Polymer-supported thioanisole: a versatile platform for organic synthesis reagents

A new cross-linked polystyrene-supported thioanisole reagent is reported. This reagent incorporates the flexible JandaJel™ cross-linker and can be treated with methyl trifluoromethanesulfonate to form the corresponding sulfonium salt. This salt can in turn be deprotonated to form a polymer-supported sulfur ylide that is able to react with aldehydes and ketones to form epoxides. The thioanisole reagent can also be oxidized to form an insoluble sulfoxide reagent that is useful in Swern oxidation reactions. In these reactions, the polymer-supported thioanisole-based reagents can be recovered, regenerated and reused.     

Regioselective synthesis of 1,3,5- and 1,3,4,5-substituted pyrazoles via acylation of N-Boc-N-substituted hydrazones

Acylation of N-Boc-N-methylhydrazones followed by TFA treatment affords regioselective access to substituted pyrazoles. Both regioisomers of 1-methyl-3,5-disubstituted-1H-pyrazoles can be selectively obtained. This procedure can also be employed for the regioselective preparation of fully substituted 1H-pyrazoles.     

An efficient synthesis of ortho-N-Boc-arylmethyl ketone derivatives

A new and efficient method for the preparation of ortho-N-Boc-arylmethyl ketone derivatives is reported. The reaction involves the intermediacy of a 4-methylene-3,1-benzoaxin-2-one moiety which smoothly converts to the target compounds under acidic conditions. The ortho-N-Boc-arylmethyl ketone derivatives can be formed in a one-pot reaction or alternatively the 4-methylene-3,1-benzoaxin-2-ones can be isolated and subsequently transformed into the desired products.     

The separation and determination of nitrophenol isomers by high-performance capillary zone electrophoresis

o-Nitrophenol, m-nitrophenol, and p-nitrophenol could well be separated by capillary zone electrophoresis (CZE) by only adjusting the run buffer with methanol. Efficiency up to 10⁵ theoretical plates per meter was achieved. The effects of several important factors were investigated to find optimum conditions. The linear range, regression equation, and the recovery were given. This method possessed the advantages of simplicity, rapidity, and good reproducibility; it can be developed for the separation of practical samples in environment analysis.     

Synthesis of granulatimide bis-imide analogues

The synthesis of dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones, structurally related to granulatimide is reported. These compounds can be considered as granulatimide analogues in which a maleimide heterocycle replaces the imidazole moiety. The synthesis of pyridino[2,3-b]dipyrrolo[3,4-e:3,4-g]indole-1,3,4,6-tetraones is also reported. In these compounds, a 7-azaindole unit replaces the indole moiety present in the granulatimide and isogranulatimide structures.     

Electrochemical oxidation of catechols in the presence of ketene N,O-acetals: indole formation versus α-arylation

Anodic oxidation of catechols has been investigated in the presence of ketene N,O-acetals using cyclic voltammetry and constant current electrolysis methods. The results show that in the presence of ketene N,O-acetals, the anodic oxidation of 4-methylcatechol affords α-arylated products in satisfactory yields. Meanwhile, indoles can be synthesized from simple 3-substituted catechols or catechol itself following an ECEC mechanism. In addition, either α-arylation or indole formation could be the dominant pathway by simply modifying the composition of the electrolyte solution.     

Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of dipyrrolo[3,4-a:3,4-c]carbazole-triones

The syntheses of dipyrrolo[3,4-a:3,4-c]carbazole-1,4,6-triones and dipyrrolo[3,4-a:3,4-c]carbazole-3,4,6-triones are reported. These compounds can be considered as granulatimide analogues in which a maleimide replaces the imidazole moiety and a five-membered lactam ring replaces the upper maleimide. The Chk1 inhibitory properties of the more soluble compounds have been evaluated and their in vitro antiproliferative activities toward three tumor cell lines: murine leukemia L1210, and human colon carcinoma HT29 and HCT116. Due to their insolubility, the biological activities of the other compounds in this series could not be evaluated. All the tested compounds proved to be potent Chk1 inhibitors.     

Pd-NHC-catalyzed synthesis of diaryl ketones

With N-hetereocyclic carbene and palladium catalysis, diaryl ketones with a variety of functional groups that span from electron withdrawing to electron donating substitutions can be conveniently synthesized using the corresponding aryl boronic acid and N-acyloxyphthalimide.     

