Heterocyclic Building Blocks-Tetrahydropyran

Machine Learning for Discovery of GSK3β Inhibitors was written by Vignaux, Patricia A.;Minerali, Eni;Foil, Daniel H.;Puhl, Ana C.;Ekins, Sean. And the article was included in ACS Omega in 2020.SDS of cas: 41340-25-4 This article mentions the following:

Alzheimer’s disease (AD) is the most common cause of dementia, affecting approx. 35 million people worldwide. The current treatment options for people with AD consist of drugs designed to slow the rate of decline in memory and cognition, but these treatments are not curative, and patients eventually suffer complete cognitive injury. With the substantial amounts of published data on targets for this disease, we proposed that machine learning software could be used to find novel small-mol. treatments that can supplement the AD drugs currently on the market. In order to do this, we used publicly available data in ChEMBL to build and validate Bayesian machine learning models for AD target proteins. The first AD target that we have addressed with this method is the serine-threonine kinase glycogen synthase kinase 3 beta (GSK3β), which is a proline-directed serine-threonine kinase that phosphorylates the microtubule-stabilizing protein tau. This phosphorylation prompts tau to dissociate from the microtubule and form insoluble oligomers called paired helical filaments, which are one of the components of the neurofibrillary tangles found in AD brains. Using our Bayesian machine learning model for GSK3β consisting of 2368 mols., this model produced a five-fold cross validation ROC of 0.905. This model was also used for virtual screening of large libraries of FDA-approved drugs and clin. candidates. Subsequent testing of selected compounds revealed a selective small-mol. inhibitor, ruboxistaurin(I), with activity against GSK3β (avg IC₅₀ = 97.3 nM) and GSK3α (IC₅₀ = 695.9 nM). Several other structurally diverse inhibitors were also identified. We are now applying this machine learning approach to addnl. AD targets to identify approved drugs or clin. trial candidates that can be repurposed as AD therapeutics. This represents a viable approach to accelerate drug discovery and do so at a fraction of the cost of traditional high throughput screening. In the experiment, the researchers used many compounds, for example, 2-(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid (cas: 41340-25-4SDS of cas: 41340-25-4).

2-(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid (cas: 41340-25-4) belongs to tetrahydropyran derivatives. Numerous natural products have tetrahydropyran skeleton as the building block for designing new natural products and their derivatives e.g. aplysiatoxins, avermectins, oscillatoxins, talaromycins, latrunculins and acutiphycins. There is large number of marine macrolide natural products that contain tetrahydropyran and tetrahydrofuran ring together. For instance, goniodomin A (actin targeting polyether), prorocentrolide (toxin halistatins), and percentotoxineSDS of cas: 41340-25-4

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Multi-omics reveal differentiation and maintenance of dimorphic flowers in an alpine plant on the Qinghai-Tibet Plateau was written by Zhu, Mingjia;Wang, Zhenyue;Yang, Yongzhi;Wang, Zefu;Mu, Wenjie;Liu, Jianquan. And the article was included in Molecular Ecology.Application of 17388-39-5 This article mentions the following:

Dimorphic flowers growing on a single individual plant play a critical role in extreme adaptation and reproductive assurance in plants and have high ecol. and evolutionary significance. However, the omics bases underlying such a differentiation and maintenance remain largely unknown. We aimed to investigate this through genomic, transcriptome and metabolomic analyses of dimorphic flowers in an alpine biennial, Sinoswertia tetraptera (Gentianaceae). A high-quality chromosome-level genome sequence (903 Mb) was first assembled for S. tetraptera with 31,359 protein-coding genes annotated. Two rounds of recent independent whole-genome duplication (WGD) were revealed. Numerous genes from the recent species-specific WGD were found to be differentially expressed in the two types of flowers, and this may have helped contribute to the origin of this innovative trait. The genes with contrasting expressions between flowers were related to biosynthesis of hormones, floral pigments (carotenoids and flavonoids) and iridoid compounds, which are involved in both flower development and color. Metabolomic analyses similarly suggested differential concentrations of these chems. in the two types of flowers. The expression interactions between multiple genes may together lead to contrasting morphol. and chem. concentration and open vs. closed pollination of the dimorphic flowers in this species for reproductive assurance. In the experiment, the researchers used many compounds, for example, (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5Application of 17388-39-5).

