5-Alpha- and 5-beta-2-deoxyintegristerone A,a 5-alpha and 5-beta isomer pair of ecdysteroids isolated from the Silene genus

5-Alpha-2-deoxyintegristerone A and 5-beta-2-deoxyintegristerone A were isolated from the aerial parts of Silene italica ssp. nemoralis (Waldst. and Kit.) Nyman using a specific combination of absorption column chromatography, preparative thin-layer chromatography and preparative HPLC. Both normal-phase and reversed-phase modes of HPLC were employed for isolation. Structural elucidation of 5-alpha-2-deoxyintegristerone A was completed by X-ray diffraction. Both 5-alpha-2-deoxyintegristerone A and 5-beta-2-deoxyintegristerone A were firstly isolated from this plant. We propose that 5-alpha-2-deoxyintegristerone A is not an artifact but an integral part of the ecdysteroid spectrum of Silene italica ssp. nemoralis (Waldst. and Kit.) Nyman.     

Synthesis of novel 5-hydroxy-3-alkoxy- and 5-hydroxy-3-alkylthioindole-2-carboxamides

The preparation of several novel 5-hydroxyindole-2-carboxamides is described. A 5-benzyloxyindole ester was elaborated to the 3-bromo, 3-hydroxy, and 3-alkoxy ester intermediates followed by conversion to the amide and debenzylation. A related 5-acetyloxy indole ester was converted to 3-sulfinyl and 3-alkylthio intermediates before simultaneous amidation and removal of the 5-hydroxy protecting group.     

Simultaneous LC-MS-MS Analysis of Capecitabine and its Metabolites (5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine, 5-fluorouracil) After Off-Line SPE from Human Plasma

A new single extraction procedure was developed to isolate capecitabine and its major metabolites (5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine, and 5-fluorouracil) from human plasma. The simultaneous extraction of the four analytes was performed on an Atoll XWP solid phase support. Separation and detection were by liquid chromatography (5 µm Atlantis C₁₈, 150 × 2.1 mm) and Turbospray Mass spectrometry in negative mode. To our knowledge, this report is the first to use these conditions for the simultaneous analysis of capecitabine and its metabolites.     

Synthesis and Characterization of the Chiral Skeleton Cluster [NiRuMo(CO)_5(μ_3-S)(η~5-C_5H_5)(η~5-C_5H_4COCH_3)]

1 INTRODUCTION The chemistry of transition metal cluster has enjoyed an exceptional growth since the mid 1970s[1, 2], especially in recent years the structural and bonding aspects of mixed-metal tetrahedral skeleton clusters have been extensively studied[3]. One important reason is that such chiral cluster can induce an asymmetric catalysis potentially. In our research group, considerable efforts have been directed to the synthesis of chiral tetrahedral clusters containing four different…     

Concise synthesis of 5-methyl-, 5-formyl,and 5-carboxy analogues of 2′-deoxycytidine-5′-triphosphate

We describe a concise and efficient synthesis of 5-methyl-, 5-formyl-, and 5-carboxy-analogues of 2′-deoxycytidine-5′-triphosphate which are well known for their various biological applications. A protection-free one-pot synthesis was used to convert 5-methyl-2′-deoxycytidine into 5-methyl-2′-deoxycytidine-5′-triphosphate in high yield. 5-Formyl-2′-deoxycytidine-5′-triphosphate was obtained upon photosensitized oxidation (UV-A irradiation, λ ∼365 nm) of an aerated aqueous solution of 5-methyl-2′-deoxycytidine-5′-triphosphate with the use of menadione as the photosensitizer. 5-Formyl-2′-deoxycytidine-5′-triphosphate was converted into 5-carboxy-2′-deoxycytidine-5′-triphosphate by using biphasic TEMPO/BAIB oxidation method in high yield.     

Isotachophoretic determination of 2-5A phosphodiesterase

Together with 2-5A synthetase and ribonuclease L, 2-5A phosphodiesterase belongs to the 2-5A system, which plays an important role in the action of interferon. Analytical capillary isotachophoresis was used for the determination of 2-5A phosphodiesterase activity. Enzyme assay was optimized using snake venom phosphodiesterase as a source of 2-5A phosphodiesterase activity. The 2-5A trimer core was used as a substrate. Enzyme activity was determined in time- and concentration-dependent reactions. In addition, 2-5A phosphodiesterase activity was determined in lysates of mononuclear blood cells.     

Comparison of bioactivities of 5-Fluoro, 5-Iodo, 5-Iodovinyl, and 5-fluorovinyl arabinosyl uridines against SR-39 TK-transfected murine prostate cancer cells

A cell survival assay of the four arabinosyl uridine analogs with functionalities of 5-fluoro, 5-fluorovinyl, 5-iodo, and 5-iodovinyl as potential positron-emitter tagged probe for monitoring cancer gene therapy were performed. Cytotoxicities of 5-fluoro-, 5-iodo-, 5-fluorovinyl, and 5-iodovinyl arabinosyl uridines against SR-39 thymidine kinase transfected murine prostate cancer cells have been evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. None of them showed significant bioactivity. A syn conformation derived from intra-hydrogen bonding was suggested for the unfavorable interaction and diminished bioactivity.     

