Synthesis and Crystal Structures of O‐2′,3′‐Cyclic Cyclopentanone and Cyclohexanone Ketals of the Cytostatic 5‐Fluorouridine

The synthesis of two O‐2′,3′‐cyclic ketals, i.e., 5 and 6 , of the cytostatic 5‐fluorouridine ( 2 ), carrying a cyclopentane and/or a cyclohexane ring, respectively, is described. The novel compounds were characterized by ¹H‐, ¹⁹F‐, and ¹³C‐NMR, and UV spectroscopy, as well as by elemental analyses. Their crystal structures were determined by X‐ray analysis. Both compounds 5 and 6 show an anti‐conformation at the N‐glycosidic bond which is biased from +ac to +ap compared to the parent nucleoside 2 . The sugar puckering is changed from ^2′E to _3′E going along with a reduction of the puckering amplitude τ_m by ca. 10–13° due to the ketalization. The conformation about the sugar exocyclic bond C(4′)? C(5′) of 5 and 6 remains unchanged, i.e., g⁺, compared with compound 2 .     

Comparative study on the excretion of vitexin‐4′′‐O‐glucoside in mice after oral and intravenous administration by using HPLC

The aim of the present study was to characterize the excretion of pure vitexin‐4”‐O‐glucoside (VOG) in mice following oral and intravenous administration at a dose of 30 mg/kg. A sensitive and specific HPLC method with hespridin as internal standard, a Diamonsil C₁₈ column protected with a KR C₁₈ guard column and a mixture consisting of methanol–acetonitrile–tetrahydrofuran–0.1% glacial acetic acid (6:2:18:74, v/v/v/v) as mobile phase was developed and validated for quantitative analysis in biological samples. VOG could be excreted as prototype in excreta including urine and feces after both routes of administration, and the cumulative excretion of VOG was 24.31 ± 11.10% (17.97 ± 5.59% in urinary excretion; 6.34 ± 5.51% in fecal excretion) following oral dosing and 5.66 ± 3.94% (4.78 ± 3.13% in urinary excretion; 0.88 ± 0.81% in fecal excretion) following intravenous dosing. The results showed that the elimination of VOG after the two routes was fairly low, which meant that VOG was metabolized as other forms and the elimination after oral dosing was almost 4.3‐fold that after intravenous dosing. For both routes of administration, VOG excreted as prototype in urine was much more than that in feces, nearly 2.83‐fold for oral administration and 5.43‐fold for intravenous administration, which should be attributed to enterohepatic circulation. Taken together, renal excretion was the dominant path of elimination of VOG for oral and intravenous administration in mice and biliary excretion contributed less. Copyright © 2013 John Wiley & Sons, Ltd.     

Structural and theoretical characterization of a new twisted 4′‐substituted terpyridine compound: 4′‐(isoquinolin‐4‐yl)‐2,2′:6′,2′′‐terpyridine

4′‐Substituted derivatives of 2,2′:6′,2′′‐terpyridine with N‐containing heteroaromatic substituents, such as pyridyl groups, might be able to coordinate metal centres through the extra N‐donor atom, in addition to the chelating terpyridine N atoms. The incorporation of these peripheral N‐donor sites would also allow for the diversification of the types of noncovalent interactions present, such as hydrogen bonding and π–π stacking. The title compound, C₂₄H₁₆N₄, consists of a 2,2′:6′,2′′‐terpyridine nucleus (tpy), with a pendant isoquinoline group (isq) bound at the central pyridine (py) ring. The tpy nucleus deviates slightly from planarity, with interplanar angles between the lateral and central py rings in the range 2.24 (7)–7.90 (7)°, while the isq group is rotated significantly [by 46.57 (6)°] out of this planar scheme, associated with a short H_tpy…H_isq contact of 2.32 Å. There are no strong noncovalent interactions in the structure, the main ones being of the π–π and C—H…π types, giving rise to columnar arrays along [001], further linked by C—H…N hydrogen bonds into a three‐dimensional supramolecular structure. An Atoms In Molecules (AIM) analysis of the noncovalent interactions provided illuminating results, and while confirming the bonding character for all those interactions unquestionable from a geometrical point of view, it also provided answers for some cases where geometric parameters are not informative, in particular, the short H_tpy…H_isq contact of 2.32 Å to which AIM ascribed an attractive character.     

