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Molecules (Basel, Switzerland) May 2024Radical reactions are powerful in the synthesis of diverse molecular scaffolds bearing functional groups. In previous review articles, we have presented... (Review)
Review
Radical reactions are powerful in the synthesis of diverse molecular scaffolds bearing functional groups. In previous review articles, we have presented 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6- and 1,7-difunctionalizations, and addition followed by cyclization reactions. Presented in this paper is radical cyclization followed by the second functionalization reaction. The second functionalization could be realized by atom transfer reactions, radical or transition metal-assisted coupling reactions, and reactions with neutral molecules, cationic and anionic species.
PubMed: 38893437
DOI: 10.3390/molecules29112559 -
IScience Sep 2023An unprecedented efficient protocol is developed for the oxidative cleavage of C≡C bonds in alkynes to produce structure-diverse esters using heterogeneous cobalt...
An unprecedented efficient protocol is developed for the oxidative cleavage of C≡C bonds in alkynes to produce structure-diverse esters using heterogeneous cobalt nanoparticles as catalyst with molecular oxygen as the oxidant. A diverse set of mono- and multisubstituted aromatic and aliphatic alkynes can be effectively cleaved and converted into the corresponding esters. Characterization analysis and control experiments indicate high surface area and pore volume, as well as nanostructured nitrogen-doped graphene-layer coated cobalt nanoparticles are possibly responsible for excellent catalytic activity. Mechanistic studies reveal that ketones derived from alkynes under oxidative conditions are formed as intermediates, which subsequently are converted to esters through a tandem sequential process. The catalyst can be recycled up to five times without significant loss of activity.
PubMed: 37664625
DOI: 10.1016/j.isci.2023.107608 -
Inorganic Chemistry Apr 2024Metathesis reactions, including alkane, alkene, and alkyne metatheses, have their origins in the fundamental understanding of chemical reactions and the development of...
Metathesis reactions, including alkane, alkene, and alkyne metatheses, have their origins in the fundamental understanding of chemical reactions and the development of specialized catalysts. These reactions stand as transformative pillars in organic chemistry, providing efficient rearrangement of carbon-carbon bonds and enabling synthetic access to diverse and complex compounds. Their impact spans industries such as petrochemicals, pharmaceuticals, and materials science. In this work, we present a detailed mechanistic study of the Re(V) catalyzed alkyne metathesis through density functional theory calculations. Our findings are in agreement with the experimental evidence from Jia and co-workers and unveil critical factors governing catalyst performance. Our work not only enhances our understanding of alkyne metathesis but also contributes to the broader landscape of catalytic processes, facilitating the design of more efficient and selective transformations in organic synthesis.
PubMed: 38507560
DOI: 10.1021/acs.inorgchem.3c04235 -
Nature Communications Oct 2023Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via π-ƞ substitution have emerged as a reliable method to construct stereogenic...
Transition metal-catalyzed asymmetric hydrofunctionalizations of unsaturated bonds via π-ƞ substitution have emerged as a reliable method to construct stereogenic centers, and mainly rely on the use of heteroatom-based or carbon nucleophiles bearing acidic C-H bonds. In comparison, sp carbon nucleophiles are generally not under consideration because of enormous challenges in cleaving corresponding inert sp C-H bonds. Here, we report a protocol to achieve asymmetric formal sp hydrocarbonations, including hydroalkenylation, hydroallenylation and hydroketenimination of both 1,3-dienes and alkynes via hydroalkylation and Wittig reaction cascade. A series of unachievable motifs via hydrofunctionalizations, such as di-, tri- and tetra-substituted alkenes, di-, tri- and tetra-substituted allenes, and tri-substituted ketenimines in allyl skeletons are all facilely constructed in high regio-, diastereo- and enantioselectivities with this cascade design. Stereodivergent synthesis of all four stereoisomers of 1,4-diene bearing a stereocenter and Z/E-controllable olefin unit highlights the power of present protocol. An interesting mechanistic feature is revealed that alkyne actually undergoes hydrocarbonation via the formation of conjugated diene intermediate, different from conventional viewpoint that the hydrofunctionalization of alkynes only involves allene species.
PubMed: 37813855
DOI: 10.1038/s41467-023-42160-2 -
Journal of the ASEAN Federation of... 2024This study aimed to evaluate the effects of the combination of curcumin and piperine supplementation on Fasting Plasma Glucose (FPG), Homeostatic Model of Insulin... (Meta-Analysis)
Meta-Analysis Review
Effects of Combination of Curcumin and Piperine Supplementation on Glycemic Profile in Patients with Prediabetes and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.