Construction of pyrazolo[3,4-b]pyridines and pyrazolo[4,3-c]pyridines by ring closure of 3-acylpyridine N-oxide tosylhydrazones

3-Acylpyridine N-oxide tosylhydrazones give good overall yields of a mixture of pyrazolo[3,4-b]pyridines and pyrazolo[4,3-c]pyridines when treated with an electrophilic additive and an amine base. (Z)-Hydrazones cyclize readily, while (E)-hydrazones fail to react under the reported conditions. The reaction takes place at room temperature, and moderate regiocontrol over the cyclization can be achieved by varying the electrophile/solvent combination.     

Covalent selection of the thiol proteome on activated thiol sepharose: A robust tool for redox proteomics

Protein thiols contribute significantly to antioxidant defence and selective oxidation of cysteines is important in signal transduction even in sub-stress scenarios. However, cysteine is the second rarest residue in proteins and it can be difficult to target low-abundance thiol (-SH)-containing proteins in proteomic separations. Activated thiol sepharose (ATS) allows covalent selection of -SH-containing proteins which can then be recovered by reduction with mercaptoethanol or dithiothreitol. This is a robust method for enriching -SH-containing proteins. We have used ATS to estimate the percentage (by weight) of thiol-containing proteins in cell extracts from a range of biological sources: a bacterium, Escherichia coli; a fungus, Trichoderma harzianum; and a bivalve mollusc Mytilus edulis. -SH-containing proteins account for 2.52% (E. coli), 1.4% (T. harzianum) and 1.4% (M. edulis) of total protein. Exposure to pro-oxidants did not materially alter these values. On removal of low M_r thiols such as glutathione, the values for M. edulis did not significantly change but those for T. harzianum increased threefold. The two-dimensional electrophoresis profiles of ATS-selected proteins for each organism were compared in control and pro-oxidant-exposed preparations. This revealed that some proteins present in controls were absent in pro-oxidant-treated extracts which we attribute to thiol oxidation. ATS has significant potential in enrichment for -SH-containing proteins in redox proteomics.     

N,N,N,N-Tetramethyl-1,3-propanediamine as the catalyst of choice for the Baylis-Hillman reaction of cycloalkenone: rate acceleration by stabilizing the zwitterionic intermediate via the ion-dipole interaction

N,N,N^′,N^′-Tetramethyl-1,3-propanediamine (TMPDA) can be used as an efficient catalyst for the Baylis-Hillman reaction of cycloalkenones. The increased reaction rate was thought be derived from the stabilizing effect of the zwitterionic intermediate via the ion-dipole interaction.     

Grignard reagent-promoted 6-endo-dig cyclization: instantaneous synthesis of original dipyrido[1,2-a:3′,4′-d]imidazole

Dipyrido[1,2-a:3′,4′-d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2-a]pyridines via an efficient Grignard reagent-promoted 6-endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cyanoimidazo[1,2-a]pyridine was necessary as this coupling reaction is known to be largely influenced by the nature of the 2-substituent.     

Iron fluoride: the most efficient catalyst for one-pot synthesis of 4H-pyrimido[2,1-b]benzothiazoles under solvent-free conditions

A new iron fluoride assisted convenient and efficient strategy for the preparation of 4H-pyrimido[2,1-b]benzothiazoles derivatives in solvent-free media is described. The reactions can be performed at low-catalyst loadings with excellent functional group tolerance. The catalyst can be readily recovered and reused for next reaction for at least three runs without any significant impact on the yields of the products. The easy recovery of the catalyst and high yield of the products make the protocol attractive, sustainable, and economic.     

Rapid stereoselective access to the tetracyclic core of puupehenone and related sponge metabolites using metal-free radical cyclisations of cyclohexenyl-substituted 3-bromochroman-4-ones

The tetracyclic nucleus of puupehenone, 15-oxopuupehenol and other sesquiterpene-phenol natural products can be assembled stereoselectively in three steps, the last of these being the 6-endo-trig cyclisation of an alpha-keto radical generated from a substituted 2-(2-cyclohexenyl)ethyl 3-bromo-4-chromanone under metal-free conditions.     