Total Synthesis of 4′′‐O‐Acetylmananthoside B Part II: Synthesis of the Disaccharide Fragment

A disaccharide compound, p‐methoxyphenyl 2,3,4‐tri‐O‐benzyl‐β‐L‐arabinopyranosyl‐(1→6)‐2‐O‐benzyl‐3,4‐di‐O‐acetyl‐β‐D‐galactopyranoside ( 17 ), was successfully synthesized from two monosaccharides L‐arabinose and D‐galactose and fully characterized. This compound can be used to build a natural product 4″‐O‐acetylmanan thoside B, which was isolated from the leaves and stems of a kind of Vietnamese Acanthaceae Justicia patentiflora.     

A Novel,One‐Pot Four‐Component Route to 2′‐Thioxo‐2′,3′‐dihydrospiro[indole‐3,6′‐[1,3]thiazin]‐2‐one Derivatives

An efficient route to 2′,3′‐dihydro‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives is described. It involves the reaction of isatine, 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one, and different amines in the presence of CS₂ in dry MeOH at reflux (Scheme 1). The alkyl carbamodithioate, which results from the addition of the amine to CS₂, is added to the α,β‐unsaturated ketone, resulting from the reaction between 1‐phenyl‐2‐(1,1,1‐triphenyl‐λ⁵‐phosphanylidene)ethan‐1‐one and isatine, to produce the 3′‐alkyl‐2′,3′‐dihydro‐4′‐phenyl‐2′‐thioxospiro[indole‐3,6′‐[1,3]thiazin]‐2(1H)‐one derivatives in excellent yields (Scheme 2). Their structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses.     

Proton Nuclear Magnetic Resonance Measurements of 2′-Aminodeoxyuridylyl-3′,5′-Deoxyuridine

A dideoxyribonucleotide, 2′-amino-2′-deoxyuridylyl 3′,5′-deoxyuridine, containing an unsual base (2′-amino-2′-deoxyuridine) that isresistant to nucleases was investigated by ′H NMR. The pK_a of the protonation of the amino group (5.8) was determined by profiles of chemical shifts of protons in the vicinity of amino group versus pH. However, protonation of the amino group has little effect on the conformation of the dimer, assumed to be B-form DNA. This conclusion is drawn from the chemical shift data and coupling constants of H₁-H₂. Thus, 2′-amino-2′-deoxyuridine can be used in antisense and anticode oligonucleotides.     

Validated LC‐MS/MS method for the simultaneous determination of hyperoside and 2′′–O‐galloylhyperin in rat plasma: application to a pharmacokinetic study in rats

An LC‐MS/MS method was developed for the first time to simultaneously determine hyperoside and 2′′–O‐galloylhyperin, two major components in Pyrola calliantha extract, in rat plasma. Following extraction by one‐step protein precipitation with methanol, the analytes were separated on a Venusil MP‐C₁₈ column within 2 min, using methanol–water–formic acid (50:50:0.1, v/v/v) as the mobile phase at a flow rate of 0.4 mL/min. Detection was performed on electrospray negative ionization mass spectrometry by multiple‐reaction monitoring of the transitions of 2′′–O‐galloylhyperin at m/z 615.1 → 301.0, of hyperoside at m/z 463.1 → 300.1, and of internal standard at m/z 415.1 → 295.1. The limits of quantification were 2 ng/mL for both hyperoside and 2′′–O‐galloylhyperin. The precisions were <13.1%, and the accuracies were between ?9.1 and 5.5% for both compounds. The method was successfully applied in pharmacokinetic studies following intravenous administration of the total flavonoids of P. calliantha extract in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and characterization of di‐n‐butyltin(IV) complexes with 4′/2′‐nitrobiphenyl‐2‐carboxylic acids: X‐ray crystal structures of [{(n‐C4H9)2Sn(OCOC12H8NO2−4′)}2O]2 and (n‐C4H9)2Sn{OCOC12H8NO2−4′}2

