Diversity of complexes based on p-nitrobenzoylhydrazide, benzoylformic acid and diorganotin halides or oxides self-assemble: Cytotoxicity, the induction of apoptosis in cancer cells and DNA-binding properties.

Eight organotin(IV) complexes (C1-C8) have been synthesized and characterized by elemental analysis, fourier transform infrared spectroscopy (FT-IR), multinuclear nuclear magnetic resonance (1H, 13C and 119Sn NMR), high resolution mass spectroscopy (HRMS) and single crystal X-ray structural analysis. Crystallographic data show that C1 was a tetranuclear 16-membered macrocycle complex, C2-C4 and C7 were centrosymmetric dimer distannoxane and there was a Sn2O2 four-membered ring in the middle of the molecule, respectively, C5 and C6 are monoorganotin complexes due to the dehydroalkylation effect during the reaction, while C8 forms a one-dimensional chain structure. The cytotoxicity of all complexes were tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays against three human tumor cell lines NCI-H460, MCF-7 and HepG2. The dibutyltin complex C2 has been shown to be more potent antitumor agents than other complexes and carboplatin. Cell apoptosis study of C2 with the high activity on HepG2 and MCF-7 cancer cell lines was investigated by flow cytometry, it was shown that the antitumor activity of C2 was related to apoptosis, but it has different cell cycle arrest characteristics from platinum compounds, and the proliferation was inhibited by blocking cells in S phase. The DNA binding activity of the C2 was studied by UV-visible absorption spectrometry, fluorescence competitive, viscosity measurements and gel electrophoresis, results shown C2 can be well embedded in the double helix of DNA and cleave DNA.

Desilylative activation of TMSCN in chemoselective Strecker-Ugi type reaction: functional fused imidazoles as building blocks as an entry route to annulated purines.

A pathway of desilylative activation of TMSCN as a functional isonitrile equivalent, and DABCO-THF as an appropriate system for activation in a chemoselective Strecker-Ugi type reaction, has rendered ethyl glyoxalate and various heterocyclic-2-amidines as feasible substrates, and afforded the successful synthesis of 3-amino-2-carboxyethyl substituted fused imidazoles as useful building blocks. This class of functional scaffold has provided, via construction of the fused pyrimidinone motif, the synthesis of biologically important C8-N9 annulated purines, adenines and their oxo/thio analogs. This new approach is convenient and flexible for the preparation of versatile purine-condensed heterocycles.

Silver-catalyzed amidation of benzoylformic acids with tertiary amines via selective carbon-nitrogen bond cleavage.

A novel approach towards the synthesis of α-ketoamides using tertiary amines as nitrogen group sources via C-N bond cleavage has been developed. In the presence of Ag2CO3 and K2S2O8, α-keto acids reacted with tertiary amines to afford the corresponding α-ketoamides in good yields.

α-Oxo aldehyde or glyoxylyl group chemistry in peptide bioconjugation.

Since the 1990s, α-oxo aldehyde or glyoxylic acid chemistry has inspired a vast array of synthetic tools for tailoring peptide or protein structures, for developing peptides endowed with novel physicochemical properties or biological functions, for assembling a large diversity of bioconjugates or hybrid materials, or for designing peptide-based micro or nanosystems. This past decade, important developments have enriched the α-oxo aldehyde synthetic tool box in peptide bioconjugation chemistry and explored novel applications. The aim of this review is to give a large overview of this creative field.

Pd-catalyzed tandem cyclization of ethyl glyoxalate and amines: rapid assembly of highly substituted cyclic dehydro-α-amino acid derivatives.

A novel cascade cyclization of ethyl glyoxalate and amines proceeds in the presence of Pd(TFA)(2) (5 mol %) to give the cyclic dehydro-α-amino acid derivatives. This method provides a fast and simple access to highly substituted dihydro-pyrrol-2-ones in good yields.

Three-component glycolate Michael reactions of enolates, silyl glyoxylates, and α,ß-enones.

Silyl glyoxylates react with enolates and enones to afford either glycolate aldol or Michael adducts. Product identity is controlled by the countercation associated with the enolate. Reformatsky nucleophiles in the presence of additional Zn(OTf)(2) result in aldol coupling (A), while lithium enolates provide the Michael coupling (B). Deprotonation of the aldol product A with LDA induces equilibration to form the minor diastereomer of Michael product B. This observation suggests that formation of the major diastereomer of Michael product B does not occur via an aldol/retro-aldol/Michael sequence.

