The N-phenylquinoneimine scaffold is a versatile synthetic platform that has gained significant attention in the field of drug discovery due to its structural diversity and capacity to interact with biologically relevant targets. This review explores...
Chemical genetics is an approach for identifying small molecules with the ability to induce a biological phenotype or to interact with a particular gene product, and it is an emerging tool for lead generation in drug discovery. Accordingly, there is...
Diversity-Oriented Synthesis (DOS) represents a strategy to obtain molecule libraries with diverse structural features starting from one common compound in limited steps of synthesis. During the last two decades, DOS has become an unmissable strategy...
The piperidine ring is a widespread motif in several natural bioactive alkaloids of both vegetal and marine origin. In the last years, a diversity-oriented synthetic (DOS) approach, aimed at the generation of a library of piperidine-based derivatives...
The Nef reaction (nitro to carbonyl group conversion) and related Meyer reaction are among the key transformations of aliphatic nitro compounds. The interrupted versions of these reactions in which the normal pathway is redirected to a different end...
We are currently witnessing a decline in the development of efficient new anticancer drugs, despite the salient efforts made on all fronts of cancer drug discovery. This trend presumably relates to the substantial heterogeneity and the inherent biolo...
How can diversity-oriented strategies for chemical synthesis provide chemical tools to help shape our understanding of complex cancer pathways and progress anti-cancer drug discovery efforts? This review (surveying the literature from 2003 to the pr...
The Ugi four-component reaction (Ugi-4CR) undoubtedly is the most prominent multicomponent reaction (MCRs) that has sparked organic chemists’ interest in the field. It has been widely used in the synthesis of diverse heterocycle molecules such...
One of the goals of diversity-oriented synthesis is to achieve the structural diversity of obtained compounds. As most biologically active compounds are chiral, it is important to develop enantioselective methods of their synthesis. The application o...
We have recently reported a novel multicomponent reaction between arylacetic acids and isocyanides, affording α-acyloxyacrylamides through an unusual mechanism. The products of this novel multicomponent reaction can rearrange to five membered heteroc...
The development of diversity-oriented synthesis based on fluorine-containing building blocks has been one of the hot research fields in fluorine chemistry. β-CF3-1,3-enynes, as one type of fluorine-containing building blocks, have attracted more...
Eighteen (2RS,6RS)-2-(4-methoxyphenyl)-6-(substituted ethyl)dihydro-2H-pyran-4(3H)ones were synthesized via a DDQ-mediated oxidative carbon-hydrogen bond activation reaction. Fourteen of these tetrahydropyrans were substituted with triazoles readily...
Polyfunctional building blocks are essential for the implementation of diversity-oriented synthetic strategies, highly demanded in small molecule libraries’ design for modern drug discovery. Acyl(imidoyl)ketenes are highly reactive organic compounds,...
Herein, advanced intermediates were synthesized through Ugi four-component reactions of isocyanides, aldehydes, masked amino aldehyde, and carboxylic acids, including N-protected amino acids. The presence of a masked aldehyde enabled acid-mediated de...
Oxidative fragmentation of tertiary cyclopropanols with phenyliodine(III) dicarboxylates in aprotic solvents (dichloromethane, chloroform, toluene) produces mixed anhydrides. The fragmentation reaction is especially facile with phenyliodine(III) reag...
Hydroxycinnamic acids represent a versatile group of dietary plant antioxidants. Oxidation of methyl-p-coumarate (pcm) and methyl caffeate (cm) was previously found to yield potent antitumor metabolites. Here, we report the formation of potentially b...
We report the synthesis of a very useful building block that could give pharmaceutical companies access to a series of novel calcitriol analogs, a library of compounds. This approach is called Diversity-Oriented Synthesis (DOS).
Fluorine represents a privileged building block in pharmaceutical chemistry. Diethylaminosulfur-trifluoride (DAST) is a reagent commonly used for replacement of alcoholic hydroxyl groups with fluorine and is also known to catalyze water elimination a...
Substrate-controlled diversity-oriented synthesis of polycyclic frameworks via [4 + 2] and [3 + 2] annulations between ninhydrin-derived Morita–Baylis–Hillman (MBH) adducts and 3,4-dihydroisoquinolines under similar reaction conditions ha...
Considering the potential bioactivities of natural product and natural product-like compounds with highly complex and diverse structures, the screening of collections and small-molecule libraries for high-throughput screening (HTS) and high-content s...
Small-molecule probes are powerful tools for studying biological systems and can serve as lead compounds for developing new therapeutics. Especially, nitrogen heterocycles are of considerable importance in the pharmaceutical field. These compounds ar...
The construction of a small molecule library that includes compounds with medium-sized rings is increasingly essential in drug discovery. These compounds are essential for identifying novel therapeutic agents capable of targeting “undruggable&r...
A collection of smart multicomponent reactions (MCRs) with continuative post condensation cyclizations (PCCs) is presented to construct conventional three- to seven-membered heterocyclic compounds in diversity oriented syntheses (DOS). These will pro...
The application of the reagent-based diversification strategy for generation of libraries of biologically promising β-lactam derivatives is described. Key features are the versatility of the linker used and the cross-metathesis functionalization...
