6-membered Ring Research Articles

Operando Characterization and Molecular Simulations Reveal the Growth Kinetics of Graphene on Liquid Copper During Chemical Vapor Deposition.

In recent years, liquid metal catalysts have emerged as a compelling choice for the controllable, large-scale, and high-quality synthesis of two-dimensional materials. At present, there is little mechanistic understanding of the intricate catalytic process, though, of its governing factors or what renders it superior to growth at the corresponding solid catalysts. Here, we report on a combined experimental and computational study of the kinetics of graphene growth during chemical vapor deposition on a liquid copper catalyst. By monitoring the growing graphene flakes in real time using in situ radiation-mode optical microscopy, we explore the growth morphology and kinetics over a wide range of CH4-to-H2 pressure ratios and deposition temperatures. Constant growth rates of the flakes' radius indicate a growth mode limited by precursor attachment, whereas methane-flux-dependent flake shapes point to limited precursor availability. Large-scale free energy simulations enabled by an efficient machine-learning moment tensor potential trained to density functional theory data provide quantitative barriers for key atomic-scale growth processes. The wealth of experimental and theoretical data can be consistently combined into a microkinetic model that reveals mixed growth kinetics that, in contrast to the situation at solid Cu, is partly controlled by precursor attachment alongside precursor availability. Key mechanistic aspects that directly point toward the improved graphene quality are a largely suppressed carbon dimer attachment due to the facile incorporation of this precursor species into the liquid surface and a low-barrier ring-opening process that self-heals 5-membered rings resulting from remaining dimer attachments.

Enhancing catalytic activity with less metal resource by regulating zeolite topology

Big-ring topology of zeolite is crucial to the catalytic activity of selective catalytic reduction (SCR) of nitrogen oxide (NOx). More works should explore how to increase the number of the big-ring topology. This work regulated ZSM-5 topologies by different acids and amino acids, exchanged Cu species into the regulated zeolites, and compared their SCR performances. L-aspartate- and L-cysteine-regulated ZSM-5 removed 67 ∼ 73 % of NO (1000 ppm, 15,000 h−1) at 150 °C. Their Cu contents were only 0.04 wt%. Under the same catalytic conditions, citric acid-regulated ZSM-5 only reached a conversion of 19 % with a Cu content of 0.15 wt%. After detailed characterizations, primary 10-membered ring (MR) on (200) plane of ZSM-5 was retained after mild treatment of the amino acids. At the same time, 5-MR on (351) and (352) planes were opened to form more 10-MR. 10-MR along (501) plane was reinforced. As a result, the 10-MR content was increased from 22 % (citric acid) to 32 % (L-aspartate and L-cysteine). The 10-MR-localized Cu was more effective than other species. Above results are in favor of understanding topology-activity relationship in zeolite. Synthesizing a more effective catalyst with less active metal is also helpful to resource saving.

Dual-Channel Imine-Amine Photoisomerization in a Benzoimidazole and Benzothiazole Coupled System: Photophysics and Applications.

A molecule, namely 2-(1H-benzo[d]imidazol-2-yl)-6-(benzo[d]thiazol-2-yl)-4-bromophenol (BIBTB), having a two-way proton transfer unit of thiazole and imidazole moieties was synthesized and characterized by NMR, electrospray ionization mass spectrometry (ESI-MS), and single-crystal diffraction studies. Steady state and time-resolved spectral studies of BIBTB support excited state intramolecular proton transfer (ESIPT), causing imine-amine tautomerization through a two-way 6-membered H-bonded ring, where the N atoms of benzothiazole and the benzoimidazole unit are involved as proton acceptor sites. Interestingly, in a nonpolar and moderately polar solvent, photoisomerization in BIBTB is found to be favored toward the thiazole ring, whereas in a highly polar solvent, it is favored toward the imidazole ring. A spectral comparison of BIBTB with judicially designed molecules 2-(benzo[d]thiazol-2-yl)-4-bromophenol (HBT) and 2-(1H-benzo[d]imidazol-2-yl)-4-bromophenol (BIB) supports these inferences. Theoretical calculation using the Density Functional Theory (DFT) at CAM-B3LYP/6-311+G(d,p) level supports the existence of two low-energy 6-membered hydrogen-bonded planar conformers in the ground state in the gas phase and in solvents of different dielectrics. The potential energy curves (PECs) calculated along the proton transfer (PT) coordinate are found to have a high energy barrier in the ground state and to be barrierless or have a low energy barrier in the excited state for both the forms. The calculated vertical excitation and the emission energy from the relaxed excited and PT states show good correlation with the experimental spectral data. Aggregation of BIBTB in water with red shifted emission was established from X-ray single-crystal structure analysis, solid state emission, and Dynamic Light Scattering (DLS) measurement. The molecule BIBTB also acts as a fluorescence probe for sensing the explosive picric acid in the subnano scale and can be used to determine the proportion of water in dimethyl sulfoxide (DMSO) solvent.