Reactions of di‐n‐butyltin(IV) oxide with 4′/2′‐nitrobiphenyl‐2‐carboxylic acids in 1 : 1 and 1 : 2 stoichiometry yield complexes [{(n‐C₄H₉)₂Sn(OCOC₁₂H₈NO₂?4′/2′)}₂O]₂ ( 1 and 2 ) and (n‐C₄H₉)₂Sn(OCOC₁₂H₈NO₂?4′/2′)₂ ( 3 and 4 ) respectively. These compounds were characterized by elemental analysis, IR and NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy. The IR spectra of these compounds indicate the presence of anisobidentate carboxylate groups and non‐linear C? Sn? C bonds. From the chemical shifts δ (¹¹⁹Sn) and the coupling constants ¹J(¹³C, ¹¹⁹Sn), the coordination number of the tin atom and the geometry of its coordination sphere have been suggested. [{(n‐C₄H₉)₂Sn(OCOC₁₂H₈NO₂?4′)}₂O]₂ ( 1 ) exhibits a dimeric structure containing distannoxane units with two types of tin atom with essentially identical geometry. To a first approximation, the tin atoms appear to be pentacoordinated with distorted trigonal bipyramidal geometry. However, each type of tin atom is further subjected to a sixth weaker interaction and may be described as having a capped trigonal bipyramidal structure. The diffraction study of the complex (n‐C₄H₉)₂Sn(OCOC₁₂H₈NO₂?4′)₂ ( 3 ) shows a six–coordinate tin in a distorted octahedral frame containing bidentate asymmetric chelating carboxylate groups, with the n‐Bu groups trans to each other. The n‐Bu? Sn? n‐Bu angle is 152.8° and the Sn? O distances are 2.108(4) and 2.493(5) Å. The oxygen atom of the nitro group of the ligand does not participate in bonding to the tin atom in 1 and 3 . Crystals of 1 are triclinic with space group P1 and of that of 3 have orthorhombic space group Pnna. Copyright © 2003 John Wiley & Sons, Ltd.     

One‐dimensional CuII coordination polymers containing C2h‐symmetric 1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylate linkers

Two new one‐dimensional Cu^II coordination polymers (CPs) containing the C_2h‐symmetric terphenyl‐based dicarboxylate linker 1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylate (3,3′‐TPDC), namely catena‐poly[[bis(dimethylamine‐κN)copper(II)]‐μ‐1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylato‐κ⁴O,O′:O′′:O′′′] monohydrate], {[Cu(C₂₀H₁₂O₄)(C₂H₇N)₂]·H₂O}_n, (I), and catena‐poly[[aquabis(dimethylamine‐κN)copper(II)]‐μ‐1,1′:4′,1′′‐terphenyl‐3,3′‐dicarboxylato‐κ²O³:O^3′] monohydrate], {[Cu(C₂₀H₁₂O₄)(C₂H₇N)₂(H₂O)]·H₂O}_n, (II), were both obtained from two different methods of preparation: one reaction was performed in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO) as a potential pillar ligand and the other was carried out in the absence of the DABCO pillar. Both reactions afforded crystals of different colours, i.e. violet plates for (I) and blue needles for (II), both of which were analysed by X‐ray crystallography. The 3,3′‐TPDC bridging ligands coordinate the Cu^II ions in asymmetric chelating modes in (I) and in monodenate binding modes in (II), forming one‐dimensional chains in each case. Both coordination polymers contain two coordinated dimethylamine ligands in mutually trans positions, and there is an additional aqua ligand in (II). The solvent water molecules are involved in hydrogen bonds between the one‐dimensional coordination polymer chains, forming a two‐dimensional network in (I) and a three‐dimensional network in (II).     