5-烃基-5-对甲苯磺酰氧基丙二酸亚异丙酯的合成

报道了利用羟基(对甲苯磺酰氧基)碘苯与5-烃基丙二酸亚异丙酯的反应合成5-烃基-5-对甲苯磺酰氧基丙二酸亚异丙酯的方法。提出了该反应的可能机理。     

High Performance Liquid Chromato-Graphic Assay For 5-Fluorouracil and 5-Fluorocytosine

Abstract

A high performance liquid chromatographic assay for separating 5-fluorouracil and 5-fluorocytosine in the presence of potential decomposition products urea, barbituric acid, uracil 6-hydroxycytosine, and cytosine was developed.

It was found that ion-pair chromatography using a reversephase C18 column, 0.46 cm i.d. by 15 cm in length, employing gradient elution was satisfactory for separating the various compounds, however, isocratic elution was more appropriate for determining the concentration of the two drugs in the presence of their actual decomposition products.

The mobile phase for isocratic elution was 85% aqueous phosphate buffer pH 2.1 and 15% methanol containing 0.0025 M pentane and heptane sulfonic acid sodium salts delivered at 1.0 mllmin. The eluent was monitored at 254 and 285 nm as all compounds do not absorb strongly at a single wavelength. A linear relationship was obtained for the peak height ratio for both 5-fluorouracil and 5-fluorocytosine against 5-methylcytosine, the internal standard over the range 0.125 to 1.000 × ? 10^?4 M ₀     

High-performance liquid chromatographic analysis of 5-ethylpyrimidines and 5-methylpyrimidines in plasma

A high-performance liquid chromatographic (HPLC) method employing a C18 reversed-phase column, a mobile phase of sodium acetate and methanol, and an ultraviolet detector was developed for the analysis of 5-ethylpyrimidines and 5-methylpyrimidines in plasma. Samples were prepared for HPLC by sequential cation-exchange and anion-exchange column chromatography. Linear standard curves were obtained for samples containing 0.05-50 micrograms/ml 5-ethyl-2'-deoxyuridine and 5-ethyluracil, 0.05-10 micrograms ml 5-(1-hydroxyethyl)uracil, and 0.1-50 micrograms/ml thymidine, thymine and 5-hydroxymethyluracil. Applicability of the method to determination of the kinetics of 5-ethyl-2'-deoxyuridine elimination by the isolated perfused rat liver was demonstrated; clearance of the drug was 1.29 ml/min.     

重组内切纤维素酶Fpendo5A转化三七总皂苷

从嗜热细菌基因组中克隆到1个新的纤维素酶基因,并在大肠杆菌中进行了高效可溶性表达,粗酶液经镍柱亲和层析进行分离纯化.利用快速分离液相色谱-四极杆飞行时间质谱联用仪(RRLC/Q-TOF-MS)对重组内切纤维素酶Fpendo5A转化三七总皂苷的产物结构进行了鉴定,并进一步阐明其转化机制.结果表明,该酶的最适反应温度和pH值分别为80℃和5.5.Fpendo5A能够催化三七总皂苷中的主要皂苷成分,即Ra_1,Rb_1,Rc,Rd和Rg_3的侧链糖基的水解反应,但对于不同的皂苷底物,Fpendo5A选择性催化的侧链糖基类型不同.经鉴定,Fpendo5A转化Ra_1,Rb_1,Rc,Rd和Rg_3的转化产物分别为Rb_2,GypⅩⅦ,CMC_1,F_2和Rh_2.由此可见,Fpendo5A通过水解Rb_1,Rc,Rd和Rg3的C3位的β-(1,2)糖苷键分别生成GypⅩⅦ,CMC1,F2和Rh2.在转化Ra_1时,Fpendo5A通过水解Ra_1的C20位的α-(1,4)木糖苷键生成Rb2.     

