Protection Of Hydroxyl Groups Research Articles

Oxidation of Eugenol Derivatives with KMnO4 and CrO3

AbstractThis study aims to delineate the synthesis of eugenol derivatives, starting with hydroxyl group protection and then the subsequent oxidation stages. Initially, eugenol underwent conversion into acetyleugenol and benzyleugenol during the protection phase. Subsequently, a kinetic oxidation of acetyleugenol with KMnO4 via GC-MS analysis resulted in the identification of four compounds. The kinetic investigation indicated the primary formation of diolacetyleugenol, succeeded by aldehyde eugenol, which further gets converted into its respective carboxylic acid. Additionally, acetyleugenol and benzyleugenol underwent oxidation with CrO3, yielding the corresponding carboxylic acids.

Microwave-Assisted Synthesis of β-N-Aryl Glycoamphiphiles with Diverse Supramolecular Assemblies and Lectin Accessibility.

Glycoamphiphiles have attracted considerable interest in a broad range of application fields owing to their solution and bulk-state self-assembly abilities. Despite their importance, the straightforward synthesis of glycoamphiphiles consisting of a hydrophilic carbohydrate linked to a hydrophobic aglycone remains one of the major challenges in glycosciences. Here, a rapid, simple, and efficient synthetic access to chemically stable glycoamphiphiles at physiological pH, namely, N-(β-d-glycosyl)-2-alkylbenzamide, is reported. It leverages the nonreductive amination of unprotected carbohydrates with ortho-substituted aniline derivatives which could be readily obtained by reacting commercially available primary alkylamines with isatoic anhydride. This strategy avoids protection and deprotection of sugar hydroxyl groups and the use of reductive agents, which makes it advantageous in terms of atom and step economy. Moreover, in order to circumvent the cons of classical N-aryl glycosylation, we investigate the use of microwave as a heat source that provides fast, clean, and high-yield β-N-arylation of unprotected carbohydrates. Their self-assembly into water led to multiple morphologies of dynamic supramolecular glycoamphiphiles that were characterized to assess their ability to bind to lectins from pathogenic bacteria. Biophysical interactions probed by isothermal titration microcalorimetry revealed micromolar affinities for most of the synthesized glycoamphiphiles.

Ultrasound-assisted nucleation and growth of hydroxyl-protected and ligand-free Cs3Cu2X5 nanocrystals with bright luminescence.

The commercial applications of lead halide perovskites are hindered by their negative environmental impact and inherent instability. Consequently, developing environmentally friendly copper-based perovskite materials is crucial for future solid-state lighting and display applications. In this study, an ultrafast high-power ultrasonic synthesis strategy was utilized to achieve uniform nucleation and growth of Cs3Cu2X5 (X = Cl, Br, I) nanocrystals (NCs) that possess remarkable luminescence properties, hydroxyl protection, and ligand-free characteristics. These Cs3Cu2X5 NCs exhibited a tunable spectral range spanning from 446 to 525 nm, accompanied by photoluminescence quantum yields (PLQYs) varying from 0.2% to 79.2%. The spectral attributes of the NCs were effectively controlled by modulating the halide type and composition. It is worth noting that density functional theory (DFT) calculations offer valuable insights into the synthesis of NCs and the selection of suitable alcohol solvents. Moreover, we successfully fabricated an efficient and stable white light-emitting diode (WLED) with a high luminous efficiency of 23 lm W-1 and CIE color coordinates of (0.3266, 0.3487). Our work provides a new strategy to synthesize Cs3Cu2X5 NCs and holds promise for their potential application in display and lighting devices.

Overcoming the structure deficiency of nanodrug coated with tannic acid shell through phenolic hydroxyl protection strategy for Alzheimer's disease combination treatment

Tannic acid (TA) shell is of great interest for nanodrug design due to its versatile application such as antioxidant, antibacterial, anti-inflammatory. However, evidence is emerging that TA air oxidation in storage stage and unfavorable interactions of TA with electrolyte or protein in drug delivery could bring great challenge for the structure stability of nanodrug. In this study, a smart TA shell of nanomicelles was constructed through phenolic hydroxyl protection strategy, and the antioxidant capacity of nanomicelles maintain stable after 24 days storage. The phenolic hydroxyl protective tannic acid micelles (PHPTA micelles) show excellent performance for combination delivery of azoramide (Azo), dantrolene (Dan), Trazodone (Tra) in accelerated senescence (SAMP8) mice. This study may pave the way for the fabrication of nanodrugs with stable and smart TA shell for oxidative stress relevant diseases.

Iron-catalyzed oxidative etherification of benzylic C(sp3)–H bonds with phenols

The first oxidative etherification of benzylic C(sp3)–H bonds with phenols is achieved by using readily available ionic Fe(III) complex [HIPym][FeBr4] as catalyst and DTBP as oxidant. The present work provides a general protocol with high levels of step- and atom-economy for the synthesis of aryl ethers, particularly for aryl benzyl ethers. The direct use of toluene and phenols as starting materials also renders this protocol as a novel strategy for the protection of hydroxyl groups presented in various phenols.

Organic–Inorganic Polyimides with POSS Cages in the Main Chains: An Impact of POSS R Groups on Morphologies and Properties

Two well-defined POSS diamines were synthesized with phenyl (Ph) and iso-butyl (i-Bu) POSS trisilanols as the starting compounds. This approach involves the protection and deprotection of silanol hydroxyl groups with phenylboronic acid and pinacol, followed by the silylation of silanol hydroxyl groups with mono- and dichlorosilanes. With this route of synthesis, two well-defined divinyl POSS macromers were obtained, as evidenced by 1H, 29Si NMR, and mass spectroscopy. These two divinyl POSS macromers were further functionalized into well-defined POSS diamines via the Heck reaction with p-bromoaniline. The successful synthesis of POSS diamines enabled the synthesis of organic–inorganic polyimides with the POSS cages in the main chains. More importantly, the syntheses of these two POSS diamines allowed the examination of the effect of POSS R groups (i.e., Ph and i-Bu) on the morphologies and thermomechanical and dielectric properties of organic–inorganic polyimides. Notably, the types of POSS R groups exerted a profound impact on the morphologies and properties of the organic–inorganic polyimides.

Metallacarborane Synthons for Molecular Construction-Oligofunctionalization of Cobalt Bis(1,2-dicarbollide) on Boron and Carbon Atoms with Extendable Ligands.

The exploitation of metallacarboranes' potential in various fields of research and practical applications requires the availability of convenient and versatile methods for their functionalization with various functional moieties and/or linkers of different types and lengths. Herein, we report a study on cobalt bis(1,2-dicarbollide) functionalization at 8,8'-boron atoms with different hetero-bifunctional moieties possessing a protected hydroxyl function allowing further modification after deprotection. Moreover, an approach to the synthesis of three and four functionalized metallacarboranes, at boron and carbon atoms simultaneously via additional functionalization at carbon to obtain derivatives carrying three or four rationally oriented and distinct reactive surfaces, is described.

Unprecedented neighboring group participation of C2 N-imidoxy functionalities for 1,2-trans-selective glycosylation

Stereoselective glycosylation reactions are important in carbohydrate chemistry. The most used method for 1,2-trans(β)-selective glycosylation involves the neighboring group participation (NGP) of the 2-O-acyl protecting group; nevertheless, an alternative stereoselective method independent of classical NGP would contribute to carbohydrate chemistry, despite being challenging to achieve. Herein, a β-selective glycosylation reaction employing unprecedented NGP of the C2 N-succinimidoxy and phthalimidoxy functionalities is reported. The C2 functionalities provided the glycosylated products in high yields with β-selectivity. The participation of the functionalities from the α face of the glycosyl oxocarbenium ions gives stable six-membered intermediates and is supported by density functional theory calculations. The applicability of the phthalimidoxy functionality for hydroxyl protection is also demonstrated. This work expands the scope of functionalities tolerated in carbohydrate chemistry to include O–N moieties.

Regioselective 2,7-dimethyl-9-phenyl xanthen-9-yl protection and deprotection of nucleosides under mild conditions

A simple and efficient protocol is developed for regioselective protection of primary hydroxyl group of nucleosides using 2,7-dimethylpixyliumtrifluoroacetate, prepared in-situ from 2,7-dimethyl-9-phenylxanthen-9-ol (DMPx-OH) and trifluoroacetic anhydride (TFAA). Furthermore deprotection of DMPx group is accomplished with TFAA in shorter reaction times with excellent yields in DCM:Methanol solvent system. Both procedures are successfully implemented on gram scale for synthesis of natural as well as other modified nucleosides. Various functional groups such as benzoyl, benzyl, tetrahydropyranyl, TBDPS, and formamidine groups are intact during protection with DMPx-group.

Synthesis and Cytotoxic Effects of 3,6‐Bis‐indolyl 2,5‐Dihydroxybenzoquinone Acetates

The synthesis of a novel series of indolyl-2,5-dihydroxybenzoquinone derivatives, analogues of asterriquinones, is reported together with their antiproliferative activity against various carcinoma cell lines, such as A549, MCF7, Hcc827 and PC3. For the synthesis, acid catalyzed reactions of 2,5-diacetoxybenzoquinone with 2-methyl and 1,2-dimethyl indole have been employed. Ten compounds have been tested and exhibited differential activity across the various cell lines. Derivative 7 b was the most cytotoxic with an IC50 value of 25±2.0 μΜ against A549 cancer cells and was more active than cisplatin in PC3 cells (IC50 value of 38±1.5 μΜ). The activity and selectivity of the tested compounds depends both on the number of indole units, the presence of protected hydroxyl groups on 1,4-benzoquinone and N−Me groups on indole.

Advances in Research at Synthesis Process Optimization and Quality Standard Improvement of O-desmethylvenlafaxine Succinate.

We herein describe an optimal approach for the efficient synthesis of O-desmethylvenlafaxine succinate monohydrate (DVS) with high yield and high purity through 5-step reactions, including benzyl protection of the phenolic hydroxyl group, cyclohexanone condensation, deprotection, cyano reduction, dimethylation, and succinic acid salt formation from p-hydroxybenzene acetonitrile as a starting material. 4-Benzyloxyphenylacetonitrile (Intermediate I) was prepared by the hydroxyl protection of the bromide benzyl-p-hydroxyphenylacetonitrile catalyzed by potassium carbonate with 99.83% purity and 98.92% yields. The 1, 2-nucleophilic addition of intermediate I to cyclohexanone promoted by sodium hydroxide with the homogeneous catalyst (n-Bu)4N+Br− to the preparation of 1-[Cyano(4-benzyloxyphenyl)methyl]cyclohexanol (Intermediate II) was obtained by 99.13% purity and 99.71% yields. Cyclohexanone residues and benzyl bromide residues were trace, and tetrabutylammonium bromide residues were UNDER 0.7 ppm, which further improves the residual standards for genotoxic impurities (GIs). 1-[2-amino-1-(4-hydroxyphenyl)ethyl]cyclohexanol hydrochloride (Intermediate III) was prepared by 10% palladium-carbon under 2.0 MPa up to 98.32% purity and 94.20% yields. O-desmethylvenlafaxine (ODV) was synthesized by dimethylation of intermediate III with 37% formaldehyde solution and 85% formic acid solution. The highest purity was up to 99.20% and the yield was up to 84.77%. O-desmethylvenlafaxine succinate monohydrate (DVS) was formed from succinic acid and O-desmethylvenlafaxine (ODV) and crystallized in a mixed solvent of acetone and water (3:1) to obtain 99.92% purity and 90.27% yields. The 5-step total yields of desvenlafaxine succinate monohydrate is 71.09%, and its crystal form has characteristic peaks at 5, 10, 21, and 26 min by XRD powder diffraction, which is consistent with the crystalline form I. Compared with conventional synthesis strategy, we revealed a novel and green process with a high total yield, high atomic economy, low environmental pollution, high operational safety, and high residual standards for genotoxic impurities (GIs), which improves drug safety.

A convenient synthesis of gold nanoparticles in Spirulina extract for rapid visual detection of dopamine in human urine

To visually detect dopamine (DA) in real urine, the sensor responds to changes in wavelength and color was devised. A simple and green method to prepare gold nanoparticles (AuNPs) from Spirulina extract was presented. The weak protection of the alcoholic hydroxyl and carboxyl group of Spirulina polysaccharide/protein on S-AuNPs (AuNPs are prepared with Spirulina extract) were easily replaced by amino and phenolic hydroxyl groups in DA. As a result, the S-AuNPs began to agglomerate, and the color and plasmon resonance absorption peak of the S-AuNPs sol were changed at the same time. DA can be detected as low as 0.21 μM by UV–vis spectroscopy and observed by the naked eye (>5 μM). UV–vis analysis showed that the absorbance ratio (A696/A520) was linear to DA concentration (R2 = 0.99) in the range of 5–40 μM. This method has been applied to detecting DA in human urine samples, and the recovery rate ranged from 101.8% to 102.7%.

Efficient Greener Visible‐Light‐Catalyzed Debenzylation of Benzyl Ethers and Esters: A Gateway to Wider Exploitation of Stable Benzyl Protecting Groups

AbstractA non‐hydrogenolytic mild deprotection strategy for stable benzyl protection of hydroxyl group is one of the long‐cherished goals in multistep synthesis involving carbohydrates or compounds with multiple hydroxyl groups. A greener organo‐photocatalytic method has been developed for mild and efficient visible light catalytic deprotection of benzyl group from benzyl ether and benzyl ester. The newly developed method in ambient condition with only 1 mol% of catalyst loading can efficiently remove highly stable benzyl protection from ethers and esters of wide substrate scope with excellent functional group tolerance, thus proved to be suitable for final stage deprotection. Employment of molecular oxygen as terminal oxidant and excellent yield in the multigram scale reaction signifies the eco‐friendliness, robustness and industrial applicability of the method.

Research progress on hydroxyl protection of iridoid glycosides

Iridoids, an important active ingredient, are widely distributed in varieties of Chinese herbal medicines and have varieties of pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and so on, most of which exist in the form of glycosides in nature. However, its clinical application is limited by poor lipid solubility, low bioavailability and short half-life. It is necessary to optimize the structure of iridoids. It is hard to modify the hydroxyl groups at specific sites because iridoid glycosides are polyhydroxy compounds and very complex. In this paper, the words of ‘Iridoid glycosides’ and ‘Hydroxyl protection’ were used as the keywords, more than 200 articles from 1965 to 2021 were obtained from databases, such as CNKI, PubMed, Scifinder and so on. Finally, 60 articles were selected to summarize the hydroxyl protection of iridoid glycosides, which will provide a theoretical basis for their structural modification and stimulate their application potential in the field of drug research and development.

Practical method for hydroxyl-group protection using strontium metal and readily available silyl chlorides.

We have found that the etherification of silyl-protected secondary alcohols proceeds smoothly in the presence of strontium metal using silyl chloride instead of the expensive, yet more reactive, and commonly used silyl triflate. The reaction occurred almost completely with various alcohols.