A comparative study of the electrospray ionization response of β‐O‐4′ lignin model compounds

Electrospray ionization mass spectrometry has recently become the technique of choice for rapid characterization of lignin degradation products. However, the fundamental question of the relationship between lignin structure and ionization efficiency has not been explored. In this work, we studied the electrospray ionization response of five structurally similar β‐O‐4′ model lignin compounds using lithium cationization in the positive electrospray ionization mode. The studied compounds have the same β‐O‐4′ backbone structure but differ at the α‐position by increasing nonpolar side chains. Our results show a correlation between the ionization response and the length of the nonpolar side chain, with analytes having the longest side chain recording the highest ESI response in the full scan mode. Factors affecting the formation of analyte ions and analyte cluster ions were also studied. We have shown for the first time in this work that the introduction of a nonpolar group onto a β‐O‐4′ lignin compound can increase the lithium cationization ESI response in the positive ion mode.     

Masking of Lewis acidity trends in the solid‐state structures of trichlorido‐ and tribromido(2,2′:6′,2′′‐terpyridine‐κ3N,N′,N′′)gallium(III)

The molecular structures of trichlorido(2,2′:6′,2′′‐terpyridine‐κ³N,N′,N′′)gallium(III), [GaCl₃(C₁₅H₁₁N₃)], and tribromido(2,2′:6′,2′′‐terpyridine‐κ³N,N′,N′′)gallium(III), [GaBr₃(C₁₅H₁₁N₃)], are isostructural, with the Ga^III atom displaying an octahedral geometry. It is shown that the Ga—N distances in the two complexes are the same within experimental error, in contrast to expected bond lengthening in the bromide complex due to the lower Lewis acidity of GaBr₃. Thus, masking of the Lewis acidity trends in the solid state is observed not only for complexes of group 13 metal halides with monodentate ligands but for complexes with the polydentate 2,2′:6′,2′′‐terpyridine donor as well.     

Pharmacokinetics of 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐D‐glucoside in rat using ultra‐performance LC‐quadrupole TOF‐MS

2,3,5,4′‐Tetrahydroxystilbene‐2‐O‐β‐D‐glucoside (THSG) from Polygoni multiflori has been demonstrated to possess a variety of pharmacological activities, including antioxidant, anti‐inflammatory and hepatoprotective activities. Ultra‐performance LC‐quadrupole TOF‐MS with MS Elevated Energy data collection technique and rapid resolution LC with diode array detection and ESI multistage MSⁿ methods were developed for the pharmacokinetics, tissue distribution, metabolism, and excretion studies of THSG in rats following a single intravenous or oral dose. The three metabolites were identified by rapid resolution LC‐MSⁿ. The concentrations of the THSG in rat plasma, bile, urine, feces, or tissue samples were determined by ultra‐performance LC‐MS. The results showed that THSG was rapidly distributed and eliminated from rat plasma. After the intravenous administration, THSG was mainly distributing in the liver, heart, and lung. For the rat, the major distribution tissues after oral administration were heart, kidney, liver, and lung. There was no long‐term storage of THSG in rat tissues. Total recoveries of THSG within 24 h were low (0.1% in bile, 0.007% in urine, and 0.063% in feces) and THSG was excreted mainly in the forms of metabolites, which may resulted from biotransformation in the liver.     

Nucleosides 4: Synthesis of 2′,3′-Didehydro-2′,3′-dideoxydoridosine and 2′,3′-Dideoxydoridosine as Potential Antihypertensive Agents

To measure the hydrophobic character of the ribose moiety of doridosine on the adenosine receptors, 2′,3′-didehydro-2′,3′-dideoxydoridosine (2) and 2′,3′-dideoxydoridosine (3) were prepared. Initial treatment of doridosine with N,N-dimethylformamide diethylacetal, and subsequently with tert-butyldimethylsilyl chloride gave 5. Compound 5 was then reacted with 1,1′-thiocarbonyldiimidazole and the resulting thionocarbonate 6 was heated with triethyl phosphite at 135°C to afford 7. Treatment of compound 7 with tetrabutylammonium fluoride and methanolic ammonia furnished compound 2 in good yield. Compound 2 was subjected to catalytic hydrogenation affording compound 3 in 85% yield.     

