Dehydrohelicene-based molecules stand out as highly promising scaffolds and captivating chiroptical materials, characterized by their unique chirality. Their quasi-helical π-conjugated molecular ...architecture, featuring successively
-annulated aromatic rings, endows them with remarkable thermal stability and optical properties. Over the past decade, diverse approaches have emerged for synthesizing these scaffolds, reinvigorating this field, with anticipated increased attention in the coming years. This review provides a comprehensive overview of the historical evolution of dehydrohelicene chemistry since the pioneering work of Zander and Franke in 1969 and highlights recent advancements in the synthesis of various molecules incorporating dehydrohelicene motifs. We elucidate the intriguing structural features and optical merits of these molecules, occasionally drawing comparisons with their helicene or circulene analogs to underscore the significance of the bond between the helical termini.
Autoxidation of aldehydes to peracids and carboxylic acids holds a significant impact in both academia and industry due to their wide applications in organic synthesis and environmental remediation. ...However, the multiple pathways involved in this reaction have hindered the development of sustainable methods for peracid synthesis. Herein, we conduct a comprehensive kinetic and mechanistic investigation to elucidate the interplay between these pathways. Subsequently, we introduce an efficient eco-friendly method to oxidize aldehydes to their corresponding peracids under sunlight or UV irradiation using oxygen as the sole oxidant without any additives or photocatalysts. Additionally, we demonstrate a simple method for the autoxidation of aldehydes to carboxylic acids
via
controlling key parameters such as the wavelength and solvent. These methods exhibit broad applicability to aromatic and aliphatic aldehydes, successful scaling up to the gram scale, and utilizing renewable solar energy making them good alternatives for traditional methods.
Autoxidation of aldehydes to peracids and carboxylic acids holds a significant impact in both academia and industry due to their wide applications in organic synthesis and environmental remediation.
A novel double aza-oxa7helicene was synthesized from the commercially available
,
-di(naphthalen-2-yl)benzene-1,4-diamine and
-benzoquinone in two steps. Combining the acid-mediated annulation with ...the electrochemical sequential reaction (oxidative coupling and dehydrative cyclization) afforded this double hetero7helicene. Moreover, the structural and optical features of this molecule have been studied using X-ray crystallographic analysis, and the absorption and emission behaviors were rationalized based on DFT calculations.
The pursuit of chiral nanographenes with robust chiral stability and good chiroptical responses is of great interest for material-based applications. However, the most reported preparation processes ...involve intricate synthetic pathways and harsh conditions, resulting in readily epimerization due to their low epimerization barriers. In this study, we present a streamlined one-pot electrochemical synthesis for a novel double oxaza7dehydrohelicene, characterized by a substantial epimerization barrier (33.8 kcal mol−1) and notable chiroptical responses (|glum| = 1.5 × 10−3). To optimize the electrochemical conditions efficiently, we applied a Bayesian optimization (BO) approach with expected improvement (EI) or lower confidence bound (LCB) as an acquisition function, aiming to maximize exploration and exploitation while minimizing the number of experiments needed to identify global maxima. Additionally, the structural and optical features of this molecule have been studied using X-ray crystallographic analysis, and the absorption and emission behaviors were rationalized based on DFT calculations.
Traditional optimization methods using one variable at a time approach waste time and chemicals and assume that different parameters are independent from one another. Hence, a simpler, more ...practical, and rapid process for predicting reaction conditions that can be applied to several manufacturing environmentally sustainable processes is highly desirable. In this study, biaryl compounds were synthesized efficiently using an organic Brønsted acid catalyst in a flow system. Bayesian optimization-assisted multi-parameter screening, which employs one-hot encoding and appropriate acquisition function, rapidly predicted the suitable conditions for the synthesis of 2-amino-2'-hydroxy-biaryls (maximum yield of 96%). The established protocol was also applied in an optimization process for the efficient synthesis of 2,2'-dihydroxy biaryls (up to 97% yield). The optimized reaction conditions were successfully applied to gram-scale synthesis. We believe our algorithm can be beneficial as it can screen a reactor design without complicated quantification and descriptors.
Dehydrohelicenes are some of the most attractive chiroptical materials with unique helical chirality. However, to our knowledge, there are no prior reports on their direct construction by asymmetric ...methods. In this work, sequential synthesis of aza-oxa-dehydro7helicenes via the electrochemical oxidative hetero-coupling of 3-hydoxycarbazoles and 2-naphthols followed by dehydrative cyclization and intramolecular C-C bond formation has been realized. In addition, an efficient enantioselective synthesis through chiral vanadium-catalyzed hetero-coupling and electrochemical oxidative transformations afforded heterodehydro7helicene without any racemization. The obtained dehydro7helicenes showed intense blue-colored circularly polarized luminescence (|g
| ≈ 2.5 × 10
at 433 nm). Thermodynamic and kinetic studies of the racemization barrier of heterodehydro7helicenes indicated significant chiral stability with ΔG
> 140 kJ mol
.
