Ring-rearrangement metathesis of substituted dihydropyrans and dihydrofurans

The rearrangement of dihydropyrans and dihydrofurans featuring appending olefins has been studied. The rearranged products bear resemblance with polyunsaturated di- and trisaccharides. Examples of functionalization prior to, or following, rearrangement are provided suggesting that the method should be useful for the synthesis of nonclassical saccharides. This work also illustrates the power of cascade methatetic processes for increasing molecular complexity starting from relatively simple heterocycles.     

An efficient approach to the stereoselective synthesis of 2,6-disubstituted dihydropyrans via stannyl-Prins cyclization

A general method has been developed for the stereoselective construction of 2,6-disubstituted dihydropyrans based on the Lewis acid-catalyzed intramolecular reactions of oxocarbenium ions with vinylstannanes. This novel methodology was applied to the enantioselective total synthesis of (−)-centrolobine.     

Highly enantioselective synthesis of α-trichloromethyldihydropyrans catalyzed by bifunctional organocatalysts

The enantioselective Michael addition of α-cyanoketones to α,β-unsaturated trichloromethyl ketones was firstly reported. With a phenylalanine-derived bifunctional piperazine/thiourea catalyst, a series of α-trichloromethyldihydropyrans were obtained with up to 95% ee and 99% yield.     

Novel synthesis of dihydropyrans and 2,8-dioxabicylo[3.3.0]oct-3-enes using Mn(III)-based oxidative cyclization

The Mn(III)-based reaction of 1,1-disubstituted alkenes with 2-(2-oxoethyl)malonates and 3-acetylpentane-1,4-diones gave novel substituted dihydropyrans and 2,8-dioxabicyclo[3.3.0]oct-3-enes in good yields, respectively. These routes rely on the nucleophilic character of the carbonyl-oxygen atoms of the malonates and pentanediones used to obtain the products by a cycloaddition reaction or cycloaddition-tandem cyclization reactions.     

One-pot multicomponent synthesis of 2,3-dihydropyrans: new access to furanose-pyranose 1,3-C-C-linked-disaccharides

An efficient synthesis of 2,3-dihydropyrans from different terminal alkynes was developed. The 2,3-dihydropyrans were obtained in a few minutes through a microwave-assisted multicomponent enyne cross-metathesis/hetero-Diels-Alder reaction. Starting from C-ethynyl-ribofuranose, a new multicomponent approach to furanose-pyranose 1,3-C-C-linked disaccharides was also developed.     

Excellent treatment activity of biscoumarins and dihydropyrans against P. aeruginosa pneumonia and reinforcement learning for designing novel inhibitors

Pseudomonas aeruginosa (P. aeruginosa) is a common clinical pathogen, which can easily cause cystic fibrosis and even bacteremia. In recent years, the antibiotic resistance of P. aeruginosa has been increasing. In an attempt to develop novel antibacterial agents, a series of biscoumarins (1–5) and dihydropyrans (6–10) were successfully prepared. The molecular structures of two representative compounds, that is, 1 and 6 were confirmed by single crystal X-ray diffraction study. The anti-bacterial activity of these synthesized compounds in vitro was evaluated by measuring the MIC values, as well as the P. aeruginosa growth curves. Next, the in vivo treatment activity of these compounds against the P. aeruginosa pneumonia infection was assessed by observing the survival rate of the infected mice and counting the bacterial load with colony plate counting assay. Additionally, the ELISA detection was conducted to evaluate the inflammatory response levels by measuring the IL-1β and TNF-α content released into the plasma, nasal lavage fluid and alveolar lavage fluid. The HE staining was also carried out to detect the protective effect of the compounds on the lung tissue damage. Further, novel anti-bacterial structures that are based on biscoumarin 5 are predicted and evaluated using reinforcement learning technic, and two outstanding pharmaceutical structures with low binding energy and high SA and QED scores are analyzed in detail using molecular docking simulation.     

First example of the activation of polymethylhydrosiloxane with molecular iodine: a facile synthesis of 3,6-dihydropyran derivatives

Glycals react rapidly with polymethylhydrosiloxane (PMHS) in the presence of a catalytic amount of molecular iodine under mild conditions to afford the corresponding 3,6-dihydropyran derivatives in excellent yields. Et₃SiH/I₂ was also found to be effective for this conversion.     

InBr3-catalyzed stereoselective synthesis of trans-2,6-disubstituted 3,6-dihydro-2H-pyrans

A new method for the stereoselective synthesis of trans-2,6-disubstituted 3,6-dihydro-2H-pyrans with a variety of substitution patterns is described, involving Lewis acid induced tandem allylation or cyanation of δ-hydroxy-α,β-unsaturated aldehydes to produce dihydropyrans in good yields and with trans-selectivity. This method is very useful for the synthesis of trans-2,6-disubstituted dihydropyran ring-containing natural products such as laulimalide, scytophycin C and many others.     

Relative thermodynamic stabilities of the isomeric dihydrofurans and isomeric dihydropyrans. An experimental and DFT study

The relative thermodynamic stabilities of 2,5-dihydrofuran (1) and 2,3-dihydrofuran (2), and of 3,4-dihydro-6H-pyran (3) and 3,4-dihydro-2H-pyran (4), were determined at several temperatures by base-catalyzed equilibration in DMSO solution. For 1 → 2, = –15.4±0.1 kJ mol⁻¹, =–12.6±0.5 kJ mol⁻¹, and =9.5±1.3 J K⁻¹ mol⁻¹ at 298.15 K. The second-law reaction enthalpy agrees with literature data based on calorimetric enthalpies of hydrogenation of the isomeric forms in hexane. For 3 → 4, =–19.3±0.2 kJ mol⁻¹, = –18.9±1.1 kJ mol⁻¹ and =1.1±3.0 J K⁻¹ mol⁻¹ at 298.15 K: the experimental reaction enthalpy is in marked disagreement with literature data based on estimation. On the other hand, both of the experimental reaction enthalpies of the present study are in good agreement with DFT calculations using the B3LYP functional and 6-311+G(2d,p) basis set.