(4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5) belongs to tetrahydropyran derivatives. Tetrahydropyran is an important raw material and intermediate used in Organic Synthesis, Pharmaceuticals, Agrochemicals and dyestuff. The most notable anticancer agent, bryostatin, and eribulin are marine macrolides having intriguing tetrahydropyran and furan motif. Application of 17388-39-5

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Economically feasible strategy for confirmation of pharmaceuticals in hospital effluent using screening analysis was written by Cardoso, Renata M.;Dallegrave, Alexsandro;Becker, Raquel W.;Araujo, Debora S.;Sirtori, Carla. And the article was included in Analytical Methods in 2020.Formula: C17H21NO3 This article mentions the following:

The contamination of aquatic systems by pharmaceuticals has received considerable attention in recent decades, because these substances are increasingly detected in the environment. This is due to the abundant use of pharmaceuticals by the population and, consequently, their constant introduction into aquatic systems through domestic, industrial, and hospital wastewaters. Hospital effluents have highly complex compositions and present potential toxicity towards the environment. In this work, a screening methodol. was developed to evaluate the occurrence of pharmaceutical products in hospital wastewater, using a viable, easy, and economical strategy employing com. pharmaceutical compounds for screening anal. Six samplings of hospital wastewater were carried out monthly (from winter until summer). The samples were filtered and pre-concentrated/extracted using solid phase extraction (SPE). The pharmaceuticals screening procedure required the construction of two databases, one for each ionization mode (pos. and neg.), which contained information that allowed the identification of the presence of these pharmaceuticals in the studied samples. Com. pharmaceutical compounds were used as anal. standards Based on this strategy and, using liquid chromatog. coupled to high resolution mass spectrometry, it was possible to screen 110 pharmaceuticals and, from these, to confirm the presence of 38 pharmaceuticals in analyzed samples. These results indicate the analytes that should be taken into account in the further development of quant. methods for pharmaceutical anal. In the experiment, the researchers used many compounds, for example, 2-(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid (cas: 41340-25-4Formula: C17H21NO3).

2-(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetic acid (cas: 41340-25-4) belongs to tetrahydropyran derivatives. Dihydropyrans and tetrahydropyrans are examples of cyclic ethers widespread in nature. 2-(Arylmethylene)cyclopropylcarbinols could be converted to the corresponding tetrahydropyrans stereoselectively in the presence of Brønsted acids under mild conditions. A plausible Prins-type reaction mechanism has been proposed.Formula: C17H21NO3

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

The conformational behavior of 2-aryloxytetrahydropyrans and 2-acetoxytetrahydropyran, and barrier to ring inversion was written by Ouedraogo, Adama;Lessard, Jean. And the article was included in Canadian Journal of Chemistry in 1991.Electric Literature of C6H12O2 This article mentions the following:

The ¹³C NMR data of a series of 2-(4-substituted phenoxy)tetrahydropyrans at 156 K and in CF₂Br₂ and CHFCl₂ solvents show that the axial preference increases with electron withdrawal in the aryloxy group: from 79% (ΔG°_E→A = -0.4 kcal mol^-1) (4-OCH₃) to 90% (ΔG°_E→A = -0.7 kcal mol^-1) (4-NO₂) in CF₂Br₂. The axial preference (anomeric effect) is smaller in the more polar CHFCl₂ solvent, as expected, and the substituent effect is smaller also: change in ΔG°_E→A from -0.3 (4-OCH₃) to -0.5 (4-NO₂) kcal mol^-1. However, the axial preference of 2-acetoxytetrahydropyran is shown to be smaller than that of 2-phenoxytetrahydropyran in CF₂Br₂ solvent although the acetoxy group is expected to be more electroneg. than the phenoxy group. Furthermore, the polarity of the solvent has no effect on the conformational equilibrium of 2-acetoxytetrahydropyran. The results are interpreted in terms of both orbital and electrostatic interactions. The ring-inversion barrier of 2-alkoxy- and 2-aryloxytetrahydropyrans, determined by the temperature-coalescence method, is lower than that of tetrahydropyran by about 1.5 kcal mol^-1. In the experiment, the researchers used many compounds, for example, 2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4Electric Literature of C6H12O2).