Microwave assisted Williamson Ether Synthesis in the absence of Phase Transfer Catalyst

An efficient, economical and eco-friendly microwave assisted protocol for protection of phenolic hydroxyl group is reported. The protocol enables preparation of diphenyl ethers by treatment of various phenols with 2,4-dinitrochlorobenzene in absence of any auxiliary substance such as phase transfer catalyst. This microwave assisted Williamson reaction is more practical and greener way for preparing diphenyl ethers which are useful as agrochemicals.

Electrochemical Dehydrogenative Acetalization Protection of Alcohols with Tetrahydrofuran.

A mild, facile, and environmentally friendly electrochemical protocol for the C(sp3)−H/O−H cross dehydrogenative coupling between various alcohols and tetrahydrofuran with H2 evolution is herein reported. This synthetic strategy does not require external oxidants nor catalysts. The broad functional group compatibility includes hydroxyl, halogens, olefins as well as an alkyne. Initial mechanistic investigations were conducted. The method provides a green and efficient hydroxyl group protection.

Synthesis and characterization of polyurethane–polysiloxane block copolymers modified by α,ω-hydroxyalkyl polysiloxanes with methacrylate side chain

Abstract In order to prepare polyurethane–polysiloxane block copolymers, α,ω-hydroxyalkyl polysiloxanes with methacrylate side chain and α,ω-bis(2-methyl-3-hydroxypropyl)polymethyl(2-methyl-methylpropanoate) siloxanes, were synthesized and characterized in this study. The syntheses process included hydroxyl protection, hydrosilylation, deprotection, and ring-opening equilibrium reactions. The intermediates and target products were characterized by Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance methods. The characterization results showed that each step was successfully carried out in all the cases. Then the waterborne polyurethane–polysiloxane block copolymers were prepared via step-growth polymerization. The properties of the block copolymer films were characterized by thermal gravimetric analysis, differential scanning calorimetry, and dynamic thermomechanical analysis methods in detail. The experimental results showed that the block introduction of hydroxyalkyl polysiloxane could reduce the water absorption of waterborne polyurethane from 62 to 11%, and significantly improve the water resistance of polyurethane. With the introduction of polysiloxane, the tensile strength decreased and the elongation at break increased. At the same time, with the increase of the polysiloxane content, the glass transition temperature of the soft segment decreased to −56.4°C and the thermal decomposition temperature increased to 300°C. The results revealed that the introduction of polysiloxane could effectively improve the comprehensive performance of polyurethane–polysiloxane block copolymer films.

A Simple Synthesis Route for Selectively Methylated β-Cyclodextrin Using a Copper Complex Sandwich Protecting Strategy.

This communication reports a novel synthesis route for the preparation of monofunctionalized β-cyclodextrin in a single stage. The approach involves only the in-situ protection of secondary hydroxyl groups as an excellent alternative to the classical procedure involving a series of five steps of protection and deprotection of hydroxyl groups (both primary and secondary ones) belonging to β-cyclodextrin.

Synthetic Studies toward (−)-Cleistenolide: Highly Stereoselective Synthesis of New γ-Lactone Subunits

This study describes the stereoselective synthesis of two new γ-lactones in 6 and 3 steps and 19 and 32% yield, respectively, directed toward the total synthesis of the natural product (−)-cleistenolide. The starting material was an enantiomerically pure diacetonide diol, derived from d-mannitol with the required stereocenters for (−)-cleistenolide synthesis. γ-Lactone syntheses were based on highly selective protection and deprotection of hydroxyls from d-mannitol. The formation of γ-lactone rings was the culmination of this approach, made possible by a Horner-Wadsworth-Emmons Z-olefination between diacetal aldehyde and ethyl 2-(bis(o-tolyloxy)phosphoryl)acetate to produce an unsaturated ester. The Z-isomer ester was highly favored in relation to the E-isomer (Z/E ratio of 94:6), allowing the formation of the γ-lactone ring under acid catalysis. This strategy precluded the use of chiral auxiliaries or catalysts for the control of stereocenters in the novel γ-lactones.