Synthesis of (-)-ilimaquinone via a radical decarboxylation and quinone addition reaction

[reaction: see text] A stereoselective synthesis of (-)-ilimaquinone (4) is presented. The synthetic strategy is based on a novel radical decarboxylation and quinone addition methodology that produces quinone 7 from reaction of thiohydroxamic acid derivative 8 with benzoquinone (9). Final functionalization of 7 to ilimaquinone (4) is achieved by exploring the electronic effects of the residual thiopyridyl group.     

Simultaneous Determination of Enalapril and Enalaprilat in Human Plasma by LC-MS: Application to a Bioequivalence Study

A rapid, simple and specific liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method has been developed and validated for the simultaneous determination of enalapril and its major active metabolite enalaprilat in human plasma. Benazepril hydrochloride was used as the internal standard. Plasma was deproteinized with acetone and centrifuged. The supernatant was transferred and evaporated to dryness and the residue dissolved in mobile phase. Samples were separated on a C18 column with a mobile phase of methanol–20 mM ammonium acetate (53:47, v/v) containing 0.15% trifluoracetic acid (v/v) with a pH of 3.0. Enalapril, enalaprilat and the internal standard were measured by electrospray positive selective ion monitoring mode. The method was validated over a linear range of 1.56–400 ng mL⁻¹ and the limits of quantification were 1.56 ng mL⁻¹ for both enalapril and enalaprilat using 0.1 mL plasma. Extraction efficiency was more than 84% and recoveries were in range of 93.65–101.17%. The intra-day relative standard deviations (RSD) were less than 8.16 and 7.05% and inter-day RSDs were within 8.42 and 5.72% for enalapril and enalaprilat, respectively. The storage stability of QC samples was investigated under various conditions. The method was successfully applied for the evaluation of the pharmacokinetics and bioequivalence of enalapril and enalaprilat in 20 healthy volunteers after an oral dose of 20 mg enalapril maleate.     

De novo sequencing of tryptic peptides sulfonated by 4-sulfophenyl isothiocyanate for unambiguous protein identification using post-source decay matrix-assisted laser desorption/ionization mass spectrometry

A simple method of solid-phase derivatization and sequencing of tryptic peptides has been developed for rapid and unambiguous identification of spots on two-dimensional gels using post-source decay (PSD) matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The proteolytic digests of proteins are chemically modified by 4-sulfophenyl isothiocyanate. The derivatization reaction introduces a negative sulfonic acid group at the N-terminus of a peptide, which can increase the efficiency of PSD fragmentation and enable the selective detection of only a single series of fragment ions (y-ions). This chemically assisted method avoids the limitation of high background normally observed in MALDI-PSD spectra, and makes the spectra easier to interpret and facilitates de novo sequencing of internal fragment. The modification reaction is conducted in C(18) microZipTips to decrease the background and to enhance the signal/noise. Derivatization procedures were optimized for MALDI-PSD to increase the structural information and to obtain a complete peptide sequence even in critical cases. The MALDI-PSD mass spectra of two model peptides and their sulfonated derivatives are compared. For some proteins unambiguous identification could be achieved by MALDI-PSD sequencing of derivatized peptides obtained from in-gel digests of phosphorylase B and proteins of hepatic satellite cells (HSC).     

Synthesis and structural characterization of trivalent amino acid derived chiral phosphorus compounds

Reaction of the N-toluenesulfonyl derivatives of (S)-alanine, phenylalanine, and valine (4-6) with PhPCl(2) gave in high yield the 4-methyl, benzyl, and isopropyl derivatives (7-9) of 2-phenyl-1-p-toluenesulfonyl-1,3,2-oxazaphospholidin-5-one. The ratios of the (2S,4S)/(2R,4S) diastereomers (cis/trans isomers) were 1:1, 2:1, and 10:1 for the methyl, benzyl, and isopropyl derivatives 7a,b, 8a,b, and 9a,b, respectively. For 7a,b, both isomers could be crystallized, but for the others only the major isomers were isolable. The X-ray crystal structure of 9a shows that the isopropyl and phenyl groups are mutually cis and that the tolyl moiety is oriented s-trans to both the isopropyl and phenyl groups. Reaction of 6 with Cl(2)PCH(2)CH(2)PCl(2) (10) gave a 56:38:7 mixture of the cis/cis, cis/trans, and trans/trans diphosphorus heterocycles 11a-c. The major isomer could be crystallized and isolated free of the other diastereomers. Reaction of 6 with EtPCl(2) gave a 6:1 mixture of cis/trans isomers of the ethyl-substituted heterocycles 12a,b as an inseparable oil but allowed confirmation of the structure of 11a. Slow epimerization at phosphorus may occur by inversion but more likely by ring opening/closure, since 7b, 9a, and 11a give rise upon standing in solution to mixtures containing starting material and 7a, 9b, and 11b, respectively, along with the free amino acid derivatives 4 and 6. The NMR spectra, and in particular the coupling constants between the alpha-hydrogen atom of the amino acid moiety and phosphorus, were used to establish the identities of the cis and trans isomers. Reaction of 9a with (THF)W(CO)(5) gave the phosphorus-ligated adduct (9a)W(CO)(5) (13), and the IR spectrum of this complex shows that 9a is a strongly electron-withdrawing ligand. The geometry of the sulfonamide moiety is discussed in detail, as are the (1)H NMR coupling constants. The data are consistent with the presence of little steric interaction between the cis isopropyl and phosphorus substituent in 9a, 11a, and 12a and orientation of the tolyl moiety s-cis to the isopropyl group in 9b, 12b, and 13.     