Analysis of ultratrace triorganotin compounds in aquatic organisms by using capillary electrophoresis-inductively coupled plasma mass spectrometry

A microwave-assisted extraction used to extract trace triorganotin from aquatic organisms and a sensitive analytical method for the determination of ultratrace triorganotin (namely trimethyltin, triethyltin, tripropyltin and tributyltin) with capillary electrophoresis-inductively coupled plasma mass spectrometry were firstly described in this study. The extraction method is simple, effective and can be used to extract trace triorganotin in aquatic organisms within several min. The analytical method has a much lower detection limit of 0.2-0.7 ng Sn/mL for triorganotin compounds, and can be used to determine trace triorganotin in aquatic organisms directly without any derivatization and preconcentration. Using above methods, we have successfully determined trimethyltin, triethyltin, tripropyltin and tributyltin in dried Mya arenaria Linnaeus and Corbicula fluminea within 17 min with a recovery of 93-104% and a RSD (relative standard deviation, n = 6) of 2-5%. Our results showed that dried M. arenaria Linnaeus contained an extremely high tributyltin of 5.1 μg Sn/g dried weight, indicating that it may be a good biomarker for the organotin pollution in ocean.     

Hydrogen cycling induced diffraction peak broadening in C14 and C15 Laves phases

The diffraction peak broadening induced by hydrogen absorption-desorption cycling has been analyzed in four different Laves phase compounds with the C14 and C15 structures. The broadening is due to strain most probably originating from dislocations generated at the interface between the α and β hydride phases in connection with the cell volume difference between the two phases. It has been shown that it is strongly compound dependent. In the case of the C14 structure, the broadening is large and isotropic, and the latter can be related to the isotropy of the elastic constants of the metallic phase. The broadening is less for the compounds with the C15 structure, which can be related to a possibly softer lattice. Better ageing properties after long-term cycling are predicted for this crystal structure.     

Functionalization of aminocrown ethers with [2H]-chromene units by Buchwald-Hartwig C-N coupling for constructing of photoswitchable molecular devices

Functionalization of the diaminodibenzocrown ethers with 2H-[1]benzopyrane and 3H-naphtho[2,1-b]pyrane units by Buchwald-Hartwig C-N coupling was developed. It is demonstrated that the novel molecule possesses photochromic properties that can be modified by the complex formation process.     

Biocatalytic preparation of enantioenriched 3,4-dihydroxypiperidines and theoretical study of Candida antarctica lipase B enantioselectivity

Enzymatic acetylations of N-substituted cis- and trans-3,4-dihydroxypiperidine and hydrolysis of their diacetylated derivatives have been studied. High enantioselectivities are obtained with Pseudomonas cepacia lipase and Candida antarctica lipase B for the hydrolysis of the trans-derivative, while the cis-derivatives are not adequate substrates in the same biocatalytic conditions. The enantiopreference of these processes can be rationalized by means of a molecular modelling study.     

The preparation and some chemistry of 2,2-dimethyl-1,2-dihydroquinolines

The cyclisation of N-(1,1-dimethylpropargyl) anilines, using cuprous chloride in refluxing toluene, yields 6-substituted-2,2-dimethyl-1,2-dihydroquinolines. The reactivity of the double bond in the heterocyclic ring of these products is exemplified by chlorination, to yield 6-substituted-3,4-cis-dichloro-2,2-dimethyl-1,2,3,4-tetrahydroquinolines which can be selectively dechlorinated to provide 6-substituted-3-chloro-2,2-dimethyl-1,2,3,4-tetrahydroquinolines; epoxidation to yield an epoxide, which can be hydrogenolysed to the corresponding 3-hydroxy product and in turn oxidised to the 3-keto derivative; and oxymercuration to provide a 4-hydroxy product and hence a 4-keto derivative. Dehydrochlorination of a 3,4-dichloro product provides a 3-chloro-1,2-dihydroquinoline which can be hydrolysed to a 3-keto system. The formation of cis 3,4-dichloro products from the chlorination, as well as the formation of a cis chlorohydrin from the chlorination of N-acetyl-2,2,6-trimethyl-1,2-dihydroquinoline in partially aqueous solution, suggests that N-acetyl, or N-trifluoroacetyl groups, participate in the addition process.     

The biocatalytic conversion of 8-hydroxymanzamine A to manzamine A

The selective dehydroxylation of 8-hydroxymanzamine A (1) to form manzamine A (2) can be completed by fermentation with Fusarium solani or Streptomyces seokies. This unique biocatalytic conversion is important due to the fact that manzamine A has more desirable biological activity when assayed in a murine model against malaria.