Asymmetric addition of arylboronic acids to glyoxylate catalyzed by a ruthenium/Me-BIPAM complex.

The enantioselective synthesis of α-hydroxy esters by ruthenium-catalyzed 1,2-addition of arylboronic acids to tert-butyl glyoxylate is described. The use of RuCl(2)(PPh(3))(3) with (R,R)-Me-BIPAM gave optically active mandelic acids of up to 99% ee. Addition of a fluoride salt such as potassium fluoride (KF) or caesium fluoride (CsF) was effective for achieving high enantioselectivities.

Exploratory experiments on the chemistry of the "glyoxylate scenario": formation of ketosugars from dihydroxyfumarate.

In the context of a "glyoxylate scenario" of primordial metabolism, the reactions of dihydroxyfumarate (DHF) with reactive small molecule aldehydes (e.g., glyoxylate, formaldehyde, glycolaldehyde, and glyceraldehyde) in water were investigated and shown to form dihydroxyacetone, tetrulose, and the two pentuloses, with almost quantitative conversion. The practically clean and selective formation of ketoses in these reactions, with no detectable admixture of aldoses, stands in stark contrast to the formose reaction, where a complex mixture of linear and branched aldoses and ketoses are produced. These results suggest that the reaction of DHF with aldehydes could constitute a reasonable pathway for the formation of carbohydrates and allow for alternative potential prebiotic scenarios to the formose reaction to be considered.

Indium-mediated allylation and Reformatsky reaction on glyoxylic oximes under ultrasound irradiation.

A novel and more convenient method for the indium-promoted allylation of glyoxylic oximes based on the use of ultrasonic waves is reported. A similar procedure was used to develop the first example reported in the literature of an indium-mediated Reformatsky reaction on oxime ethers.

Polymeric ethyl glyoxylate in an asymmetric aldol reaction catalyzed by diarylprolinol.

Diarylprolinol was found to be an effective organocatalyst of the direct, enantioselective aldol reaction of commercially available polymeric ethyl glyoxylate, affording gamma-ethoxycarbonyl-beta-hydroxy aldehydes, versatile synthetic intermediates, in good yield with excellent enantioselectivity.

Highly diastereoselective synthesis of modified nucleosides via an asymmetric multicomponent reaction.

We have developed a practical synthesis of unique nucleoside derivatives via TiCl(4) promoted multicomponent reaction of optically active dihydrofuran, ethyl pyruvate/glyoxylate, and a TMS protected nucleobase in a single-pot operation.

Novel N-substituted indol-3-ylglyoxylamides probing the LDi and L1/L2 lipophilic regions of the benzodiazepine receptor site in search for subtype-selective ligands.

Novel N-substituted indol-3-ylglyoxylamides (10-37) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR). In an effort to achieve affinity-based selectivity among BzR subtypes, these compounds were designed to probe the LDi and L2 lipophilic regions. Taking the alpha1-selective benzylindolylglyoxylamides Ia and Ib as leads, we varied the substituent on the benzylamide phenyl ring (compounds 10-23) or replaced the benzyl moiety with alkyl groups (compounds 24-37). The above structural changes gave no shift of selectivity from the alpha1 toward the alpha2 or alpha5 subtypes, thus confirming that a ligand which occupies the LDi region probably exhibits alpha1 selectivity, despite its interactions with other lipophilic areas in the receptor binding cleft. Compound 11 (N-(p-methylbenzyl)-5-nitroindol-3-ylglyoxylamide), which selectively binds with a full agonist efficacy at the alpha1 receptor subtype and displays sedative action, can be regarded as an interesting potential zolpidem-like sedative-hypnotic agent.

New solid support for the synthesis of 3'-oligonucleotide conjugates through glyoxylic oxime bond formation.

A novel solid support 1 was synthesized to incorporate glyoxylic aldehyde functionality at the oligonucleotide 3'-terminus. 6-mer and 11-mer oligonucleotide sequences containing 3'-glyoxylic aldehyde functionality were prepared by using this support. These modified oligonucleotides were coupled to reporters containing an aminooxy group to prepare oligonucleotide 3'-conjugates through glyoxylic oxime bond formation. The hydrolytic stability of a glyoxylic oxime linkage was also investigated. [reaction: see text].

