-OHDA) is a neurotoxin and is commonly used to generate experimental models of Parkinson's disease (PD). In this study, we investigated the signaling molecules involved in the 6-OHDA-induced cell death using a neuronal catecholaminergic cell line (SK-N-SH cells), and the protective effect of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-OHDA-induced neuronal death. 6-OHDA significantly increased levels of reactive oxygen species (ROS), intracellular Ca(2+) ([Ca(2+)](i)), and p38 phosphorylation. In addition, this ROS increase by 6-OHDA was reduced by pretreatment with N-acetylcysteine (NAC), a free radical scavenger, but not by bis-(o-aminophenoxy)-ethane-N,N,N,N-tetraacetic acid (BAPTA), a Ca(2+) chelator. However, the [Ca(2+)](i) increase induced by 6-OHDA was suppressed by NAC. Moreover, pretreatment with NAC or BAPTA significantly prevented the 6-OHDA-induced increases in p38 phosphorylation, Bax/Bcl-2 ratio, and caspase-3 activity. Although 6-OHDA-increased phosphorylation of p38 was prevented by NAC or BAPTA, inhibition of p38 by SB203580 did not suppress ROS, Bax/Bcl-2 ratio, or caspase-3 activity increases, and only partially prevented 6-OHDA-induced cell death, thus demonstrating that p38 activation is a component of a signaling pathway leading to the initiation of 6-OHDA-induced cell death, which acts in parallel with an ROS-Ca(2+)-Bcl-2-caspase-3 pathway. Moreover, fustin not only suppressed 6-OHDA-induced cell death in a concentration-dependent manner but also blocked 6-OHDA-induced increases in ROS, [Ca(2+)](i), Bax/Bcl-2 ratio, caspase-3 activity, and p38 phosphorylation. These results suggest that fustin exerts neuroprotection against 6-OHDA-induced cell death.