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The medicinal importance, natural rarity, and challenges associated with the synthesis of C3-functionalized 1 H -indazoles have propelled the development of novel and practical 1 H -indazole N-oxides for the production of diverse arrays of C3-functionalized 1 H -indazoles. The use of 1 H -indazole N-oxides has been remarkably effective for the selective introduction of diverse functional groups, including amino (NHAr), chloro (Cl), hydroxy (OH), sulfonyl (SO2 Ar), aromatic (Ar), olefin, alkyl, and N-formyl (NRCHO) groups, to indazole pharmacophore molecules. This review offers a concise overview of the synthetic approaches and practical applications of 1 H -indazole N-oxides, including recent studies conducted by the authors. Transformative reactions involving 1 H -indazole N-oxides not only offer strategies for synthesizing C3-functionalized 1 H -indazoles but also hold significant potential in medicinal chemistry. 1 Introduction 2 Synthetic Approaches and Applications of 1 H -Indazole N -Oxides 3 Summary and Outlook [ABSTRACT FROM AUTHOR]

Heterocyclic compounds are crucial for medicinal chemistry and the development of therapeutic agents like broad-spectrum antibiotics. This study devised a facile procedure to synthesize novel antimicrobial bicyclic heterocycles from 2-mercapto-3-phenylquinazolin-4(3H)-one. Advanced analytical techniques including 1H and 13C NMR, elemental analysis, and FT-IR spectroscopy characterized the intricate chemical structures of the products. In vitro assays tested the heterocycles against aerobic and anaerobic bacterial strains using fluconazole and ciprofloxacin as antifungal and antibacterial controls. Results demonstrated the formidable broad-spectrum antibacterial and antifungal activities of the synthesized compounds, with growth inhibition approaching that of the positive controls. These findings highlight the immense potential of these novel heterocyclic compounds as antimicrobial agents. Further research can optimize their drug-like properties for eventual clinical use in combating drug-resistant infections. [ABSTRACT FROM AUTHOR]

This document provides information on the synthesis and characterization of various compounds belonging to the imidazo[2,1-b][1,3]thiazine family. The compounds were synthesized using a specific method and characterized using various techniques such as NMR and HRMS. The document includes details on the physical properties, yields, and spectral data of each compound. The document also acknowledges the contribution of M. Malikėnas for HRMS measurements and provides a link to supporting information. [Extracted from the article]

In this research, two novel series of dibenzo[b,f]azepines (14 candidates) were designed and synthesised based on the rigidification principle and following the reported doxorubicin's pharmacophoric features. The anti-proliferative activity was evaluated at the NCI against a panel of 60 cancer cell lines. Further, the promising candidates (5a–g) were evaluated for their ability to inhibit topoisomerase II, where 5e was noticed to be the most active congener. Moreover, its cytotoxicity was evaluated against leukaemia SR cells. Also, 5e arrested the cell cycle at the G1 phase and increased the apoptosis ratio by 37.34%. Furthermore, in vivo studies of 5e showed the inhibition of tumour proliferation and the decrease in its volume. Histopathology and liver enzymes were examined as well. Besides, molecular docking, physicochemical, and pharmacokinetic properties were carried out. Finally, a SAR study was discussed to open the gate for further optimisation of the most promising candidate (5e). Two novel series of dibenzo[b,f]azepines were designed and synthesised based on the rigidification principle in drug design. The anti-proliferative activity was evaluated at the NCI against a panel of 60 cancer cell lines. 5e was the most active anti-topo II congener (IC50 = 6.36 ± 0.36 µM). 5e was evaluated against leukaemia SR cells and its cytotoxic effect was confirmed (IC50 = 13.05 ± 0.62 µM). In vivo studies of 5e significantly inhibited tumour proliferation by 62.7% and decreased tumour volume to 30.1 mm3 compared to doxorubicin treatment. [ABSTRACT FROM AUTHOR]

The [1,2,4]triazolo[4,3-a]pyridine derivative 3-(4-(benzyloxy)-3-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine was prepared in a 73% isolated yield by means of an oxidative ring closure of a hydrazine intermediate. Sodium hypochlorite was used as the oxidant and ethanol as a solvent, making the process a clean, green approach. The reaction was performed at room temperature for 3 h, and then the heterocycle was isolated in an analytically pure form by extraction, followed by passing the crude product mixture through a small plug of alumina. [ABSTRACT FROM AUTHOR]

1,2,5-Chalcogenadiazoles fused with electron-withdrawing heterocycles have been actively investigated for the preparation of organic photovoltaic materials. [1,2,5]Oxadiazolo[3,4-d]pyridazines are much less studied than other chalcogenadiazolopyridazines due to their low availability. In this communication, we report our study showing that 5,6-dihydro-[1,2,5]oxadiazolo[3,4-d]pyridazine-4,7-dione, a key precursor for the synthesis of 4,7-dihalo-[1,2,5]oxadiazolo[3,4-d]pyridazines, is formed via the cyclization of 1,2,5-oxadiazole-3,4-dicarbohydrazide in hydrochloric acid. The structure of the newly synthesized compound was established by means of elemental analysis; high-resolution mass spectrometry; 1H and 13C NMR; IR spectroscopy, and mass spectrometry. [ABSTRACT FROM AUTHOR]

5-Alkenyl hydantoins and alkenyl spirohydantoins are converted into bicyclic and tricyclic hydantoins, under indirect electrochemical conditions, generating the phenylselenyl cation in situ. The reactions proceeded in good to exelent yields. The influence of electrochemical conditions on regioand diastereoselectivity of the selenocyclization reactions is investigated. [ABSTRACT FROM AUTHOR]

The intramolecular Heck reaction is a well-established strategy for natural product total synthesis. When constructing large rings, this reaction is also referred to as Heck macrocyclization, which has proved a viable avenue to access diverse naturally occurring macrocycles. Less noticed but likewise valuable, it has created novel macrocycles of non-natural origin that neither serve as nor derive from natural products. This review presents a systematic account of the title reaction in forging this non-natural subset of large rings, thereby addressing a topic rarely covered in the literature. Walking through two complementary sections, namely (1) drug discovery research and (2) synthetic methodology development, it demonstrates that beyond the well-known domain of natural product synthesis, Heck macrocyclization also plays a remarkable role in forming synthetic macrocycles, in particular macrocyclic drugs. [ABSTRACT FROM AUTHOR]

Decomposition of the polycation Al 13 O 4 (OH) 24 (H 2 O) 12 7+ (Al 13) promoted by ligand is a vital subject to advance our understanding of natural and artificial occurrence and evolution of aluminum ions, especially in the case of acidic condition that dissolved Al3+ species can be released from the Al-bearing substances. However, the microscopic pathway of synchronous proton-promoted and ligand-promoted decomposition process for Al 13 is still in the status of ambiguity. Herein, we applied differential mass spectrometry method and DFT calculation to study the initial detailed process of Al 13 decomposition under the presence of proton and salicylic acid (H 2 Sal). Mass results showed that the mononuclear Al3+-H 2 Sal complexes dominated the resulting Al species, whereas the monodentate complex Al 13 HSal6+ was not observed in the spectra. The difference of decomposition levels between the ligand/Al ratio 0.2 and 0.5 cases revealed that proton and ligand performed synergistic effect in initial Al 13 decomposition process, and the proton transfer determined the ring closure efficiency. The ring closure reaction is the prerequisite for the collapse of Al 13 structure and detachment of the mononuclear complex. DFT calculations reveal that hydrogen bond plays an important role in inducing the formation of chelated complex accompanying proton transfer. Attachment of protons at the bridging OH− can elongate and weaken the critical bond between targeted Al3+ and µ 4 -O2- resulting from delocalization of electron pairs in the oxygen atom. These results demonstrate the detailed mechanism of Al 13 composition promoted by ligand and proton, and provide significant understanding for further application and control of Al 13. [Display omitted] [ABSTRACT FROM AUTHOR]

The process of midazolam ring closure was studied from the thermodynamic and kinetic points of view by means of quantum-chemical methods. B3LYP/6–311 + + G(d,p) model was employed for gas phase and water environment (polarizable continuum model) calculations. It was concluded that the reaction rate determining step is the first step—carbinolamine formation from amine and carbonyl ends of the opened benzodiazepine ring. The Gibbs free energy of activation was calculated as 35.1 kcal/mol for gas- phase and 33.9 kcal/mol for water environment. Intrinsic reaction coordinate calculations were performed to verify that the transition state really connects the substrate and product. Thermodynamically, this reaction is endoergic with ΔG = 9.6 kcal/mol for gas phase and 10.0 kcal/mol for water environment. However, the next step—carbinolamine protonation with immediate water molecule loss is expected to be fast and activation barrierless, which enables further progress of the ring closure, despite the positive ΔG of the fist step. Next, the protonated imine undergoes deprotonation to final closed ring, pharmacologically active molecule of midazolam. The whole chain of reaction is exoergic with ΔG equal to − 5.6 kcal/mol for gas phase and − 7.7 kcal/mol for water environment. In order to understand the role of other than benzodiazepine/imidazole molecular fragments on the ring closure process, a model was build which contains only benzodiazepine and imidazole rings. The activation barrier for the carbinolamine formation of the model is similar to midazolam in the gas phase but higher by about 10 kcal/mol for water environment. The most interesting difference is however that for the model, the carbinolamine formation step is exoergic with ΔG equal to − 2.2 kcal/mol for gas phase and − 1.8 kcal/mol for water environment. This difference can be connected to complicated conformational shape of the midazolam molecule, which during the ring closure undergoes unfavorable deformations with accompanying rise of the energy of the molecule. The protonation sites for both midazolam and the model were also studied. In the case of midazolam, the preferred protonation site is the imidazole ring nitrogen atom, but in the case of the model it is the benzodiazepine ring nitrogen atom. The aromaticity of the 5- and 7-membered rings were analyzed using two aromaticity—HOMA and pEDA. It follows that larger stability of the cation protonated at the benzodiazepine ring is accompanied with substantial increase of the 7-ring aromaticity in the model of midazolam. The complexes of midazolam and its model with a water molecule were analyzed because they are needed for evaluation of the energy of the whole process of ring closure. In the case of midazolam, the water molecule preferentially connects to imidazole ring, but in the case of the model, complexes with both imidazole and benzodiazepine rings have similar stability. [ABSTRACT FROM AUTHOR]

A convenient domino synthetic approach for the construction of the indolizidine core in diastereoselective manner has been developed from inexpensive starting compounds, providing triple functionalization. The novel synthetic route started from β-lactam derived from 1,5-cyclooctadiene including a ring-opening metathesis/cross-metathesis sequence as key steps with methyl acrylate followed by intramolecular ring closure across an aza-Michael addition. The process gave functionalized indolizidine framework with stereocontrol in high yields. DFT calculations supported the experimentally observed stereoselective reaction. [ABSTRACT FROM AUTHOR]

An efficient radical cyclization of suitably functionalized ynamides to nitrogen-containing heterocycles is reported. Upon reaction with tributyltin hydride in the presence of catalytic amounts of AIBN in toluene at 80 °C, a range of ynamides bearing a N -iodopropyl chain could be smoothly cyclized, in a highly regio- and stereoselective manner, to the corresponding 2-arylidenepyrrolidines in good to excellent yields. The exocyclic double bond was in addition shown to be an excellent anchor for further chemical diversification and the generality of this radical cyclization could be highlighted by its extension to the synthesis of other nitrogen heterocycles including piperidines, azepanes, pyrazolidines and hexahydropyridazines. [ABSTRACT FROM AUTHOR]

In the course of the synthesis of fused-ring analogues of the antidepressant drug tianeptine, representatives of three new heterocyclic ring systems, indolo[1,7- bc ][1,2]benzothiazepines (and their 4,5-dihydro analogues), 5,6-dihydroquino[1,8- bc ][1,2]benzothiazepines, and [1,2]benzothiazepino[4,3,2- jk ]carbazoles, as well as their intermediates, have been prepared. The tetracyclic and pentacyclic ring systems containing either an oxo or a hydroxy functional group are suitable for introducing various side chains, including potential pharmacophores. For this latter transformation, examples are demonstrated by conversion of the hydroxy group into a chloro moiety and subsequent reaction with amines or with primary alcohols bearing a tertiary amino side chain. Two fused-ring derivatives exhibiting the side-chain characteristics of tianeptine have also been synthesized. Altogether 40 compounds are described in the present manuscript, eight of them are also characterized by single-crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

The significant pharmacological activity of 2,3-benzodiazepine-4-ones led to an increased interest in this compound family. However, the literature of the closely related 2,3,4-benzothiadiazepine 2,2-dioxides is rather scarce. Earlier we elaborated a synthesis of 5-aryl congeners variously substituted at the aromatic ring. In the present study, a new synthetic route was investigated via highly versatile intermediates, to extend the reaction to a wider aromatic substitution pattern and to the preparation of 5-alkyl and 5-H derivatives. The essence of this approach is, starting from benzaldehyde acetals, acetophenone and benzophenone ketals, to synthesize ortho -formyl- and ortho -acyl-arylmethanesulfonyl chlorides, which are suitable precursors of the target compounds. The synthesis was implemented as follows: ortho -lithiation of the corresponding acetals and ketals and subsequent treatment with paraformaldehyde, or alternatively in two steps, with DMF or ethyl formate, followed by reduction with NaBH4 , led to the corresponding hydroxymethyl derivatives. Reaction of these latter with methanesulfonyl chloride gave mesylates that were used to S -alkylate thiourea to afford S -alkylisothiouronium salts. The final steps of the synthesis were carried out in a telescoped reaction. Treatment of the S -alkylisothiouronium salts with N -chlorosuccinimide resulted in the corresponding arylmethanesulfonyl chlorides. Subsequent reaction with hydrazine hydrate followed by an acidic treatment gave 2,3,4-benzothiadiazepine 2,2-dioxides. [ABSTRACT FROM AUTHOR]

Density functional theory is used to study ring closure HSCH2CH2S- and HSCH2CH2CH2S-. The transition state for ring closure of HSCH2CH2S- is predicted to be three-membered and for HSCH2CH2CH2S- is four-membered. Geometries are optimized using a 3-21G basis set. Calculated charges using B3LYP density functional shows that TS1 has more ionic character than TS2. The reactions are found to be endothermic. The activation energy for HSCH2CH2S- is smaller than HSCH2CH2CH2S.- [ABSTRACT FROM AUTHOR]

The present review describes the methodologies reported for the synthesis of 1,3‐diazepine derivatives. This heterocyclic moiety forms the core structure of many compounds with potent biological activities. Synthetic strategies by ring closure or ring transformation are discussed. [ABSTRACT FROM AUTHOR]

Functionally substituted 1,2-benzisoxazoles are very important and promising heterocycles with various pharmacological activities. Benzoxazoles containing reactive 3-chloromethyl and 5-amino groups are practically unexplored derivatives in this series. In this communication, the simple method for the synthesis of N-[3-(chloromethyl)-1,2-benzisoxazol-5-yl]acetamide which is an interesting precursor for the preparation of a series of 3,5-disubstituted benzoxazoles was described. The structure of the synthesized compound was established by elemental analysis, high-resolution mass spectrometry, 1H, 13C NMR and IR spectroscopy, and mass spectrometry.

Over the past few years, great progress has been made in the development of high‐affinity adenosine A1 and/or A2A receptor antagonists—promising agents for the potential treatment of Parkinson's disease. Unfortunately, many of these compounds raise structure‐related concerns. The present study investigated the effect of ring closures on the rA1/A2A affinity of compounds containing a highly reactive α,β‐unsaturated carbonyl system, hence providing insight into the potential of heterocycles to address these concerns. A total of 12 heterocyclic compounds were synthesised and evaluated in silico and in vitro. The test compounds performed well upon qualitative assessment of drug‐likeness and were generally found to be free from potentially problematic fragments. Most also showed low/weak cytotoxicity. Results from radioligand binding experiments confirm that heterocycles (particularly 2‐substituted 3‐cyanopyridines) can replace the promiscuous α,β‐unsaturated ketone functional group without compromising A1/A2A affinity. Structure–activity relationships highlighted the importance of hydrogen bonds in binding to the receptors of interest. Compounds 3c (rA1Ki = 16 nM; rA2AKi = 65 nM) and 8a (rA1Ki = 102 nM; rA2AKi = 37 nM), which both act as A1 antagonists, showed significant dual A1/A2A affinity and may, therefore, inspire further investigation into heterocycles as potentially safe and potent adenosine receptor antagonists. [ABSTRACT FROM AUTHOR]

A new and unexpected Rh(I)-catalyzed cycloisomerization of 1,6-enynes is reported. Several different alkyne substitution patterns were evaluated under the reaction conditions, including a deuterated derivative that provides some insight into the reaction mechanism.

New heterocyclic systems containing 1,2,5-chalcogenadiazoles are of great interest for the creation of organic photovoltaic materials and biologically active compounds. In this communication, 3,6-dibromopyridazine-4,5-diamine was investigated in reaction with selenium dioxide in order to obtain 4,7-dibromo-[1,2,5]selenadiazolo[3,4-d]pyridazine. We found that 7-bromo-[1,2,5]selenadiazolo[3,4-d]pyridazin-4(5H)-one, the first representative of the new heterocyclic system, was isolated as a hydrolysis product of the corresponding 4,7-dibromoderivative. The structure of the newly synthesized compound was established by means of elemental analysis, high-resolution mass spectrometry, 1H, 13C NMR, IR and UV spectroscopy, and mass spectrometry.

Functionally substituted 1,2-benzisoxazoles are very important and promising heterocycles with various pharmacological activities. Benzoxazoles containing reactive 3-chloromethyl and 5-amino groups are practically unexplored derivatives in this series. In this communication, the simple method for the synthesis of N-[3-(chloromethyl)-1,2-benzisoxazol-5-yl]acetamide which is an interesting precursor for the preparation of a series of 3,5-disubstituted benzoxazoles was described. The structure of the synthesized compound was established by elemental analysis, high-resolution mass spectrometry, 1H, 13C NMR and IR spectroscopy, and mass spectrometry. [ABSTRACT FROM AUTHOR]

Abstract Biologically attractive azaspiro[4.5]trienones have been prepared via Ugi four-component reaction (Ugi-4CR) followed by bromine-mediated ipso-cyclization. This allows a straightforward synthetic route to a diverse collection of fully functionalized 3-bromoaza­spiro[4,5]trienones in moderate to good yields that can be used as templates for further modifications.

A new approach to the synthesis of 2-(pyrimidin-2-yl)benzoic acids based on the ring contraction of the 2-carbamimidoylbenzoic acid [(2-amidinobenzoic) acid] with 1,3-dicarbonyl compounds and their synthetic equivalents has been developed. The intramolecular condensation of the obtained acids with 1,3-dielectrophiles proceeds with the formation of the 4,6-dihydropyrimido[2,1- a ]isoindole-4,6-dione system, the pyrrolidone ring of which is easily opened under the action of weak nucleophiles. The reaction of 2-amidinobenzoic acid with chromones, which have an aryloxy group at 3-position does not stop at the step of pyrimidine ring formation and undergoes further spontaneous cyclization into 2-(benzo[4,5]furo[3,2- d ]pyrimidin-2-yl)benzoic acids. [ABSTRACT FROM AUTHOR]

Benzene-1,3,5-tricarboxylic acid-functionalized MCM-41 (MCM-41-Pr-BTA), as a novel hybrid organosilica, was prepared and properly characterized by the Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller, thermal gravimetric analysis and energy-dispersive X-ray spectroscopy to evaluate the functional groups, crystallinity, surface area, morphology, particle size distribution and loading of functional groups. Interestingly, the 1,3-propylene linker used in this study incorporates appropriate catalytic activity into the MCM-41 framework compared to the more known trialkoxypropyl silanes. This new organosilica can be used as a hybrid nanocatalyst for the expeditious and efficient synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives, as an important pharmaceutical scaffold, in aqueous media via a three-component one-pot condensation of isatoic anhydride and aromatic aldehydes with primary amines or ammonium salts. This method has several advantages such as low catalyst loading, high to excellent yields, short reaction times, working under green conditions and simple workup. [ABSTRACT FROM AUTHOR]

Cyclopropenone 1,3-propanediol ketal is an increasingly versatile building block for the introduction of various C3 and dioxaspiro units due to the emergence of numerous methodologies for the application of strained hydrocarbons. This Practical Synthetic Procedure gives an updated synthesis for a basic ketal of cyclopropenone with lowered solvent toxicity and a detailed step-by-step guide for the safe production of potassium amide in liquid ammonia and for its application in the synthesis of the cyclopropene ring. [ABSTRACT FROM AUTHOR]

2-Pyridone is characterized by a very wide range of reactivity of a different nature, ranging from electrophilic aromatic substitution, CH–metal-mediated reactions, and NH/OH functionalization of both possible lactam/lactim tautomers, through cycloaddition, to nucleophilic addition and transformation of the tautomeric C=O/C–OH moiety. The high availability of 2-pyridones and the possibility of their far-reaching functionalization additionally increased their values. Therefore, they are very useful building blocks for the synthesis of structurally diverse piperidine and pyridine compounds, including naturally occurring 2-pyridones. This review reports on the use of simple 2-pyridones in the synthesis of alkaloids and alkaloids-inspired compounds based on the piperidine or pyridine framework. 1 Introduction 2 Structure, Availability, and Reactivity of 2-Pyridones 3 Monocyclic Piperidine Alkaloids from 2-Pyridones 4 Polycyclic Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds from 2-Pyridones 4.1 New Ring Formation Involving C/N Atoms of the 2-Pyridone Ring 4.1.1 Indolizine-Fused 2-Pyridones: Camptothecins and Related Compounds 4.1.2 Other Indolizines from 2-Pyridones 4.1.3 Compounds Bearing the Quinolizine Ring System 4.2 New Ring Formation Involving C/C Atoms of the 2-Pyridone Ring 4.2.1 C-2/C-3 Ring Fusion 4.2.2 C-3/C-4 Ring Fusion 4.2.3 C-4/C-5 Ring Fusion 4.2.4 C-5/C-6 Ring Fusion 4.2.5 C-2/C-4 Ring Bridge 4.2.6 C-2/C-6 Ring Bridge 4.2.7 C-3/C-5 Ring Bridge 4.2.8 C-3/C-6 Ring Bridge 4.2.9 C-4/C-6 Ring Bridge 5 Conclusion [ABSTRACT FROM AUTHOR]

Al/P‐ and Ga/P‐based frustrated Lewis pairs (FLPs) reacted with an azirine under mild conditions under cleavage of the heterocycle on two different positions. Opening of the C−C bond yielded an unusual nitrile–ylide adduct in which a C−N moiety coordinated to the FLP backbone. Cleavage of a C−N bond afforded the thermodynamically favored enamine adduct with the N atom bound to P and Al or Ga atoms. Ring closure was observed upon treatment of an Al/P FLP with electronically unsaturated substrates (4‐(1‐cyclohexenyl)‐1‐aza‐but‐1‐en‐3‐ynes) and yielded by C−N bond formation hexahydroquinoline derivatives, which coordinated to the FLP through P−C and Al−C bonds. Diphenylcyclopropenone showed a diverse reactivity, which depending on steric shielding and the polarizing effect of Al or Ga atoms afforded different products. An AltBu2/P FLP yielded an adduct with the C=O group coordinated to P and Al. The dineopentyl derivative gave an equilibrium mixture consisting of a similar product and a simple adduct with O bound to Al and a three‐coordinate P atom. Both compounds co‐crystallize. The Ga/P FLP only formed the simple adduct with the same substrate. Rearrangement resulted in all cases in C3‐ring cleavage and migration of a mesityl group from P to a former ring C atom by C−C bond formation. Diphenylthiocyclopropenone (evidence for the presence of P=C bonds) and an imine derivative afforded similar products. [ABSTRACT FROM AUTHOR]

We report the photophysical properties of diarylethene‐based photoswitches (DAE) which were incorporated into the backbones of macrocyclic peptides of variable sizes (6, 10 and 14 amino acids: cDAE‐6, cDAE‐10, and cDAE‐14). The insertion leads to a consistent bathochromic shift in UV/Vis absorption bands, a considerable peptide‐size‐dependent fluorescence intensity increase (up to a factor of 1.7), and a drastically reduced photoisomerization efficiency leading to formation of the ring‐closed DAE fragment. The compounds were studied by time‐resolved photoinduced broadband absorption spectroscopy, revealing a ring closure reaction for the unconstrained DAE reference system and, to a lesser extent, for cyclic cDAE‐14. The smallest cyclic peptide cDAE‐6 does not undergo any photoisomerization process at all. Furthermore, the DAE fragment ring closure reaction in the reference system is concurrent with intersystem crossing that is complete within a few picoseconds. Further analysis showed dominant triplet absorption throughout the observed spectral window (350–700 nm) in all macrocyclic systems. As a consequence, ring closure is favored in the unconstrained system in contrast to the cyclic peptides. Our studies demonstrate the importance of understanding the population dynamics of DAE rotamers when designing efficiently photocontrollable diarylethene‐based peptidomimetics. [ABSTRACT FROM AUTHOR]

• T3P® was used in a Robinson – Gabriel synthesis. • Efficient synthesis of bacterial and unnatural 5-(3-indolyl)oxazoles. • Avoid the use of toxic and hazardous water scavengers. In the present work, a propylphosphonic anhydride (T3P®) assisted Robinson–Gabriel cyclization of N -acyl-β-oxotryptamines for the synthesis of 2-substituted-5-(3-indolyl)oxazoles has been developed. The reactions proceeded smoothly in acetonitrile under microwave irradiation, and the product isolation required only an extraction and subsequent crystallization; no chromatography was necessary. The desired products were obtained in good to excellent yields. [ABSTRACT FROM AUTHOR]

Background Laparoscopic hernial repair is increasingly adopted even for neonates and has achieved a high success rate with low recurrence rate with long-term follow-up. The main advantages of laparoscopy are no incision of the fascia, exploriation of the other side in case of bilateral hernia, and visualization and safeguarding of the vas deferens and the spermatic vessels. Moreover, it is advantageous over open technique in case of recurrent hernia. Different modalities of techniques have been used for repair such as needlescopic disconnection of hernia sac, flip flap technique, muscular arch repair, and ring closure. Aim The aim of this study was to evaluate the feasibility, advantages, and the outcome of laparoscopic ring closure for repair of the inguinal hernia in children as a preliminary experience in our institution. Patients and methods This prospective study included 30 patients with unilateral and bilateral congenital inguinal hernia who were subjected to laparoscopic repair in the age group of 6 weeks up to 4 years. We use ring closure technique. Results Thirty children met our inclusion criteria; among them, 26 were boys, in whom indirect inguinal hernia sacs were closed (18 right, five left, three bilateral), and in the four girls, all indirect inguinal hernia sacs were closed. Currently, the median operating time for a unilateral hernia is 23 min (range: 19–40 min) and for bilateral hernias is 28 min (range: 25–55 min). There were no complications. Postoperative hydroceles occurred in three boys. Recurrence encountered in two (6.7%) cases. Conclusion The current series shows the feasibility of laparoscopic hernia repair in pediatric patients. Further technical refinement is needed to facilitate its applicability. Even if not used routinely, laparoscopy is a valuable tool for the objective evaluation and management of congenital inguinal hernia in children with advantage of being exploratory and curative with low recurrence and complications rate. [ABSTRACT FROM AUTHOR]

[Display omitted] Cyclohex-2-enones have aroused great interest among chemists due to their wide natural occurrence and readily accessible functionalizations. Therefore, multiple synthetic methods have been developed for the construction of the cyclohex-2-enone ring. It has been found that some derivatives with a cyclohex-2-enone structure as the core nucleus exhibit a wide range of pharmacological activities, including anti-cancer, anti-bacterial, anti-inflammatory, anti-oxidative and anti-neuropathic properties. In this mini review, we summarize the synthetic methodology and exploration of biological activities of cyclohex-2-enone derivatives based on literatures especially reported in recent several years, which provides a reference for the comprehensive and systematic study of these compounds for medicinal purposes. [ABSTRACT FROM AUTHOR]

A novel stereocontrolled approach has been developed for the syntheses of tashiromine and epitashiromine alkaloids from cyclooctene β-amino acids. The synthetic concept is based on the azetidinone opening of a bicyclic β-lactam, followed by oxidative ring opening through ring C–C double bond and reductive ring-closure reactions of the cis- or trans-cyclooctene β-amino acids.

Abstract N -aminopyridyl ketone salts were reacted with formamide to yield heteroaromatic pyrido[2,1- f ][1,2,4]triazinium salts. Upon storage of these products in the presence of water, formation of covalent hydrates have been observed. Reaction of the same starting compound with urethane yielded 3-chloropyrido[2,1- f ][1,2,4]triazinium salt which readily reacted with secondary amines to afford 3-amino derivatives. An analogous ring closure reaction of 2-formylaminomethyl- and formaminobenzylpyridine allowed the synthesis of the partially reduced 3,4-dihydropyrido[2,1- f ][1,2,4]triazinium compounds. The cyclization procedure was also applied for the synthesis of the related pyrimido[2,1- f ][1,2,4]triazinium salt. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

A palladium‐catalysed, phosphine‐free, direct arylation of 4‐phenoxyquinolines, in air is described. Using an intramolecular approach, the ring‐closed products are formed in yields of up to 95 %. This approach allows access to a range of benzofuroquinolines. An array of functional groups on both the quinoline and phenoxy rings are tolerated. A palladium‐catalysed, phosphine‐free, direct arylation of 4‐phenoxyquinolines in air is described. Using intramolecular direct arylation, the ring‐closed products are formed in isolated yields of up to 95 %. This approach allows access to a range of benzofuroquinolines, and an array of functional groups on both the quinoline and phenoxy rings is tolerated. [ABSTRACT FROM AUTHOR]

A novel synthetic approach was developed for the construction of the 1,2,3,4-tetrahydroisoquinoline framework possessing varied functions. The synthetic strategy was based on oxidative ring opening of some indene derivatives through their C=C bond, followed by double reductive amination of the dicarbonyl intermediates with various primary alkyl- or fluoroalkylamines. [ABSTRACT FROM AUTHOR]

Because of their biological relevance, cyclic β-amino acids have generated increasing interest and had significant impact in drug research over the past two decades. Their preparation and further functionalization towards new types of molecular entities have received large interest in synthetic and medicinal chemistry. Various types of metathesis reactions, such as ring-opening (ROM), ring-closing (RCM), or cross metathesis (CM) are used widely for access to either alicyclic β-amino acids or other densely functionalized derivatives of this group of compounds. This account intends to provide an insight into the most relevant synthetic routes to this class of derivatives with the application of metathesis reactions. The review focuses on the presentation of selective and stereocontrolled methodologies in view of versatility, robustness, limitations and efficiency. 1 Introduction 2 Synthesis and Transformation of Cyclic β-Amino Acids through Metathesis Reactions 2.1 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by Ring-Closing Metathesis 2.2 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by Cross Metathesis 2.3 Synthesis of β-Amino Acids with Larger Ring Systems by Ring- Closing Metathesis 2.4 Synthesis of β-Amino Acids with Condensed Ring Systems by Ring-Rearrangement Metathesis 2.5 Stereocontrolled One-Step Synthesis of Functionalized Cispentacin and Transpentacin Derivatives 2.5.1 Stereocontrolled Synthesis of Functionalized Cispentacin and Transpentacin Derivatives through Ring-Opening Metathesis of Norbornene β-Amino Acid Derivatives 2.5.2 Stereocontrolled Synthesis of Functionalized Azetidinones and β-Amino Acid Derivatives from Condensed Ring β-Lactams by Ring-Opening Metathesis 2.5.3 Carbon–Carbon Double Bond Functionalization of β-Amino Acid Derivatives and β-Lactams with α,β-Unsaturated Carbonyl Compounds through Cross Metathesis 2.5.4 Synthesis of Functionalized β-Amino Acid Derivatives and β-Lactams through Chemoselective Cross Metathesis 3 Conclusions and Outlook. [ABSTRACT FROM AUTHOR]

Abstract Heterocyclic nucleus plays a fundamental role in the medicinal chemistry and serves as a key template for the development of various therapeutic agents including broad spectrum antibacterial drugs. In an effort to develop new antibacterial agents, a bicyclic twelve-membered heterocyclic nucleus derived from coumarin was prepared by an uncomplicated method. The rate of ring closure for this nucleus, which was given the name coumacine, in addition to two of its derivatives was monitored spectroscopically and this rate followed zero order kinetics. The chemical structures of the synthesized products were established by detecting their physicochemical properties and analyzing their IR, 1H NMR and 13C NMR spectra. The in vitro antibacterial activity of coumacines was evaluated via agar dilution method against different standard aerobic and anaerobic bacterial strains using ciprofloxacin and metronidazole as positive controls, respectively; the results indicated that coumacine I has an excellent broad spectrum antibacterial activity against the tested bacterial strains with percentage of growth inhibition approximating to those of positive controls. [ABSTRACT FROM AUTHOR]

A new efficient synthesis of racemic anatabine is reported. The title target was obtained in an excellent overall yield of 70%, by a five-step synthesis, using cheap reagents and mild reaction conditions. [ABSTRACT FROM AUTHOR]

An improved and scalable synthesis of azulene has been developed by the application of pyrrolidine as a reagent and continuous steam distillation and extraction for workup. Applications for the coloration of perfluorinated media and silicones were demonstrated. [ABSTRACT FROM AUTHOR]

The C-nor-D-homo-steroidal alkaloid cyclopamine was discovered in the 1969 and in 2000 it was shown to act as an inhibitor of the hedgehog signaling (Hh) pathway, which is aberrantly activated in some tumors. Subsequently it was revealed that this natural occurring alkaloid has also antidiabetic and antiviral properties. In this review we present syntheses of selected C-nor-D-homo-steroidal alkaloids and their analogues and also discuss a general access to C-nor-D-homo-steroids. Some historical as well as biomedical aspects are also presented. 1 Introduction 2 Total Synthesis of Cyclopamine 2.1 Synthesis of exo-Cyclopamine and Further Cyclopamine Analogues 2.2 Synthesis of a Carbacyclopamine Analogue 3 D-Homocyclopamine: Saridegib (IPI-926) 4 Synthesis of Nakiterpiosin 5 Lewis Acid Mediated Nazarov Cyclization as a Versatile Method for C-Nor-D-homo-steroid Synthesis 6 Conclusion. [ABSTRACT FROM AUTHOR]

Established strategies for discovering selective kinase inhibitors are target-centric as they often target certain structural or reactive features in the target kinase. In the absence of such prominent features, there is a lack of general methods for discovering selective inhibitors. Here we describe a new strategy that exploits conformational flexibility of kinases for achieving selective kinase inhibition. Through ring closure, we designed and synthesized a panel of isoquinoline-containing compounds as rigidified analogs of an amidophenyl-containing parent compound. These analogs potently inhibit kinases including Abl and BRAF but have diminished inhibition against some other kinases compared to the parent compound. Sequence analysis reveals that many of the kinases that are potently inhibited by the isoquonoline-containing compounds contain a long insertion within their catalytic domains. A crystal structure of one rigid compound bound to BRAF confirmed its binding mode. Our findings highlight the potential of a novel strategy of rigidification for improving the selectivity of kinase inhibitors. [ABSTRACT FROM AUTHOR]

Previously synthesized 9-aryl-5 H-imidazo[2,1- d][1,2,5]triazepin-6(7 H)-ones have been used as starting materials for the synthesis of three new tricyclic ring systems, where an imidazotriazepine is condensed with an imidazole, triazole or tetrazole ring. These novel compounds could be potential drug candidates for central nervous system diseases because of their closely related structure to known tricyclic derivatives with anticonvulsant activity. Graphical Abstract : [ABSTRACT FROM AUTHOR]

A Michael-induced ring-closure (MIRC) strategy allowing the synthesis of 2-substituted aziridine-2-carboxylic esters is presented. A broad spectrum of nucleophiles can be applied, leading to large diversity of products which can be subjected to further structural modifications. Diastereoselective ring closure is observed in the case of chiral substrates. [ABSTRACT FROM AUTHOR]

Conjugate addition reactions of 2,4-pentandione, dibenzoylmethane and ethylacetoacetate to enones have been investigated using Amberlyst-15 or Amberlyst-15-DMAP acetate system as catalysts. When 2,4-pentandione reactions were carried out in the presence of Amberlyst-15, conjugate addition and/or conjugate-addition initiated ring closure products were obtained depending on the reaction conditions. However, unlike 2,4-pentandione, dibenzoylmethane gave only conjugate addition products with Amberlyst-15. When Amberlyst-15-DMAP acetate system was used, always only conjugate addition products were obtained with β-dicarbonyl compounds independent of the reaction conditions. [ABSTRACT FROM AUTHOR]