Interconversion of the cis-5R,6S- and trans-5R,6R-thymine glycol lesions in duplex DNA

Thymine glycol (Tg), 5,6-dihydroxy-5,6-dihydrothymine, is formed in DNA by the reaction of thymine with reactive oxygen species. The 5R Tg lesion was incorporated site-specifically into 5'-d(G(1)T(2)G(3)C(4)G(5)Tg(6)G(7)T(8)T(9)T(10)G(11)T(12))-3'; Tg = 5R Tg. The Tg-modified oligodeoxynucleotide was annealed with either 5'-d(A(13)C(14)A(15)A(16)A(17)C(18)A(19)C(20)G(21)C(22)A(23)C(24))-3', forming the Tg(6) x A(19) base pair, corresponding to the oxidative damage of thymine in DNA, or 5'-d(A(13)C(14)A(15)A(16)A(17)C(18)G(19)C(20)G(21)C(22)A(23)C(24))-3', forming the mismatched Tg(6) x G(19) base pair, corresponding to the formation of Tg following oxidative damage and deamination of 5-methylcytosine in DNA. At 30 degrees C, the equilibrium ratio of cis-5R,6S:trans-5R,6R epimers was 7:3 for the duplex containing the Tg(6) x A (19) base pair. In contrast, for the duplex containing the Tg(6) x G(19) base pair, the cis-5R,6S:trans-5R,6R equilibrium favored the cis-5R,6S epimer; the level of the trans-5R,6R epimer remained below the level of detection by NMR. The data suggested that Tg disrupted hydrogen bonding interactions, either when placed opposite to A(19) or G(19). Thermodynamic measurements indicated a 13 degrees C reduction of T(m) regardless of whether Tg was placed opposite dG or dA in the complementary strand. Although both pairings increased the free energy of melting by 3 kcal/mol, the melting of the Tg x G pair was more enthalpically favored than was the melting of the Tg x A pair. The observation that the position of the equilibrium between the cis-5R,6S and trans-5R,6R thymine glycol epimers in duplex DNA was affected by the identity of the complementary base extends upon observations that this equilibrium modulates the base excision repair of Tg [Ocampo-Hafalla, M. T.; Altamirano, A.; Basu, A. K.; Chan, M. K.; Ocampo, J. E.; Cummings, A., Jr.; Boorstein, R. J.; Cunningham, R. P.; Teebor, G. W. DNA Repair (Amst) 2006, 5, 444-454].     

Synthesis of 5-benzoyl-5-phenyl- and 5-phenylhydroxymethyl-5-phenylhydantoins as potential anticonvulsants

A series of 5-benzoyl-5-phenyl- and S-phenyl-5-phenylhydroxymethylhydantoins have been synthesized from the reaction of urea, N-monosubstituted ureas and sym-N-N-disubstituted ureas with phenyltriketone hydrate, via a pinacol-pinacolone-type rearrangement mechanism. The compounds were evaluated for anti-convulsant activity in mice.     

Regiospecific Preparation of 5-Acylaminotetralones

A Beckmann Rearrangement/Friedel-Crafts strategy was utilized to prepare 5-amidotetralones in high yield.     

IR and Raman characterization of the zincocenes (eta(5)-C5Me5)2Zn2 and (eta(5)-C5Me5)(eta(1)-C5Me5)Zn

The measured Raman and IR spectra of solid, polycrystalline bis(pentamethylcyclopentadienyl)dizinc, (eta(5)-C5Me5)2Zn2, 1, and bis(pentamethylcyclopentadienyl)monozinc, (eta(5)-C5Me5)(eta(1)-C5Me5)Zn, 8, are reported in some detail. The IR spectra of the vapors of 1 and 8 each trapped in a solid Ar matrix at 12 K confirm the essentially molecular character of the solids. The experimental results have been interpreted with particular reference (i) to the corresponding spectra of (68)Zn-enriched samples of the compounds, and (ii) to the spectra simulated by density functional theory (DFT) calculations at the B3LYP level. The marked differences of structure of 1 and 8 contrast with the relatively close similarity of their vibrational spectra, disparities being revealed only on detailed scrutiny, including the effects of (68)Zn enrichment, and primarily at wavenumbers below 1000 cm(-1). The Zn-Zn stretching motion of 1 features not as a single, well-defined mode identifiable with intense Raman scattering but in several normal modes which respond in varying degrees to (68)Zn substitution. A stretching force constant of 1.42 mdyne A(-1) has been estimated for the Zn-Zn bond of 1.     

New classes of carborane-appended 5-thio-D-glucopyranose derivatives

A series of carborane-appended 5-thio-D-glucopyranose (5-TDGP) derivatives containing one to two 5-TDGP moieties were synthesized via click cycloaddition reaction as well as following the traditional methods. Among the carboranyl-5-TDGP derivatives, the decapitated nido-carboranyl derivative 18 was found to be highly water-soluble and therefore its preliminary biodistribution study was conducted. A comparative biological evaluation of 18 versus its carboranyl-D-glucopyranose analog 19 with human hepatocellular carcinoma cells (SK-Hep1) indicated 5-TDGP to be a better boron carrier than normal D-glucopyranose. The carboranyl-5-TDGP 18 showed a nearly two fold increase in cellular boron accumulation than carboranyl-D-glucopyranose analog 19 over a period of 2 h. The accumulation of both 18 and 19 was found to occur in a temperature dependent manner. The higher accumulation of 18 suggested excellent promise for it to be a candidate for further evaluation as a future BNCT agent.     

