Heck reaction over palladium supported on nickel ferrite as an efficient and inexpensive catalyst

1549-1554The palladium supported on nickel ferrite found to be highly active catalyst for the Heck olefination of aryl iodides and activated aryl bromides providing an excellent yield in an aerobic condition, in shorter reaction time

Studies on phosphine free Pd-salen complexes as effective catalysts for aqueous Suzuki reaction

565-572 Palladium complexes of the salen ligands, N,N'-bis(salicylidene)-ethylenediamine and N,N'-bis(salicylidene)-1,2-phenylenediamine have been explored for their catalytic activity in a phosphine-free aqueous Suzuki reaction. The various reaction parameters have been systematically optimized with respect to various solvents, bases, temperatures and Pd concentrations. The studies conclude that 1:1 DMF to water solvent ratio, Na2CO3 as base and 0.5 mol% of palladium at 90°C is apt for Suzuki reactions. Rapid transformation of substituted aryl iodides and aryl bromides into corresponding biaryls has been observed with excellent yield ranging from 70-86%, under optimized conditions. </smarttagtype

An Efficient Cost-Effective Removal of Ca²⁺, Mg²⁺, and Cu²⁺ Ions from Aqueous Medium Using Chlorosodalite Synthesized from Coal Fly Ash

Fly ash is one of the coal combustion solid wastes which causes environmental problems around the world. In this context for the first time, this paper reports the conversion of coal fly ash (CFA) into aluminosilicate chlorosodalite, Na₈[AlSiO₄]₆Cl₂. The synthesized chlorosodalite was analyzed by X-ray diffraction, Fourier transform infrared, scanning electron microscopy, and Brunauer–Emmett–Teller surface area measurements. The synthesized aluminosilicate chlorosodalite material was tested for potential applications for the removal of calcium, magnesium, and copper from their aqueous medium. The catch method was successfully used to study the effect of the initial concentration of metal ions, adsorbent dose, and contact time. The equilibrium data obtained were fitted by the Langmuir, Freundlich, Temkin, and Dubinin–Radushkevich isotherm models and showed the affinity order Cu²⁺ > Ca²⁺ > Mg²⁺. The well-known thermodynamic aspects such as the variation in Gibbs free energy (Δ<i>G</i>), entropy (Δ<i>S</i>), and enthalpy (Δ<i>H</i>) were also evaluated. Further the kinetic parameters including the rate constant and the order of sorption process were also determined

Synthesis of Novel Aryl and Heteroaryl Acyl Sulfonimidamides via Pd-Catalyzed Carbonylation Using a Nongaseous Precursor

Hitherto unexplored aryl and heteroaryl acyl sulfonimidamides have been prepared through the development of a new Pd-catalyzed carbonylation protocol. This novel methodology, employing sulfonimidamides as nucleophiles and CO gas <i>ex situ</i> released from solid Mo(CO)₆ in a sealed two-chamber system, yields a wide range of carbamate protected acyl sulfonimidamides in good to excellent yields

Total synthesis of (±)-coerulescine and (±)-horsfiline

Wittig olefination–Claisen rearrangement protocol was applied to obtain 3-allyl oxindole. This oxindole was then converted to (±)-coerulescine and (±)-horsfiline

Zeolite catalyzed solvent-free one-pot synthesis of dihydropyrimidin-2(1H)-ones – A practical synthesis of monastrol

A zeolite-catalyzed, simple, one-pot, solvent-free, cost effective, and environmentally benign process for the synthesis of dihydropyrimidones is described. This reaction is scaleable to multigram scale and the catalyst is recyclable. This methodology has resulted in an efficient synthesis of monastrol, a potent inhibitor of kinesin Eg5

NUDT15-mediated hydrolysis limits the efficacy of anti-HCMV drug ganciclovir

Ganciclovir (GCV) is the first-line therapy against human cytomegalovirus (HCMV), a widespread infection that is particularly dangerous for immunodeficient individuals. Closely resembling deoxyguanosine triphosphate, the tri-phosphorylated metabolite of GCV (GCV-TP) is preferentially incorporated by the viral DNA polymerase, thereby terminating chain extension and, eventually, viral replication. However, the treatment outcome of GCV varies greatly among individuals, therefore warranting better understanding of its metabolism. Here we show that NUDT15, a Nudix hydrolase known to metabolize thiopurine triphosphates, can similarly hydrolyze GCV-TP through biochemical studies and co-crystallization of the NUDT15/GCV-TP complex. More critically, GCV efficacy was potentiated in HCMV-infected cells following NUDT15 depletion by RNAi or inhibition by an in-house-developed, nanomolar NUDT15 inhibitor, TH8321, suggesting that pharmacological targeting of NUDT15 is a possible avenue to improve existing anti-HCMV regimens. Collectively, the data further implicate NUDT15 as a broad-spectrum metabolic regulator of nucleoside analog therapeutics, such as thiopurines and GCV

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo