Heterogeneous Catalysis to Drive the Waste-to-Pharma Concept: From Furanics to Active Pharmaceutical Ingredients

A perspective on the use of heterogeneous catalysis to drive the waste-to-pharma concept is provided in this contribution based on the conversion of furanics to active pharmaceutical ingredients (APIs). The provided overview of the concept in this perspective article has been exemplified for two key molecule examples: Ancarolol and Furosemide

Cytosine Palladium Complex Supported on Ordered Mesoporous Silica as Highly Efficient and Reusable Nanocatalyst for One-Pot Oxidative Esterification of Aldehydes

The synthesis of esters is one of the most fundamental and significant subjects in organic chemistry and chemical industry because they are used in high-value products such as cosmetics, biofuel, pharmaceuticals, surfactants, and food ingredients. In this study, an efficient, economic, sustainable, and green protocol for oxidative esterification reaction has been developed. A one-pot direct transformation of aliphatic, aromatic, and unsaturated aldehydes into esters in the presence of oxygen has been carried out over mesoporous organosilica-supported palladium nanocatalyst (Pd-Cyt@SBA-15) under ambient conditions. Pd-Cyt@SBA-15 efficiently catalyzed selectively large-scale conversion of aldehydes into esters in high yields and large turnover numbers (TON = 98,000). Pd-Cyt@SBA-15 nanocatalyst demonstrated excellent reusability and stability and could be recycled up to ten times without loss of significant reactivity. ICP-AES analysis showed that no leaching of active palladium species occurred during the recycling process of the heterogeneous Pd-Cyt@SBA-15 nanocatalyst

Efficient synthesis of imino-1,3-thiazinan-4-one promoted by acetonitrile electrogenerated base and computational stadies with CB1 and 11 βHSD1 molecules

The publication was prepared with the support of the PFUR Program “5–100”

Annelated medium-sized azaheterocycles as attractive scaffolds for CNS targeted leads.

Medium-sized nitrogen heterocycles (7-to-15-membered) have widespread interest in organic synthesis and medicinal chemistry. Indeed, such heterocyclic rings are found as subunits or core structures in natural and bioactive molecules, including pharmaceutical products, whereas on the other hand they often can serve as key intermediates in the synthesis of bicyclic compounds by selective transformations (e.g., transannular ring-contractions, cycloadditions). These molecular frameworks, particularly annelated 7-to-10-membered aza-heterocycles, have long drawn our attention as potential scaffolds for developing new multitarget- directed ligands (MTDLs) for treating Alzheimer's disease (AD) and other neurodegenerative syndromes.AD, the most common form of dementia affecting people worldwide, is a progressive neurodegenerative disorder, whose multifactorial pathogenesis is still not completely understood. The main histopathological changes include synaptic dysfunction and neuronal loss resulting from intracellular and extracellular fibrillar aggregates of Beta-amyloid (Abeta),hyperphosphorilated and beta-folded tau proteins, cholinergic impairment, oxidative stress, neuroinflammation, metal dys-homeostasis and mitochondrial damage. Among others, N- methyl-D-aspartate receptors (NMDARs) play a major role in learning and memory, and their overactivation causes excessive calcium influx and consequent excitotoxicity, which is associated with CNS diseases, including Parkinson's disease. Starting from our old1,2 and recent 3 findings on the suitability of partially hydrogenated benzo-, chromane-4- one- and indole-fused azepine and azocine derivatives targeted at enzymes, receptors and biochemical pathways involved in the pathogenesis of AD, we extended the investigation to novel derivatives of annelated azonines and azecines. Herein, our recent advances of benzo- and indol-fused 7-to-10-membered nitrogen heterocycles as molecular tools for AD-associated targets (e.g., butyryl- and acetylcholinesterase, monoamine oxidases A and B, Abeta aggregation, ROS insult, NMDAR antagonist), along with the results from investigation on cell and ex vivo/in vivo animal models, will be presented and discussed in an effort of rationalizing structure-activity relationships and progressing drug optimization of the examined CNS-targeted lead compounds

8H-Chromeno[2′,3′:4,5]imidazo[2,1-a]isoquinoline

The title compound, C18H12N2O, comprises two aromatic fragments, viz., imidazo[2,1-a]isoquinoline and benzene, linked by oxygen and methyl­ene bridges. Despite the absence of a common conjugative system within the mol­ecule, it adopts an essentially planar conformation with an r.m.s. deviation of 0. 036 Å. In the crystal, due to this structure, mol­ecules form stacks along the b axis by π⋯π stacking inter­actions, with shortest C⋯C distances in the range 3.340 (4)–3.510 (4) Å. The mol­ecules are bound by inter­molecular C—H⋯O inter­actions within the stacks and C—H⋯π inter­actions between the stacks

Synthesis of 8-phenyl substituted 3-benzazecines with allene moiety, their thermal rearrangement and evaluation as acetylcholinesterase inhibitors

Various 4′-R-substituted phenyl azacyclic allenes were synthesized in good yields, and their thermal transformations were studied. For the first time, the obtained rearrangement products—new N-bridged cyclopenta[a]indenes, and the corresponding parent allenes were evaluated as potential inhibitors of acetyl- and butyrylcholinesterase. Among the tested compounds, the allene derivative 2g proved to competitively inhibit human AChE with inhibition constant value (Ki) in the low micromolar range. Graphic abstract: [Figure not available: see fulltext.

Homobivalent Lamellarin-Like Schiff Bases: In Vitro Evaluation of Their Cancer Cell Cytotoxicity and Multitargeting Anti-Alzheimer's Disease Potential

Marine alkaloids belonging to the lamellarins family, which incorporate a 5,6-dihydro-1-phenylpyrrolo[2,1-a]isoquinoline (DHPPIQ) moiety, possess various biological activities, spanning from antiviral and antibiotic activities to cytotoxicity against tumor cells and the reversal of multidrug resistance. Expanding a series of previously reported imino adducts of DHPPIQ 2-carbaldehyde, novel aliphatic and aromatic Schiff bases were synthesized and evaluated herein for their cytotoxicity in five diverse tumor cell lines. Most of the newly synthesized compounds were found noncytotoxic in the low micromolar range (<30 μM). Based on a Multi-fingerprint Similarity Search aLgorithm (MuSSeL), mainly conceived for making protein drug target prediction, some DHPPIQ derivatives, especially bis-DHPPIQ Schiff bases linked by a phenylene bridge, were prioritized as potential hits addressing Alzheimer's disease-related target proteins, such as cholinesterases (ChEs) and monoamine oxidases (MAOs). In agreement with MuSSeL predictions, homobivalent para-phenylene DHPPIQ Schiff base 14 exhibited a noncompetitive/mixed inhibition of human acetylcholinesterase (AChE) with Ki in the low micromolar range (4.69 μM). Interestingly, besides a certain inhibition of MAO A (50% inhibition of the cell population growth (IC50) = 12 μM), the bis-DHPPIQ 14 showed a good inhibitory activity on self-induced β-amyloid (Aβ)1-40 aggregation (IC50 = 13 μM), which resulted 3.5-fold stronger than the respective mono-DHPPIQ Schiff base 9

Post-Ugi Cyclization for the Construction of Diverse Heterocyclic Compounds: Recent Updates

Multicomponent reactions (MCRs) have proved as a valuable tool for organic and medicinal chemist because of their ability to introduce a large degree of chemical diversity in the product in a single step and with high atom economy. One of the dominant MCRs is the Ugi reaction, which involves the condensation of an aldehyde (or ketone), an amine, an isonitrile, and a carboxylic acid to afford an α-acylamino carboxamide adduct. The desired Ugi-adducts may be constructed by careful selection of the building blocks, opening the door for desired post-Ugi modifications. In recent times, the post-Ugi transformation has proved an important synthetic protocol to provide a variety of heterocyclic compounds with diverse biological properties. In this review, we have discussed the significant advancements reported in the recent literature with the emphasis to highlight the concepts and synthetic applications of the derived products along with critical mechanistic aspects

Three-Component Reaction of 3-Arylidene-3H-Indolium Salts, Isocyanides, and Alcohols

A novel isocyanide-based multicomponent synthesis of alkyl aryl(indol-3-yl)acetimidates has been established. Starting from aryl(indol-3-yl)methylium tetrafluoroborates, aromatic isocyanides and alcohols, the imidates were obtained in moderate to very good yields. Consecutive four-component synthesis of the above mentioned imidates from N-alkylindoles, aromatic aldehydes, aromatic isocyanides and alcohols was also proposed. In addition, it was shown that in the presence of water, aryl(indol-3-yl)methylium tetrafluoroborates reacted with isocyanides to furnish aryl(indol-3-yl)acetamides

Six-membered ring systems: with O and/or S atoms

A large variety of publications involving O- and S-6-membered ring systems have appeared in 2017. The importance of these heterocyclic compounds is highlighted by the huge number of publications on the total synthesis of natural oxygen derivatives and of other communications dedicated to synthetic derivatives. Reviews on stereoselective organocatalytic synthesis of tetrahydropyrans (17EJO4666), of tetrahydropyrans and their application in total synthesis of natural products (17CSR1661), on the synthesis of the less thermodynamically stable 2,6-trans-tetrahydropyrans (17S4899), on enantioselective synthesis of polyfunctionalized pyran and chromene derivatives (17TA1462), and on enantioselective and racemic total synthesis of camptothecins, including the formation of their pyran-2-one ring (17SL1134), have appeared. Advances in the transition metal-catalyzed synthesis of pyran-2/4-ones (17TL263), N-heterocyclic carbene (NHC)-catalyzed achiral synthesis of pyran-2-one, coumarin and (thio)chromone derivatives (17OBC4731), on the synthesis and transformation of 2H-pyran-2-ones (17T2529) and 2-styrylchromones (17EJO3115) into other heterocyclic compounds, have been surveyed. The strategies to build up the tetrahydropyranyl core of brevisamide (17H(95)81) and the reactions of ketyl radicals, generated from carbonyl derivatives under transition-metal photoredox-catalyzed conditions, leading to isochromen- and chroman-type compounds (17CC13093) were disclosed. Developments in the synthesis of pentafluorosulfanyl(chromene and coumarin) derivatives (17TL4803), photoswitchable D9-tetrahydrocannabinol derivatives (17JA18206), and aminobenzopyranoxanthenes with nitrogen-containing rings (17JOC13626) have been studied.info:eu-repo/semantics/publishedVersio