2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4) belongs to tetrahydropyran derivatives. In organic synthesis, the 2-tetrahydropyranyl group is used as a protecting group for alcohols. The Prins reaction of homoallylic alcohols with aldehydes afforded an alternative method for the preparation of tetrahydropyrans.Electric Literature of C6H12O2

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Sensing or No Sensing: Can the Anomeric Effect Be Probed by a Sensing Molecule? was written by Wang, Chang-Wei;Ying, Fu-Ming;Wu, Wei;Mo, Yi-Rong. And the article was included in Journal of the American Chemical Society in 2011.Recommanded Product: 6581-66-4 This article mentions the following:

The anomeric effect plays a central role in carbohydrate chem., but its origin is controversial, and both the hyperconjugation model and the electrostatic model have been proposed to explain this phenomenon. Recently, Cocinero et al. designed a peptide sensor, which can bind to a sugar mol. Me D-galactose, and claimed that the anomeric effect can be sensed by the spectral changes from the β- to the α-complex, which are ultimately attributed to the lone pair electron d. change on the endocyclic oxygen atom. Here, we provide strong computational evidence showing that the observed spectral changes simply come from the conformational differences between the α- and β-anomers, as the replacement of the endocyclic oxygen atom with a methylene group, which disables both the endo- and the exo-anomeric effects in Me D-galactose, leads to similar spectral shifts. In other words, the “sensor” cannot probe the anomeric effect as claimed. We further conducted detailed energetic and structural analyses to support our arguments. In the experiment, the researchers used many compounds, for example, 2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4Recommanded Product: 6581-66-4).

2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4) belongs to tetrahydropyran derivatives. Tetrahydropyran is a useful synthetic intermediate. Tetrahydropyranyl (THP-) ethers derived from the reaction of alcohols and dihydropyran are common intermediates in organic synthesis. Pyran derivatives such as pyran flavonoids are biologically important. Monosaccharides containing six-membered rings are called pyranose.Recommanded Product: 6581-66-4

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

A facile method for Rh-catalyzed decarbonylative ortho-C-H alkylation of (hetero)arenes with alkyl carboxylic acids was written by Tian, Yiqiang;Liu, Xiaojie;He, Bangyue;Ren, Yuxi;Su, Weiping. And the article was included in RSC Advances in 2021.Formula: C6H10O3 This article mentions the following:

A facile and effective method for Rh-catalyzed direct ortho-alkylation of C-H bonds in (hetero)arenes I (R = 2-methylphenyl, naphthalen-1-yl, thiophen-2-yl, etc.) with com. available carboxylic acids R¹COOH (R¹ = Et, cyclopentyl, 2-(4-bromophenyl)ethyl, etc.) has been developed. This strategy was initiated by in situ conversion of carboxylic acids to anhydrides which, without isolation, underwent Rh-catalyzed direct decarbonylative cross-coupling of aryl carboxamides containing 8-aminoquinoline I (R = 2,6-diethylphenyl, 2-cyclopentyl-6-methylphenyl, 2-methyl-6-phenylphenyl, etc.). The reaction proceeds with high regioselectivity and exhibits a broad substrate scope as well as functional group tolerance. In the experiment, the researchers used many compounds, for example, Tetrahydropyran-4-yl-carboxylic acid (cas: 5337-03-1Formula: C6H10O3).

