Fluorescent indicators for cytosolic sodium.

Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.

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Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells

Two new poly(p-phenylenevinylene) (PPV) derivatives bearing 2-phenyl-5-(4-tert-butylphenyl)-1,3,4-oxadiazole pendants were prepared, and their photo- and electroluminescence properties were studied. The first polymer (P-1) is poly[2-{4-[5-(4-tert-butylphenyl)-1,3,4-oxadiazolyl]phenyl}-1,4-phenylenevinylene], which is a PPV derivative having diphenyl-substituted 1,3,4-oxadiazole pendant that is known to be an excellent electron-transporting structure. The second polymer (P-2) is poly[2-{4-[5-(4-tert-butylphenyl)-1,3,4-oxadiazolyl]phenyl}-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]. The only structural difference between P-1 and P-2 is the presence of additional 2-ethylhexyloxy pendant groups in P-2. Both polymers were prepared by direct polymerization of the α,α‘-dibromo-p-xylene monomers having the pendant group(s) in the presence of excess potassium tert-butoxide. Both polymers reveal much improved electroluminescence (EL) properties when compared with PPV. They emit luminescence light over the wavelength...

Luminescence Properties of Structurally Modified PPVs: PPV Derivatives Bearing 2-(4-tert-Butylphenyl)-5-phenyl-1,3,4-oxadiazole Pendants

Nucleophilic addition to alkynes represents an attractive approach to the synthesis of olefins. Obstacles to this strategy include the low reactivity of alkynes toward many organometallic reagents and difficulties associated with controlling the regioselectivity of addition. Here we demonstrate that Fe(III) salts are effective precatalysts for the carbometalation of alkynes. Primary and secondary propargylic and homopropargylic alcohols react with alkyl and aryl Grignard reagents to provide Z-allylic and -homoallylic alcohols as single stereo and regioisomers. Alkylation and arylation occur distal to the alcohol. Common oxygen protecting groups and tertiary nitrogens are tolerated. The intermediate vinyl magnesium or iron species can be trapped with a variety of electrophiles including aldehydes, allyl bromide, and N-bromosuccinimide. Diyne substrates undergo an unusual addition/cyclization reaction to generate cyclic dienes. A brief discussion of mechanism is included.

Iron-Catalyzed Carbometalation of Propargylic and Homopropargylic Alcohols

In this account, we describe the design, synthesis and applications of tethered versions of the Ru(II)/N-tosyl-1,2-diphenylethylene-1,2-diamine (TsDPEN) class of catalyst that are commonly used for asymmetric transfer hydrogenation and asymmetric hydrogenation of ketones and imines. The review covers key aspects of the reaction mechanisms and examples of applications, including industrial applications to pharmaceutically important target molecules. In addition, closely related catalysts based on Rh(III) and Ir(III) are also described.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/tcr.201600084

The Development of Phosphine-Free "Tethered" Ruthenium(II) Catalysts for the Asymmetric Reduction of Ketones and Imines.

Le fait de placer un benzylether dans un systeme cyclique semble retarder de facon importante l'hydrogenolyse par rapport aux analogues acycliques

Substituent effects on hydrogenation of aromatic rings: hydrogenation vs. hydrogenolysis in cyclic analogs of benzyl ethers

Adenosine-derived ketone 5 was subjected to Noyori asymmetric transfer hydrogenation (ATH) using aqueous sodium formate as a stoichiometric reductant. Despite the well-known sensitivity of ATH to stereoelectronic effects from a contiguous stereogenic center, the 5′ stereochemistry was overwhelmingly controlled by the chirality of the catalyst. Both the (5′S,4′R) and the (5′R,4′R) diastereomers could be prepared selectively in good yields. An efficient three-step route that provides ketone 5 in 75% overall yield was developed.

Preparation of Both C5′ Epimers of 5′-C-Methyladenosine: Reagent Control Trumps Substrate Control

The present invention relates to the novel diastereoselective syntheses for generating phosphorothioate compounds. Examples include nucleoside phosphorothioate analogs that are useful in treating diseases and/or conditions such as viral infections.

Methods of stereoselective synthesis of substituted nucleoside analogs

Syntheses and equilibrations of 6- and 7-carbomethoxy-trans-2-oxadecalins

Oxidation reactions are critical components of the synthetic toolbox taught to undergraduate students during introductory organic chemistry courses. However, the oxidation reactions discussed in the undergraduate curriculum are often outdated as many organic chemistry textbooks emphasize chromium-based oxidants that are no longer in regular use by practitioners, which may limit an instructor’s time to allocate to discussion of other oxidants. Further, laboratory courses have since either removed oxidation experiments or replaced them with oxidative processes not discussed in lectures, thus leading to a disconnect between the two learning settings. As part of an effort to bridge this divide and modernize the oxidation reactions discussed in our curricula, we have developed a new laboratory experiment that uses a commercially available oxoammonium salt (Bobbitt’s salt) to cleanly oxidize cinnamyl alcohol to cinnamaldehyde. In addition to being a safe, convenient, colorimetric, and “green oxidant” suitable for use in the undergraduate teaching laboratory, the hydride-transfer mechanism allows for overlap with key course concepts presented in both introductory and advanced lecture courses. The procedure is well-suited for small and large organic I, II, or advanced laboratory sections alike and can be completed within a standard 3–4 h laboratory period. Aside from exposing students to a modern green oxidation protocol, the experiment contains expanded opportunities for interpretation of 1H NMR, 13C NMR, and IR spectra. An optional addendum for advanced students involving Hammett correlations was also developed. 

Luigi Anzalone

Papers

Substituent effects on hydrogenation of aromatic rings: hydrogenation vs. hydrogenolysis in cyclic analogs of benzyl ethers

Preparation of Both C5′ Epimers of 5′-C-Methyladenosine: Reagent Control Trumps Substrate Control

Methods of stereoselective synthesis of substituted nucleoside analogs

Syntheses and equilibrations of 6- and 7-carbomethoxy-trans-2-oxadecalins

A Practical Oxidation Experiment for Undergraduate Students: Bobbitt’s Salt as a “Green” Alternative