Building Functionality into 4′‐Hydrazone Derivatives of 2,2′: 6′,2″‐Terpyridine

The syntheses of the five 2,2′: 6′,2″‐terpyridine (tpy) ligands 5 – 9 functionalized in the 4′‐position with a hydrazone substituent RR′C?N? NH (R=R′=Me; R=H, R′=4‐BrC₆H₄, 4‐O₂NC₆H₄, 4‐MeOC₆H₄, or 3,5‐(MeO)₂C₆H₃) are described. Protonation of the tpy domain of the ligands is facile. Solution behaviour has been studied by NMR and electronic spectroscopies. Representative structural data are presented for neutral and monoprotonated ligands, and illustrate that H‐bonding involving the formal amine NH unit is a dominant structural motif in all cases.     

Two Bulky Conjugated 4′‐(4‐Hydroxyphenyl)‐4,2′:6′,4′′‐terpyridine‐based Layered Complexes: Synthesis,Structure, and Photocatalytic Hydrogen Evolution Activity

Two new layered complexes with the formulas of {[Cu(H₂O)(HL)₂Cl](NO₃)}_n ( 1 ) and {[Cu(H₂O)₂(HL)₂](NO₃)₂}_n ( 2 ) were solvothermally synthesized by the reactions of the bulky conjugated 4′‐(4‐hydroxyphenyl)‐4,2′:6′,4′′‐terpyridine ligand (HL) with different Cu^II salts, which were further used as photocatalysts to achieve hydrogen production from water splitting. Single‐crystal structural analyses reveal that both complexes feature coplanar (4 4) layers with different connection manners between the HL extended Z‐shaped chains. More interestingly, 1 possessing more negative conduction band potential and higher structural stability exhibits a large hydrogen production rate of 2.43 mmol · g^–1 · h^–1, which is four times higher than that of 2 . Thus, the Cu^II‐based coordination polymers modified by the bulky conjugated organic ligand can become potentially promising non‐Pt photocatalysts for hydrogen production from water splitting.     

Improved conditions for fluorescent staining of proteins with 4,4′‐dianilino‐1,1′‐binaphthyl‐5,5′‐disulfonic acid in SDS‐PAGE

A simple and sensitive fluorescent staining method for the detection of proteins in SDS‐PAGE, namely IB (improved 4,4′‐dianilino‐1,1′‐binaphthyl‐5,5′‐disulfonic acid) stain, is described. Non‐covalent hydrophobic probe 4,4′‐dianilino‐1,1′‐binaphthyl‐5,5′‐disulfonic acid was applied as a fluorescent dye, which can bind to hydrophobic sites in proteins non‐specifically. As low as 1 ng of protein band can be detected briefly by 30 min washing followed by 15 min staining without the aiding of stop or destaining step. The sensitivity of the new presented protocol is similar to that of SYPRO Ruby, which has been widely accepted in proteomic research. Comparative analysis of the MS compatibility of IB stain and SYPRO Ruby stain allowed us to address that IB stain is compatible with the downstream of protein identification by PMF.     

Iodine‐Catalyzed Synthesis of Spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones under Mild Conditions

The I₂‐catalyzed preparation of spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones from 2‐aminobenzohydrazide and isatins in MeCN at room temperature in good‐to‐excellent yields is described. The structure of 3 was corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS data). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Synthesis and Anti‐HIV Activity of Triazolo‐Fused 2′,3′‐Cyclic Nucleoside Analogs Prepared by an Intramolecular Huisgen 1,3‐Dipolar Cycloaddition

Triazolo‐fused 2′,3′‐cyclic nucleoside analogs were synthesized by an intramolecular 1,3‐dipolar cycloaddition of nucleoside‐derived azido alkynes in a regio‐ and stereospecific manner. The uracil base in these target compounds was successfully transformed to the corresponding cytosine. The synthesized compounds were examined in a MAGI assay for their anti‐HIV activities, and in a H9 T lymphocytes assay for their cell toxicities.