A convenient stereoselective synthesis of 5-hydroxy-3-oxoesters and 3-hydroxy-5-oxoesters

A biocatalytic approach was employed for the asymmetric reduction of sterically demanding ketones to prepare 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates. Screening a collection of microorganisms led to the identification of stereocomplementary microbial strains that provide access to both enantiomers of 3-hydroxy-5-oxo-5-phenylpentanoates and 5-hydroxy-3-oxo-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). Moreover, the application of Saccharomyces cerevisiae gave two diastereomers of 3,5-dihydroxy-5-phenylpentanoates with high enantiomeric excess (up to 99% ee). The applicability of the identified strains was demonstrated by transforming the obtained dihydroxy ester into the chemically valuable lactone (4S,6R)-tetrahydro-4-hydroxy-6-phenyl-pyran-2-one.     

The preparation and reduction of 5-cyano-3-indolylketones. Synthesis of 5-cyanotryptamines

The acylation of indoles under acidic conditions has been studied. Stannic chloride was shown to be an effective catalyst for the preparation of some 3-acylindoles, notably 5-cyano-3-indolylketones. The various 5-cyano -3 - indolylketones were reduced with sodium borohydride to yield either the 5-cyano-3-carbinols or 5-cyano-3-alkylindoles. 5-Cyanotryptamines were obtained by reduction of appropriate α-dialkylamino and α-azidoketones. A cleavage reaction of the carbinols involving loss of the 3-side chain to yield 5-cyanoindole is also described.     

Electron-transfer salts of 1,2,3,4,5-pentamethylferrocene, Fe(II)(C5Me5)(C5H5). Structure and magnetic properties of two 1:1 and two 2:3 Fe(C5Me5)(C5H5) electron-transfer salts of tetracyanoethylene

The reaction of Fe(II)(C5Me5)(C5H5), FeCpCp, with percyano acceptors, A [A = C4(CN)6 (hexacyanobutadiene), TCNQF4 (perfluoro-7,7,8,8-tetracyano-p-quinodimethane), and DDQ (2,3-dichloro-5,6-dicyanobenzoquinone)], results in formation of 1:1 charge-transfer salts of [Fe(III)CpCp]*]*+[A]*- composition. With A = TCNQ (7,7,8,8-tetracyano-p-quinodimethane) a 1:2 electron-transfer salt with FeCpCp forms. With A = TCNE (tetracyanoethylene) a pair of 1:1 salts as well as a pair of 2:3 salts of [FeCpCp]2[TCNE]3.S (S = CH2Cl2, THF) have been isolated and characterized by single-crystal X-ray diffraction. [FeCpCp][TCNE] consists of parallel 1-D.D(*+)A(*-)D(*+)A(*-)D(*+)A(*-). chains, while [FeCpCp][TCNE].MeCN has a herringbone array of D(*+)A2(2-)D(*+) dimers separated by solvent molecules. Although each [TCNE](-) is disordered, the diamagnetic [TCNE]2(2-) dimer is structurally different from those observed earlier with an intradimer separation of 2.79 A. The [TCNE](-) in the 2:3 [FeCpCp]2[TCNE]3.S exists as an eclipsed diamagnetic [TCNE]2(2-) dimer with an intradimer ethylene C.C separation of 2.833 and 2.903 A for the CH2Cl2- and THF-containing materials, respectively. The bond distances and angles for all the cations are essentially equivalent, and the distances are essentially equivalent to those previously reported for [FeCp2](*+) and [FeCp2](*+) cations. The average Fe-C5H5-ring and Fe-C5Me5-ring centroid distances are 1.71 and 1.69 A, respectively, which are 0.05 A longer than reported for Fe(II)CpCp. The one-electron reduction potential for Fe(II)CpCp is 0.11 V (vs SCE). The 5 K EPR of [FeCpCp](*+)[BF4](-) exhibits an axially symmetric powder pattern with g(parallel) = 4.36 and g(perpendicular) = 1.24, and the EPR parameters are essentially identical to those reported for ferrocenium and decamethylferrocenium. The high-temperature magnetic susceptibility for polycrystalline samples of these complexes can be fit by the Curie-Weiss law, chi = C/(T - theta), with low theta values and mu(eff) values from 2.08 to 3.43 mu(B), suggesting that the polycrystalline samples measured had varying degrees of orientation. [FeCpCp][TCNE] exhibits the highest effective moment of 3.43 mu(B)/Fe and weak ferromagnetic coupling, as evidenced from the theta of 3.3 K; however, unexpectedly, it does not magnetically order above 2 K. The formation of the four phases comprising FeCpCp and TCNE emphasizes the diversity of materials that may form and the present inability to predict neither solid-state compositions nor structure types.