Tetrahydropyran-4-yl-carboxylic acid (cas: 5337-03-1) belongs to tetrahydropyran derivatives. Tetrahydropyrans and furans principally constitute as a central motif in diverse medicinally privileged molecules. The Prins reaction of homoallylic alcohols with aldehydes afforded an alternative method for the preparation of tetrahydropyrans.Formula: C6H10O3

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio) was written by Perumal, Sasidharan;Gopal Samy, Madhana V.;Subramanian, Dharaneedharan. And the article was included in Journal of Biochemical and Molecular Toxicology in 2021.Synthetic Route of C16H22O10 This article mentions the following:

A secoiridoid glycoside called swertiamarin has been widely used as a herbal medicine for many decades. In particular, swertiamarin from the Enicostema axillare herb has been used as a multipurpose drug to treat innumerable health problems. As this medicine is consumed orally, its toxicity level should be determined To examine the safety of this compound, toxicol. work was done in zebrafish, and this is the first report to describe swertiamarin toxicity in zebrafish. Zebrafish embryos were used in this swertiamarin toxicity study, and morphol. changes were observed Further, the compound was also studied in adult zebrafish to determine the impact of the compound on the fish liver. Enzyme profiling with superoxide dismutase, glutathione peroxidase, catalase, reduced glutathione levels, glutathione S-transferase, lactate dehydrogenase, glutamic oxaloacetic transaminases, lipid peroxidation, Na⁺/K⁺-ATPase, and glutamic pyruvic transaminases was evaluated (p ≤ 0.05). Results suggest that swertiamarin is a safe drug only at a low concentration (40μM). This study also shows that even herbal medicinal compounds may be toxic to humans at higher dosages. Hence, irresp. of whether a drug is synthetic or natural, it needs to be tested for its toxicity before use in humans. In the experiment, the researchers used many compounds, for example, (4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5Synthetic Route of C16H22O10).

(4aR,5R,6S)-4a-Hydroxy-6-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-5-vinyl-4,4a,5,6-tetrahydropyrano[3,4-c]pyran-1(3H)-one (cas: 17388-39-5) belongs to tetrahydropyran derivatives. Dihydropyrans and tetrahydropyrans are examples of cyclic ethers widespread in nature. The bismuth chloride-assisted cross-cyclization between homoallylic alcohols and epoxides provided various benzyl tetrahydropyran derivatives. The reaction afforded good yields of desired products and occurred under mild conditions.Synthetic Route of C16H22O10

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics

Ferrous methanesulfonate as an efficient and recyclable catalyst for the tetrahydropyranylation of alcohols and phenols under solvent-free conditions was written by Wang, Min;Song, Zhiguo;Wan, Xin;Zhao, Shuang. And the article was included in RSC Advances in 2011.Application of 6581-66-4 This article mentions the following:

The synthesis of the target compounds was achieved by a ferrous methanesulfonate-catalyzed tetrahydropyranylation of alcs. (benzylic, primary, isomeric alcs., tertiary, cyclic, allyl and furyl) and phenols at room temperature under solvent-free conditions (green chem. method). The catalytic activity of sixteen metal methanesulfonates was compared under the same conditions, ferrous methanesulfonate proved to be the best. It can be recovered easily and reused for several times without distinct deterioration in catalytic activity. During a competitive protection of the hydroxyl groups between an alc. and a phenol, tetrahydropyranyl ether formed exclusively with the alc. A possible catalytic mechanism was proposed. In the experiment, the researchers used many compounds, for example, 2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4Application of 6581-66-4).

2-Methoxytetrahydro-2H-pyran (cas: 6581-66-4) belongs to tetrahydropyran derivatives. Tetrahydropyran is an important raw material and intermediate used in Organic Synthesis, Pharmaceuticals, Agrochemicals and dyestuff. One classic procedure for the organic synthesis of tetrahydropyran is by hydrogenation of the 3,4-isomer of dihydropyran with Raney nickel.Application of 6581-66-4

Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics