Synthesis of Chiral Tertiary Boronic Esters: Phosphonate-Directed Catalytic Asymmetric Hydroboration of Trisubstituted Alkenes.

Highly enantioselective rhodium-catalyzed hydroboration of allylic phosphonates by pinacolborane affords chiral tertiary boronic esters. The ß-borylated phosphonates are readily converted to chiral ß- and γ-hydroxyphosphonates and aminophosphonates and to phosphonates bearing a quaternary carbon stereocenter. The utility of the latter is illustrated by the synthesis of (S)-(+)-bakuchiol methyl ether.

Self-healing pH-sensitive poly[(methyl vinyl ether)-alt-(maleic acid)]-based supramolecular hydrogels formed by inclusion complexation between cyclodextrin and adamantane.

Self-healing materials are of interest for drug delivery, cell and gene therapy, tissue engineering, and other biomedical applications. In this work, on the base of biocompatible polymer poly(methyl vinyl ether-alt-maleic acid) (P(MVE-alt-MA)), host polymer ß-cyclodextrin-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-ß-CD) and guest polymer adamantane-grafted P(MVE-alt-MA) (P(MVE-alt-MA)-g-Ad) were first prepared. Then through taking advantage of the traditional host-guest interaction of ß-cyclodextrin and adamantane, a novel self-healing pH-sensitive physical P(MVE-alt-MA)-g-ß-CD/P(MVE-alt-MA)-g-Ad supramolecular hydrogels were obtained after simply mixing the aqueous solution of host polymer and guest polymer. This kind of supramolecular hydrogels not only possess pH-sensitivity, but also possess the ability to repair themselves after being damaged.

Acylated Glycosidic Acid Methyl Esters Generated from the Convolvulin Fraction of Rhizoma Jalapae Braziliensis by Treatment with Indium(III) Chloride in Methanol.

Four hexaglycosides of methyl 3S,12S-dihydroxyhexadecanoate (1-4) were provided after treatment of the crude convolvulin fraction from Rhizoma Jalapae Braziliensis (the root of Ipomoea operculata (GOMES) MART., Convolvulaceae) with indium(III) chloride in methanol. The structures of 1-4 were elucidated on the basis of spectroscopic and chemical methods. Their sugar moieties were partially acylated with organic acids including (3S,9R)-3,6:6,9-diepoxydecanoic (exogonic) acid, (E)-2-methylbut-2-enoic (tiglic) acid, and isovaleric acid.

Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono- and Dimethyl Ethers.

The study of chemistry of naturally occurring compounds and the synthesis of their derivatives is fundamentally important for the development of new drugs. In this work, dehydrodieugenol (DHDE) was obtained through oxidative coupling of eugenol, promoted by an aqueous mixture of potassium ferricyanide (K3 [Fe(CN)6 ]) and NH3  · H2 O. The partial methoxylation of DHDE with MeI and K2 CO3 mainly resulted in the molecular-shaped monomethyl ether (DHDE-1MeO) and its dimethyl ether derivative (DHDE-2MeO). The products from the reactions were characterized by (1) H- and (13) C-NMR spectroscopy. Additionally, these studies have reported the antileishmanial activity of DHDE against Leishmania amazonensis (IC50 value of 42.20 µg ml(-1) ) and shown that partial methoxylation of DHDE results in a significant increase in its antiparasitic activity (IC50 value of 13.68 µg ml(-1) ). Based on in vitro bioassays, DHDE-1MeO has shown the highest leishmanicidal activity in promastigota form. Production by direct one-step synthesis of this monomethoxylated compound can be considered to be a cost-effective and environmentally friendly method with a short reaction time.

Synthesis of Chiral, Enantiopure Allylic Amines by the Julia Olefination of α-Amino Esters.

The four-step conversion of a series of N-Boc-protected l-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral ß-ketosulfones, and the reductive elimination of related α-acetoxysulfones. The overall transformation takes place under mild conditions, with good yields, and without loss of stereochemical integrity, being in this respect superior to the conventional Julia reaction of α-amino aldehydes.

Micro-total envelope system with silicon nanowire separator for safe carcinogenic chemistry.

Exploration and expansion of the chemistries involving toxic or carcinogenic reagents are severely limited by the health hazards their presence poses. Here, we present a micro-total envelope system (µ-TES) and an automated total process for the generation of the carcinogenic reagent, its purification and its utilization for a desired synthesis that is totally enveloped from being exposed to the carcinogen. A unique microseparator is developed on the basis of SiNWs structure to replace the usual exposure-prone distillation in separating the generated reagent. Chloromethyl methyl ether chemistry is explored as a carcinogenic model in demonstrating the efficiency of the µ-TES that is fully automated so that feeding the ingredients for the generation is all it takes to produce the desired product. Syntheses taking days can be accomplished safely in minutes with excellent yields, which bodes well for elevating the carcinogenic chemistry to new unexplored dimensions.

Activation of Marginally Reactive Boron Enolates by MeLi for the Formation of Enol Phosphates and Synthesis of the Δ(9)-THC Intermediate.

The addition of MeLi to boron enolates produced by the 1,4-addition of Ar2Cu(CN)Li2 to BF3·OEt2-activated enones was followed by the reaction with ClP(O)(OEt)2 to afford the corresponding enol phosphates in moderate to good yields. The scope of this method was examined with sterically hindered or electronically biased enones and/or reagents. This activation of boron enolates was successfully applied to the synthesis of the methyl ether of Δ(9)-tetrahydrocannabinol.

Synthesis and degranulation-inhibiting activities of the proposed apteniols B, C, and G.

The synthesis of compounds with the structures proposed for the oxyneolignan apteniols B, C, and G is described. The diphenyl ether skeletons of the proposed apteniols were formed via Ullmann ether synthesis. In particular, the spectral data for the synthesized apteniols B, C, and G did not agree with those previously reported for the isolated compounds. Furthermore, the synthesized proposed apteniol B did not show degranulation-inhibiting activity, while the prepared proposed apteniols C and G exhibited activities considerably weaker than that of the methyl ester of proposed apteniol A.

Low-energy electron-induced chemistry of condensed methanol: implications for the interstellar synthesis of prebiotic molecules.

In the interstellar medium, UV photolysis of condensed methanol (CH3OH), contained in ice mantles surrounding dust grains, is thought to be the mechanism that drives the formation of "complex" molecules, such as methyl formate (HCOOCH3), dimethyl ether (CH3OCH3), acetic acid (CH3COOH), and glycolaldehyde (HOCH2CHO). The source of this reaction-initiating UV light is assumed to be local because externally sourced UV radiation cannot penetrate the ice-containing dark, dense molecular clouds. Specifically, exceedingly penetrative high-energy cosmic rays generate secondary electrons within the clouds through molecular ionizations. Hydrogen molecules, present within these dense molecular clouds, are excited in collisions with these secondary electrons. It is the UV light, emitted by these electronically excited hydrogen molecules, that is generally thought to photoprocess interstellar icy grain mantles to generate "complex" molecules. In addition to producing UV light, the large numbers of low-energy (< 20 eV) secondary electrons, produced by cosmic rays, can also directly initiate radiolysis reactions in the condensed phase. The goal of our studies is to understand the low-energy, electron-induced processes that occur when high-energy cosmic rays interact with interstellar ices, in which methanol, a precursor of several prebiotic species, is the most abundant organic species. Using post-irradiation temperature-programmed desorption, we have investigated the radiolysis initiated by low-energy (7 eV and 20 eV) electrons in condensed methanol at - 85 K under ultrahigh vacuum (5 x 10(-10) Torr) conditions. We have identified eleven electron-induced methanol radiolysis products, which include many that have been previously identified as being formed by methanol UV photolysis in the interstellar medium. These experimental results suggest that low-energy, electron-induced condensed phase reactions may contribute to the interstellar synthesis of "complex" molecules previously thought to form exclusively via UV photons.

Synthesis and effects on cell viability of flavonols and 3-methyl ether derivatives on human leukemia cells.

Flavonoids are polyphenolic compounds which display an array of biological activities and are considered potential antitumor agents. Here we evaluated the antiproliferative activity of selected synthetic flavonoids against human leukemia cell lines. We found that 4'-bromoflavonol (flavonol 3) was the most potent. This compound inhibited proliferation in a concentration-dependent manner, induced apoptosis and blocked cell cycle progression at the S phase. Cell death was found to be associated with the cleavage and activation of multiple caspases, the activation of the mitogen-activated protein kinase pathway and the up-regulation of two death receptors (death receptor 4 and death receptor 5) for tumor necrosis factor-related apoptosis-inducing ligand. Moreover, combined treatments using 4'-bromoflavonol and TRAIL led to an increased cytotoxicity compared to single treatments. These results provide a basis for further exploring the potential applications of this combination for the treatment of cancer.

One-pot protection-glycosylation reactions for synthesis of lipid†II analogues.

(2,6-Dichloro-4-methoxyphenyl)(2,4-dichlorophenyl)methyl trichloroacetimidate (3) and its polymer-supported reagent 4 can be successfully applied to a one-pot protection-glycosylation reaction to form the disaccharide derivative 7 d for the synthesis of lipid II analogues. The temporary protecting group or linker at the C-6 position and N-Troc protecting group of 7 d can be cleaved simultaneously through a reductive condition. Overall yields of syntheses of lipid II (1) and neryl-lipid II N(ε)-dansylthiourea are significantly improved by using the described methods.

Preparation and catalytic performance of CuO-znO-AlO3/clinoptilolite nanocatalyst for single-step synthesis of dimethyl ether from syngas as a green fuel.

Direct conversion of syngas to dimethyl ether was successfully carried out over a clinoptilolite supported nanocatalyst modified by NH4Cl. A series of bifunctional nanocatalysts, CuO-ZnO-Al2O3 (CZA) over Clinoptilolite with different loading of CZA, were prepared via coprecipitation method and their catalytic performance were compared in a fixed-bed high pressure reactor. The catalysts were characterized by XRD, BET, FESEM, FTIR and TPD-NH3 techniques. The physicochemical analysis showed that with NH4CI treatment, the specific surface area of clinoptilolite increased obviously, while its crystallinity decreased slightly. It was found that the crystallinity of clinoptilolite was dramatically changed, whereas crystallinity of CuO has not been influenced significantly by the increase of CZA content. Moreover, with increasing the CZA/Clinoptilolite ratio, the specific surface area of nanocatalysts decreased. It is shown that the CZA particle size is distributed between 30.5-131.2 nm with an average size of 70.6 nm in which 77.8% of the particles are in the range of below 100 nm. The TPD-NH3 patterns showed that the number of the acid sites of the nanocatalysts decreased with the increase the CZA content. The influence of reaction pressure was investigated, confirming that the optimal reaction pressure for this catalyst was 40 bar. The catalytic performance is shown that the CZA/Clinoptilolite = 2 nanocatalyst had higher activity, selectivity due to its higher acidic sites.

Mild and general palladium-catalyzed synthesis of methyl aryl ethers enabled by the use of a palladacycle precatalyst.

A general method for the Pd-catalyzed coupling of methanol with (hetero)aryl halides is described. The reactions proceed under mild conditions with a wide range of aryl and heteroaryl halides to give methyl aryl ethers in high yield.

Asymmetric total synthesis of fusarentin 6-methyl ether and its biomimetic transformation into fusarentin 6,7-dimethyl ether, 7-O-demethylmonocerin, and (+)-monocerin.

