Drug targeting to sites of oxidative stress using the Baeyer-Villiger reaction

The antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) is a desirable therapeutic target for a broad range of pathologies, including chronic diseases of the lung and liver, and autoimmune, neurodegenerative, and cardiovascular disorders. However, current Nrf2 activators are limited by unwanted effects due to non-specificity, and systemic distribution and action. Here we report that a 1,2-dicarbonyl moiety masks the electrophilic reactivity of the Nrf2 activator monomethyl fumarate (MMF), otherwise responsible for its non-specific effects. The 1,2-dicarbonyl compound is highly susceptible to Baeyer-Villiger oxidation, with generation of MMF specifically on exposure to pathological levels of hydrogen peroxide or peroxynitrite. Oral treatment with the MMF generating 1,2-dicarbonyl compound reversed chronic neuropathic and osteoarthritis pain in mice, and selectively activated Nrf2 at sites of oxidative stress. This 1,2-dicarbonyl platform may be used to treat additional disorders of oxidative stress, and to selectively target other therapeutics to sites of redox imbalance.

Catalytic asymmetric Nakamura reaction by gold(I)/chiral N,Nʹ-dioxide-indium(III) or nickel(II) synergistic catalysis

Intermolecular addition of enols and enolates to unactivated alkynes was proved to be a simple and powerful method for carbon-carbon bond formation. Up to date, a catalytic asymmetric version of alkyne with 1,3-dicarbonyl compound has not been realized. Herein, we achieve the catalytic asymmetric intermolecular addition of 1,3-dicarbonyl compounds to unactivated 1-alkynes attributing to the synergistic activation of chiral N,N′-dioxide-indium(III) or nickel(II) Lewis acid and achiral gold(I) π-acid. A range of β-ketoamides, β-ketoesters and 1,3-diketones transform to the corresponding products with a tetra-substituted chiral center in good yields with good e.r. values. Besides, a possible catalytic cycle and a transition state model are proposed to illustrate the reaction process and the origin of chiral induction based on the experimental investigations.

Microbial Synthesis of (S)- and (R)-Benzoin in Enantioselective Desymmetrization and Deracemization Catalyzed by Aureobasidium pullulans Included in the Blossom Protect™ Agent

In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect™ agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 °C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.

Catalytic asymmetric Nakamura reaction by gold(I)/chiral N,Nʹ-dioxide-indium(III) synergistic catalysis

Intermolecular addition of enols and enolates to unactivated alkynes was proved to be a simple and powerful method for carbon-carbon bond formation. Up to date, a catalytic asymmetric version of alkyne with 1,3-dicarbonyl compound has not been realized. Herein, we achieve the first catalytic asymmetric intermolecular addition of 1,3-dicarbonyl compounds to unactivated 1-alkynes. A range of β-ketoamides with a cyclic all-carbon quaternary center and acyclic quaternary center with a fluorine substituent were synthesized in excellent yields with good enantioselectivities attributing to the synergistic activation of chiral N,N′-dioxide-indium(III) Lewis acid and achiral gold(I) π-acid. Besides, a possible catalytic cycle and transition state models were proposed to illustrate the origin of process based on the experimental investigations.

MoO3 Nanoparticles as an Efficient Catalyst for the Synthesis of Pyrazoles in Aqueous-alcoholic Medium at Room Temperature

We have successfully explored the potential MoO3 nanoparticles as a heterogeneous catalyst for the cyclocondensation of hydrazines/hydrazides with 1,3-dicarbonyl compound in aqueousalcoholic medium at room temperature. The present method has been developed using green chemistry measures and offers a range of N-substituted pyrazoles with moderate to excellent yields. Utilization of non-toxic catalyst, wide substrate scope and environmentally benign reaction medium are the important features of the developed protocol. Interestingly, MoO3 nanocatalyst can easily be recovered from the reaction mixture and showed excellent reusability with a modest change in product yield. We have reported herein the synthetic pathway with less disastrous effect in the atmosphere.

Recent Advances in the Synthesis of Pyrroles

: Pyrroles are the most prevalent heterocyclic compounds, which are present as the basic cores in many natural products, such as vitamin B12, bile pigments like bilirubin and biliverdin, the porphyrins of heme, chlorophyll, chlorins, bacteriochlorins, and porphyrinogens. The biological activities of compounds having pyrrole analogs include antimicrobial (antibacterial, antifungal), anti-cancer (anti-cytotoxic, antimitotic), anti-tumor, anti-hyperlipidemic, anti-depressant, anti-inflammatory, antihyperglycemic, antiproliferative, anti-HIV and anti-viral activities. Accordingly, significant attention has been paid to develop competent methods for the synthesis of pyrroles with improved yields in short times. This review gives an overview of different methods for the synthesis of pyrrole using easily available precursors using the following routes. . Synthesis of monosubstituted pyrrole using 2,5-dimethoxyfuran . Synthesis of pyrrole using dialkylacetylene dicarboxylate . Synthesis of pyrroles using β-ketoester . Synthesis of pyrrole using 1,2-dicarbonyl compounds . Synthesis of pyrroles using 1,3-dicarbonyl compounds . Synthesis of pyrroles using 1,3-dicarbonyl, amine, nitro and aldehyde group . Synthesis of pyrroles using 1,4-dicarbonyl compound and amines . Synthesis of pyrrole using enones . Synthesis of pyrroles using moieties having acetylene group