OBJECTIVE
This study aimed to evaluate the effects of the combination of curcumin and piperine supplementation on Fasting Plasma Glucose (FPG), Homeostatic Model of Insulin Resistance (HOMA-IR), and Body Mass Index (BMI) in patients with prediabetes and type 2 Diabetes Mellitus (T2DM). This review was done to identify potential herbal remedies that may help improve glycemic parameters, leading to better health outcomes in combination with current antidiabetic treatment.
METHODOLOGY
This systematic review was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It was conducted in 2023 with sources and databases from MEDLINE, EBSCO-Host, ScienceDirect and ProQuest. This paper included randomized-controlled trials exploring the effects of the combination of curcumin and piperine on patients with prediabetes and T2DM. Systematic reviews, observational studies, case reports, case series, conference abstracts, book sections, commentaries/editorials, non-human studies and articles with unavailable full-text and written in non-English language, were excluded. The key terms for the literature search were "curcumin," "piperine," "prediabetes" and "Type 2 Diabetes Mellitus." We use Cochrane Risk of Bias (RoB) 2 for quality assessment of the included studies and Review Manager (RevMan) 5.4 to do the meta-analysis.
RESULTS
A total of three studies were included in this systematic review. Two studies from Neta et al., and Cicero et al., showed no significant difference in HOMA-IR, BMI and FPG levels between the curcumin, piperine and placebo groups. One study from Panahi et al. demonstrated a significant difference in BMI levels between the curcumin and piperine and placebo groups ( <0.01). The meta-analysis showed that FPG levels, HOMA-IR and BMI improved among patients with diabetes given in curcumin and piperine with reported mean differences (MD) of = -7.61, 95% CI [-15.26, 0.03], = 0.05, MD = -0.36, 95% CI [-0.77 to 0.05], = 0.09, and MD = -0.41, 95% CI [-0.85 to 0.03], = 0.07, respectively).
CONCLUSIONS
The supplementation of curcumin and piperine showed a numerical reduction in FPG, HOMA-IR and BMI, but were not statistically significant. Further research is needed as there is a paucity of studies included in the review.
Topics: Humans; Alkaloids; Benzodioxoles; Blood Glucose; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Drug Therapy, Combination; Insulin Resistance; Piperidines; Polyunsaturated Alkamides; Prediabetic State
PubMed: 38863920
DOI: 10.15605/jafes.039.01.18 -
Analytical Chemistry Dec 2023Protein properties and interactions have been widely investigated by using external labels. However, the micromolar sensitivity of the current dyes limits their...
Protein properties and interactions have been widely investigated by using external labels. However, the micromolar sensitivity of the current dyes limits their applicability due to the high material consumption and assay cost. In response to this challenge, we synthesized a series of cyanine5 (Cy5) dye-based quencher molecules to develop an external dye technique to probe proteins at the nanomolar protein level in a high-throughput one-step assay format. Several families of Cy5 dye-based quenchers with ring and/or side-chain modifications were designed and synthesized by introducing organic small molecules or peptides. Our results showed that steric hindrance and electrostatic interactions are more important than hydrophobicity in the interaction between the luminescent negatively charged europium-chelate-labeled peptide (Eu-probe) and the quencher molecules. The presence of substituents on the quencher indolenine rings reduces their quenching property, whereas the increased positive charge on the indolenine side chain improved the interaction between the quenchers and the luminescent compound. The designed quencher structures entirely altered the dynamics of the Eu-probe (protein-probe) for studying protein stability and interactions, as we were able to reduce the quencher concentration 100-fold. Moreover, the new quencher molecules allowed us to conduct the experiments using neutral buffer conditions, known as the peptide-probe assay. These improvements enabled us to apply the method in a one-step format for nanomolar protein-ligand interaction and protein profiling studies instead of the previously developed two-step protocol. These improvements provide a faster and simpler method with lower material consumption.
Topics: Coloring Agents; Carbocyanines; Peptides; Luminescence; Fluorescent Dyes
PubMed: 38060502
DOI: 10.1021/acs.analchem.3c02844 -
Organometallics Aug 2023Metalation of -(2,6-dibenzhydryl-4-tolyl)adamantane-1-carboxamide (, Ar*N(H)-C(O)-Ad) with M(NMe) (M = Ti, Zr, Hf) yields amidate complexes Ar*N=C(Ad)-O-Ti(NMe) () as...