野生与种植青海川西獐牙菜中微量元素的测定

为了对比野生与种植青海川西獐牙菜中微量元素的变化,分别采集野生川西獐牙菜与种植青海川西獐牙菜种子采收前后的全植株,采用原子吸收光谱仪测定了其铜、锌、铁、锰、钴等微量元素含量。结果表明,野生川西獐牙菜较种植青海川西獐牙菜中微量元素含量高,种植川西獐牙菜在成熟种子采收后较采收前(花果期)铁、锰、钴、锌等元素含量高。     

Synthesis of 2‐Dihydrooxadiazolinyl Chromones

Reactions of the substituted 2‐formyl chromones with aroylhydrazines gave corresponding 2‐(aroylhydrazonomethylidyne) chromones. Then 2‐(3′‐acetyl‐5′‐aryl‐2′,3′‐dihydro‐1′,3′,4′‐oxadiazol‐2′‐yl) chromones were prepared by these 2‐(aroylhydrazonomethylidyne) chromones under refluxing with Ac₂O. All target compounds were characterized through elemental analysis and IR, ¹H NMR, MS.     

5-芳酰氨基-2-苯基-2H-1, 2, 4-噻二唑-3-酮的合成

用1-芳酰基-5-苯基-2-硫代双脲与溴进行氧化成环反应制备了九个新的5-芳酰氨基-2-苯基-2H-1, 2, 4-噻二唑-3-酮, 相应的1-芳酰基-5-苯基-2-硫代双脲可以通过苯基脲与酰基异硫氰酸酯加成制得。     

Preparation of a highly active nanocrystalline TiO2 photocatalyst from titanium oxo cluster precursor

Nanocrystalline TiO₂ (sample S1) was prepared from a titanium oxo cluster (Ti₇O₄(OEt)₂₀) precursor via a sol-gel route. This photocatalyst showed a higher photocatalytic activity than the TiO₂ (sample S2) obtained from titanium tetraisopropoxide. The samples were characterized by thermal analysis (TGA/DSC), X-ray diffraction, micro-Raman spectroscopy, transmission electron microscopy, N₂ adsorption (BET surface area), infrared absorption spectroscopy (FT-IR) and X-ray photoelectron spectroscopy. The characterization results show that both samples are anatase nanocrystals with particle sizes of about 12 nm, but the more photocatalytically active sample S1 has more surface hydroxyl groups and larger surface area and pore volume than sample S2.     

Solid-phase Synthesis of-Haloaldehydes from Polymer-supported 4-(Phenylseleno)morpholine

Polymer-supported reagents for organic synthesis are enjoying a renewed popularity with the emergence of combinatorial chemistry in recent years1. 4-(Arylseleno)morpholines formed in situ are useful -seleno-introducing reagents for saturated aldehydes2. -Sele- noaldehydes, as a frequently used intermediates, can be converted into -haloaldehydes by halogenating reaction3. However, organic selenium reagents always have a foul smell and are quite toxic, which is often problematic in organic sy…     

Synthesis of （2R,4R）—2—N—tert—Butyloxycarbonyl Amino—4,5—epoxido—valeric Acid Methyl Ester

The stereoselective synthesis of (2R,4R)-2-N-tert-butyloxycarbonyl amino-4,5-epoxido-valeric acid methyl ester 8,which is the key intermediate for the synthesis of (2′S,2R)-3-trans-nitrocyclopropyl-alanine,was first accomplished.