A concise asymmetric total synthesis of a fusarentin ether (1) with sequential biomimetic transformation to its analogues fusarentin 6,7-dimethyl ether (2), 7-O-demethylmonocerin (3), and (+)-monocerin (4) has been accomplished. The cis-fused furobenzopyranones of 7-O-demethylmonocerin (3) and (+)-monocerin (4) were efficiently constructed via an intramolecular nucleophilic trapping of a quinonemethide intermediate, which was obtained by benzylic oxidation of fusarentin 6-methyl ether (1) using hypervalent iodine reagent.

Influence of a methyl substituent on the Raman spectrum of but-3-enyl methyl ether.

The Raman spectrum of but-3-enyl methyl ether, CH(2)CHCH(2)CH(2)OCH(3) is reported and compared with those of its homologues in which a methyl group is substituted for a hydrogen atom on one of the carbon atoms of the alkenyl chain. Attention is focused on the influence of this methyl group on the bands in the spectrum associated with specific CH, skeletal stretching and bending vibrations. The use of ab initio DFT quantum mechanical calculations to assist in making these assignments reveals a high degree of mode-mixing in the skeletal vibrations. The value of model studies of this kind in refining the correlations between the presence and absence of specific bands in a Raman spectrum with molecular structure is emphasised.

Synthesis of the C19 methyl ether of aspercyclide A via germyl-Stille macrocyclisation and ELISA evaluation of both enantiomers following optical resolution.

Aspercyclide A (1) is a biaryl ether containing 11-membered macrocyclic natural product antagonist of the human IgE-FcεRI protein-protein interaction (PPI); a key interaction in the signal transduction pathway for allergic disorders such as asthma. Herein we report a novel approach to the synthesis of the C19 methyl ether of aspercyclide A, employing a Pd(0)-catalysed, fluorous-tagged alkenylgermane/arylbromide macrocyclisation (germyl-Stille reaction) as the key step, and evaluation of both enantiomers of this compound via ELISA following optical resolution by CSP-HPLC. A crystal structure for germyl hydride 27 is also reported.

[Methoxymethyl and (p-nitrobenzyloxy)methyl groups in the synthesis of oligoribonucleotides by the phosphotriester method].

An efficient synthetic method for monomer ribonucleotide synthons containing 2'-O-methoxymethyl and 2'O-(p-nitrobenzyloxy)methyl groups used for oligonucleotide phosphotriester method with O-nucleophilic intramolecular catalysis at the stage of formation of internucleotide bond is developed. It is shown that synthons containing protecting 2'-O-(p-nitrobenzyloxy)methyl group may be used for automatic synthesis of phosphotriester oligoribonucleotides with high yields and synthons containing methoxymethyl group--to get 2'-O-modified oligonucleotides.

Asymmetric synthesis and biological evaluations of (+)- and (-)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels.

An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of L-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (-)- and racemic isomers.

An easily accessible Re-based catalyst for the selective conversion of methanol: evidence for an unprecedented active site structure through combined operando techniques.

Heterogeneous Re/SiO(2) catalysts prepared using a one pot sol-gel synthesis were found to display high activity in the direct, selective methanol conversion to methylal, which is correlated to an unprecedented rhenium oxide structure.

Synthesis of long-chain [¹8F]Deoxyfluoropoly(ethylene glycol) methyl ethers and their noninvasive pharmacokinetic analysis by positron emission tomography.

[¹8F]DeoxyfluoroPEG methyl ethers with an average molecular weight of 2 kDa ([¹8F]1a) and 10 kDa ([¹8F]1b) were synthesized by the fluorination of the tosylates 3a,b with [¹8F]nBu4NF at 80°C for 20 min followed by flash filtration through a Sep-Pak Plus Alumina-N cartridge. After the intravenous administration of [¹8F]1a and [¹8F]1b to rats, their pharmacokinetics was analyzed by noninvasive, real-time, whole-living-body monitoring using positron imaging technology. The effect of PEG's molecular weight on their blood circulation and organ clearance were quantitatively visualized for the first time.