Hepatitis B virus (HBV) is a causative reagent that frequently causes progressive liver diseases, leading to the development of acute hepatitis, chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma. Despite several antiviral drugs, i...
Quinazoline is a privileged heterocyclic scaffold commonly found in numerous pharmaceuticals and bioactive natural products, known for its diverse biological activities. The pursuit of efficient and versatile synthetic methods to produce quinazoline...
A series of thirteen xanthones 3–15 was prepared based on substitutional (appendage) diversity reactions. The series was structurally characterized based on their spectral data and HRMS, and the structures of xanthone derivatives 1, 7, and 8 we...
Signal transducer and activator of transcription 3 (STAT3) is a validated anticancer target due to the relationship between its constitutive activation and malignant tumors. Through a virtual screening approach on the STAT3-SH2 domain, 5,6-dimethyl-1...
This review focuses upon the use of nitroso Diels–Alder reactions as a structural complexity generating reaction that has been so far a quite scarcely treated topic, despite its potential. In particular, the use of N-acyl-1,2-dihydropyridines a...
The generation of natural product-like compound collections has become an important area of research due to low hit rates found with synthetic high-throughput libraries. One method of generating compounds occupying the areas of chemical space not acc...
Tetrazoles have been widely studied for their biological properties. An efficient route for large-scale synthesis of 1,5-disubstituted tetrazoles (1,5-DTs) is presented. The strategy exploits a reductive approach to synthetize a cyclic chiral imine s...
A highly efficient approach to a new indolizine scaffold fused with pyrrolo[1,2-c]pyrimidine was achieved via one-pot three-component coupling followed by an oxidative cyclization reaction. The simple two-step sequence allowed rapid access to various...
A small set of twelve compounds of a nitrofuran carboxamide chemotype was elaborated from a readily available 2,6-diazaspiro[3.4]octane building block, exploring diverse variants of the molecular periphery, including various azole substituents. The i...
A Lewis acid-mediated three-component coupling reaction was successfully applied for the synthesis of lasofoxifene (1), nafoxidine (2), and their positional isomers, inv-lasofoxifene (3) and inv-nafoxidine (4). In the presence of HfCl4, the desired o...
Multicomponent reactions 9i.e., those that engage three or more starting materials to form a product that contains significant fragments of all of them), have been widely employed in the construction of compound libraries, especially in the context o...
2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-func...
With the widespread application and functional complexity of deep neural networks (DNNs), the demand for training samples is increasing. This elevated requirement also extends to DNN-based SAR object detection. Most public SAR object detection datase...
Modern advances in Chemical Biology include the improvement of screening methods, the introduction of bioinformatic methods to unravel biological pathways, and the generation of highquality chemical libraries. [...]
Hybridization of steroids and other pharmacophores often modifies the bioactivity of the parent compounds, improving selectivity and side effect profile. In this study, estradiol and 3′-(un)substituted benzisoxazole moieties were combined into...
Enantiomerically pure 2-substituted-2,5-dihydro-3-(aryl) sulfonyl/sulfinyl furans have been prepared from the easily accessible carbohydrate derivatives. The orientation of the substituents attached at the C-2 position of furans is sufficient to cont...
Glycoporphyrins are group of compounds of high value for the purpose of photodynamic therapy and other biomedical applications. Despite great progress in the field, new diversity-oriented syntheses of carbohydrate-porphyrin hybrids are increasingly d...
In this work we report the stereoselective synthesis of 2H-flavenes via an Aminocatalytic privileged Diversity-Oriented Synthesis (ApDOS) strategy. An oxa-Michael cyclization between salicylaldehydes and an iminium intermediate from cinnamaldehyde an...
N-containing heteroaromatics are important substructures found in numerous natural or synthetic alkaloids. The diversity of the structures encountered, as well as their biological and pharmaceutical relevance, have motivated research aimed at the dev...
Magnetic iron oxide nanoparticles (MIONPs) represent a versatile magnetic nanoparticle (NP) system with considerable, yet underexplored, potential in diverse applications, particularly in emerging biomedical fields such as magnetic resonance imaging,...
Enzyme catalysis is a very active research area in organic chemistry, because biocatalysts are compatible with and can be adjusted to many reaction conditions, as well as substrates. Their integration in multicomponent reactions (MCRs) allows for sim...
In the present paper, we report an efficient total synthesis of a marine alkaloid, rigidin E. The key tetrasubstituted 2-amino-3-carboxamidepyrrole intermediate was synthesized by cascade Michael addition/intramolecular cyclization between N-(2-(4-(b...
This work reports progress in the semi-synthetic modification of cassane-type diterpenes isolated from Coulteria platyloba, a plant of ethnopharmacological relevance. The approach involves a sequence of transformations, including oxidative aromatizat...
Multicomponent processes are beneficial tools for the synthesis of heterocycles. As densely substituted bifunctional electrophiles, ynones are essential intermediates by applying cyclocondensations or cycloadditions in numerous heterocycle syntheses....
In this study, we prepared oxizolidines through 1,3-bis(diphenylphosphino)-propane (DPPP)–catalyzed mixed double-Michael reactions of b-amino alcohols with electron-deficient acetylenes. These reactions are very suitable for the diversity-oriented pa...
The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis...
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