A new method of ion chromatography technology for speedy determination and analysis in organic electrosynthesis of glyoxylic acid.

Based on ion chromatography (IC) technology, we have developed a new method that combines ion chromatography with a conductivity detector to separate and determine the substances of glyoxal, glycolic acid, oxalic acid and glyoxylic acid. The ion chromatography was applied for the first time in quantitative determination of substances involved in electrosynthesis of glyoxylic acid. The method has been applied to separate and analyze simultaneously either glyoxylic acid and glyoxal in electroxidation of glyoxal, or glyoxylic acid and oxalic acid in electroreduction of oxalic acid. An aqueous Na2CO3-NaHCO3 or NaOH-Na2CO3 solution was confirmed to be the most desirable eluent. The experimental results demonstrated that the detection sensitivity is ahead of ppm grade, and the variation coefficients such as the retention time, the peak height and the peak area outperform 2%. All the recoveries of the detected substances are ranged between 97 and 103%. The method exhibits advantages of high selectivity, high sensitivity, speediness and simple apparatus requirement. Furthermore, simultaneous determination of a mixture of several substances can be achieved by the developed method, and even a neutral molecule of glyoxal can be also determined by choosing an appropriate composition and concentration of eluent.

New method to prepare peptide-oligonucleotide conjugates through glyoxylic oxime formation.

A new method to prepare peptide-oligonucleotide conjugates through chemoselective glyoxylic oxime linkage is reported. A novel phosphoramidite reagent, readily accessible from serine, was prepared and used in automated DNA synthesis to prepare oligonucleotides carrying a glyoxylic aldehyde functionality at the 5' terminus. This was efficiently coupled to a peptide functionalized with an aminooxy group. The method could be of general use to prepare a broad range of oligonucleotide conjugates.

Design, synthesis and antimalarial activity of a glyoxylylhydrazone library.

Synthesis of a new family of quinolylhydrazone derivatives and evaluation of their activity against a chloroquine-resistant strain of Plasmodium falciparum are described. The best compound displayed an activity 6-fold higher than chloroquine. None of the active compounds were found to inhibit beta-hematin formation in vitro in the same range as chloroquine and five among them displayed lower calculated vacuolar accumulation ratios, suggesting the implication of a different mechanism of action.

Addition of electrophilic and heterocyclic carbon-centered radicals to glyoxylic oxime ethers.

[reaction: see text] Stabilized primary radicals can be formed from alkyl halides in an atom transfer process with Et(3)B. This process depends on the strength of the carbon-halogen bond and the stability of the resulting primary radical. Radicals formed from benzyl iodide and ethyl iodoacetate add to glyoxylic oxime ethers; however, more electrophilic radicals do not. Glyoxylic oxime ethers are also good radical acceptors for heterocyclic carbon-centered secondary radicals, giving novel alpha-amino acid derivatives.

N,N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodiazepine receptor.

We report the synthesis and the affinity data at both the peripheral (PBR) and the central benzodiazepine receptors of a series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamide derivatives III, designed as conformationally constrained analogues of 2-phenylindole-3-acetamides II such as FGIN-1-27. Most of the new compounds showed a high specificity and affinity for PBR, with K(i) in the nanomolar to subnanomolar range. The most potent ligands (4-7, 9, 13-27) stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to or higher than that of classical ligands. The SARs of this new class of compounds are discussed.

Regioselectivity in palladium-indium iodide-mediated allylation reaction of glyoxylic oxime ether and N-sulfonylimine.

Allylation reaction of electron-deficient imines with allylic alcohol derivatives in the presence of a catalytic amount of palladium(0) complex and indium(I) iodide was studied. The reversibility of allylation was observed in the reaction of glyoxylic oxime ether having camphorsultam. As the important effect of water on regioselectivity, the gamma-adducts were kinetically formed from monosubstituted allylic reagents in the presence of water. The selective formation of thermodynamically stable alpha-adducts was observed in anhydrous THF. In contrast, the allylation of N-sulfonylimine gave the gamma-adducts with high regioselectivities even under anhydrous reaction conditions.