Metalation of -(2,6-dibenzhydryl-4-tolyl)adamantane-1-carboxamide (, Ar*N(H)-C(O)-Ad) with M(NMe) (M = Ti, Zr, Hf) yields amidate complexes Ar*N=C(Ad)-O-Ti(NMe) () as well as bis(amidate) compounds (Ar*N=C(Ad)-O)M(NMe) (M = Zr (), Hf ()). In , the amidate ligand acts as a monodentate base via the oxygen atom with the Ti center in a slightly distorted tetrahedral environment. The steric requirement of the amidate ligand stabilizes the small coordination number of four of the Ti atom. In congeners and , two bidentate amidate ligands exist in the coordination spheres, leading to hexacoordinate group IV metal atoms. The small bite angles of the Zr- and Hf-bound amidate ligands lead to severe distortion of the octahedral environments of the Zr and Hf centers. Titanium compound is an unsuitable choice to catalyze hydrofunctionalization of alkynes with amines and phosphane oxides and despite the significantly smaller p value of the carboxylic amide, formation of carboxamide is the dominant reaction upon addition of amines or phosphane oxides to release intramolecular steric strain introduced by the very bulky adamantylamidato ligand.
PubMed: 37654652
DOI: 10.1021/acs.organomet.3c00291 -
Pain Jan 2024N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes... (Observational Study)
Observational Study
N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a "high-level" endocannabinoid group and a "low-level" group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group ( P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies.
Topics: Humans; Chromatography, Liquid; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Neuropathies; Endocannabinoids; Pain; Polyunsaturated Alkamides; Receptors, Cannabinoid; Tandem Mass Spectrometry
PubMed: 37578507
DOI: 10.1097/j.pain.0000000000003015 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2023Several examples of the cyaphide-azide 1,3-dipolar cycloaddition reaction to afford metallo-triazaphospholes are reported. The gold(I) triazaphospholes Au(IDipp)(CPN R)...
Several examples of the cyaphide-azide 1,3-dipolar cycloaddition reaction to afford metallo-triazaphospholes are reported. The gold(I) triazaphospholes Au(IDipp)(CPN R) (IDipp=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; R= Bu, Ad, Dipp), magnesium(II) triazaphospholes, {Mg( NacNac)(CPN R)} ( NacNac=CH{C(CH )N(Dipp)} , Dipp=2,6-diisopropylphenyl; R= Bu, Bn), and germanium(II) triazaphosphole Ge( NacNac)-(CPN Bu) can be prepared straightforwardly, under mild conditions and in good yields, in a manner reminiscent of the classic alkyne-azide click reaction (albeit without a catalyst). This reactivity can be extended to compounds with two azide functional groups such as 1,3-diazidobenzene. It is shown that the resulting metallo-triazaphospholes can be used as precursors to carbon-functionalized species, including protio- and iodo-triazaphospholes.
PubMed: 37338223
DOI: 10.1002/chem.202301648 -
Nature Communications May 2024Phosphanorcaradienes are an appealing class of phosphorus compounds that can serve as synthons of transient phosphinidenes. However, the synthesis of such species is a...
Phosphanorcaradienes are an appealing class of phosphorus compounds that can serve as synthons of transient phosphinidenes. However, the synthesis of such species is a formidable task owing to their intrinsic high reactivity. Herein we report straightforward synthesis, characterization and reactivity studies of a phosphanorcaradiene, in which one of the benzene rings in the flanking fluorenyl substituents is intramolecularly dearomatized through attachment to the phosphorus atom. It is facilely obtained by the reduction of phosphorus(III) dichloride precursor with potassium graphite. Despite being thermally robust, it acts as a synthetic equivalent of a transient phosphinidene. It reacts with trimethylphosphine and isonitrile to yield phosphanylidene-phosphorane and 1-phospha-3-azaallene, respectively. When it is treated with one and two molar equivalents of azide, iminophosphane and bis(imino)phosphane are isolated, respectively. Moreover, it is capable of activating ethylene and alkyne to afford [1 + 2] cycloaddition products, as well as oxidative cleavage of Si-H and N-H bonds to yield secondary phosphines. All the reactions proceed smoothly at room temperature without the presence of transition metals. The driving force for these reactions is most likely the high ring-constraint of the three-membered PC ring and recovery of the aromaticity of the benzene ring.
PubMed: 38811584
DOI: 10.1038/s41467-024-49042-1