A diethylaminosulfur trifluoride (DAST)-mediated ring-opening reaction of cyclopropyl silyl ethers in nitriles produced allylic amides in moderate to good yields (up to 87%). Time course studies ...using ReactIR and O-isotopic labeling mechanistic studies suggested that the present reaction occurs via a Ritter-type process, leading to the formation of allylic amides.
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•Series of thieno2,3-dpyrimidines as Amuvatinib analogues were designed and synthesized.•Most of the newly synthesized compounds displayed a remarkable activity against (PANC-1) cell ...line.•3D-QSAR model was built up with five-featured pharmacophore (AAHHR).•ADME study was carried out to predict the pharmacokinetic properties.
Pancreatic cancer is one of the most challenging diseases with seven months only as median survival time due to its poor prognosis. Several enzymes are blamed for the progress of pancreatic cancer especially, platelet-derived growth factor receptors (PDGFRs), this in turn makes them promising targets for its treatment. In this study, twenty eight new compounds based on thieno2,3-dpyrimidine scaffold were synthesized as anti-pancreatic cancer agents mimicking the benzofuro3,2-dpyrimidine derivative, amuvatinib. Various linkers including amides, esters, ketones, urea and thiourea derivatives were utilized to study their effect on the anti-proliferative activity of these compounds. Most of the tested compounds revealed good cytotoxic activities against pancreatic carcinoma cell line PANC-1. Compound 9d showed the highest cytotoxicity with an IC50 value of 5.4 µM. Furthermore, 9d showed excellent platelet derived growth factor receptor (PDGFR-α) inhibitory activity, with IC50 value 0.155 µM. Docking study was carried out into PDGFR-α active site which showed comparable binding mode to that of FDA approved PDGFR-α inhibitor, imatinib. 3D-Quantitative structure activity relationship (QSAR) model was built up with five-featured pharmacophore which could be implemented for emerging effective lead structures. These compounds could serve as a new chemotype for discovering new agents for pancreatic cancer therapy.
The adjustment of the main helical scaffold in helicenes is a fundamental strategy for modulating their optical features, thereby enhancing their potential for diverse applications. This work ...explores the influence of helical elongation (n = 5–9) on the structural, photophysical, and chiroptical features of symmetric oxanhelicenes. Crystal structure analyses revealed structural variations with helical extension, impacting torsion angles, helical pitch, and packing arrangements. Through theoretical investigations using density functional theory (DFT) calculations, the impact of helical extension on aromaticity, planarity distortion, and heightened chiral stability were discussed. Photophysical features were studied through spectrophotometric analysis, with insights gained through time‐dependent DFT (TD‐DFT) calculations. Following optical resolution via chiral high‐performance liquid chromatography (HPLC), the chiroptical properties of both enantiomers of oxa7helicene and oxa9helicene were investigated. A slight variation in the main helical scaffold of oxanhelicenes from 7 to 9 induced an approximately three‐fold increase in dissymmetry factors with the biggest values of|glum| of oxa9helicene (2.2 × 10−3) compared to|glum|of oxa7helicene (0.8 × 10−3), findings discussed and supported by TD‐DFT calculations.
This work explores the influence of helical elongation of symmetric oxanhelicenes on their structural, photophysical, and chiroptical features via experimental and computational analysis. A slight variation in the helical scaffold induced around a three‐fold increase in dissymmetry factors from|glum| = 0.0008 for oxa7helicene to|glum| = 0.0022 for oxa9helicene.
This research aimed to improve water solubility and oral bioavailability of a newly synthesized thienopyrimidine derivative (TPD) with anti-pancreatic cancer activity by loading on starch ...nanoparticles (SNPs).
TPD was synthesized, purified and its ADME behavior was predicted using Swiss ADME software. A UV spectroscopy method was developed and validated to measure TPD concentration at various dosage forms. SNPs loaded with TPD (SNPs-TPD) were prepared, characterized for particle size, polydispersity index, zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), entrapment efficiency, in-vitro release, and in-vivo animal study.
The Swiss ADME results showed that TPD can be administered orally; however, it has low oral bioavailability (0.55) and poor water solubility. The significant regression coefficient of the calibration curve (r
= 0.9995), the precision (%RSD < 0.5%) and the accuracy (99.46-101.72%) confirmed the efficacy of the developed UV method. SNPs-TPD had a spherical monodispersed (PDI= 0.12) shape, nanoparticle size (22.98 ± 4.23) and good stability (-21 ± 4.72 mV). Moreover, FT-IR and DSC revealed changes in the physicochemical structure of starch resulting in SNPs formation. The entrapment efficiency was 97% ± 0.45%, and the in-vitro release showed that the SNPs enhanced the solubility of the TPD. The in-vivo animal study and histopathology showed that SNPs enhanced the oral bioavailability of TPD against solid Ehrlich carcinoma.
SNPs-TPD were superior in drug solubility and oral bioavailability than those obtained from TPD suspension.
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