Development of novel pyrimidine nucleoside analogs as potential anticancer agents: Synthesis, characterization, and In-vitro evaluation against pancreatic cancer

The present study proposed modification of 5-FU by conjugation with an acyl chloride and a 5-membered heterocyclic ring to improve its in-vitro cytotoxicity and metabolic stability. XYZ-I-71 and XYZ-I-73 were synthesized by introducing a tetrahydrofuran ring on 5-fluorocytosine (a precursor of 5-FU) and conjugation with octanoyl chloride and lauroyl chloride, respectively. The structure of the synthesized compounds was validated using NMR and micro-elemental analysis. The antiproliferative activity of the analogs was determined against MiaPaCa-2, PANC-1, and BxPC-3 pancreatic cancer cells. The analog's stability in human liver microsomes was quantified by HPLC. We found that the XYZ-I-73 (IC50 3.6 ± 0.4 μM) analog was most effective against MiaPaCa-2 cells compared to XYZ-I-71(IC50 12.3 ± 1.7 μM), GemHCl (IC50 24.2 ± 1.3 μM), Irinotecan (IC50 10.1 ± 1.5 μM) and 5-FU (IC50 13.2 ± 1.1 μM). The antiproliferative effects of this analog in Miapaca-2 cells is evident based on it having a 7-fold,3-fold, and 4-fold increased cytotoxic effect over Gem-HCl, Irinotecan, and 5-FU, respectively. On the other hand, XYZ-I-71 exhibited a 2-fold increased cytotoxic effect over Gem-HCl but a comparable cytotoxic effect to 5-FU and Irinotecan in MiaPaCa-2 cells. A similar trend of higher XYZ-I-73 inhibition was observed in PANC-1 and BxPC-3 cultures. For 48-h MiaPaCa-2 cell migration studies, XYZ-I-73 (5 μM) significantly reduced migration (# of migrated cells, 168 ± 2.9), followed by XYZ-I-71(315±2.1), Gem-HCl (762±3.1) and 5-FU (710 ± 3.2). PARP absorbance studies demonstrated significant inhibition of PARP expression of XYZ-I-73 treated cells compared to 5-FU, GemHCl, and XYZ-I-71. Further, BAX and p53 expressions were significantly increased in cells treated with XYZ-I-73 compared to 5-FU, GemHCl, and XYZ-I-71. In-vitro, metabolic stability studies showed that 80 ± 5.9% of XYZ-I-71 and XYZ-I-73 remained intact after 2 h exposure in liver microsomal solution compared to 5-FU. The XYZ-I-73 analog demonstrated a remarkable cytotoxic effect and improved in-vitro metabolic stability over the selected standard drugs and may have potential anticancer activity against pancreatic cancer.

Total Synthesis of Dragocins A-C through Electrochemical Cyclization.

The first total synthesis of dragocins A-C, remarkable natural products containing an unusual C4' oxidized ribose architecture bridged by a polyhydroxylated pyrrolidine, is presented through a route featuring a number of uncommon maneuvers. Several generations towards the target molecules are presented, including the spectacular failure of a key C-H oxidation on a late-stage intermediate. The final route features rapid, stereocontrolled access to a densely functionalized pyrrolidine and an unprecedented diastereoselective oxidative electrochemical cyclization to forge the hallmark 9-membered ring. Preliminary studies suggest this electrochemical oxidation protocol is generally useful.

Discovery of Novel 11-Membered Templates as Squalene Synthase Inhibitors.

Squalene synthase is one of the most promising pharmaceutical targets to treat hyperlipidemia. Inhibition of the squalene synthase causes a decrease in the hepatic cholesterol concentration. We have already reported the design and synthesis of highly potent benzhydrol-type squalene inhibitors. Although these templates showed unique and potent cyclic active conformations via intramolecular hydrogen bonds, the in vivo cholesterol-lowering efficacy was insufficient. We attempted to improve their potential as an orally active medicine. In our medicinal chemistry effort, cyclized 11-membered ring templates were acquired. The novel series of compounds exhibited potent squalene synthase inhibitory activity, and one of the derivatives, isomer A-(1S, 3R)-14i, showed plasma lipid-lowering efficacy in hamster and marmoset repeated-dose studies. Our findings provide valuable insights into the design and development of novel and unique 11-membered ring-type highly potent squalene synthase inhibitors.

Valuable insights into the structural, electronic, and aromaticity aspects of azulene and its monophospha-derivatives

Azulene-based conjugated systems have garnered considerable interest owing to their atypical structures. The incorporation of a phosphorous atom into the azulene framework offers an enticing prospect for the creation of unique organophosphorous π-conjugated compounds. No such phosphaazulene skeleton however has been reported to date. Here, density functional theory calculations were employed to examine the physicochemical properties and aromaticity of azulene and its monophospha-derivatives. The electronic, magnetic, and structural properties were taken into consideration. The reactivity of azulene and its monophospha-analogs including 1-phospha (1p), 2-phospha (2p), 4-phospha (3p), 5-phospha (4p), and 6-phosphaazulene (5p), was examined through local electrophilicity and local nucleophilicity indices. The stability and aromaticity of these compounds were determined using DFT calculations with the B3LYP/6–311 + G(d,p) method. The stability of monophosphaazulene derivatives is significantly influenced by the position of the phosphorus atom, as indicated by the energy calculations. The order of stability was found to be 1p > 2p > 5p > 3p > 4p. Aromaticity studies based on HOMA, ΔBl, FLUπ, SA, and NICS indices indicated that the incorporation of a phosphorus atom into the 5-membered ring decreased its aromaticity while simultaneously increasing the aromaticity of the 7-membered ring. However, replacing the carbon atom with phosphorus atom in the 7-membered ring reduced the aromaticity of both rings. Additionally, the ability of π-stacking, as determined by the LOLIPOP criterion, was reduced in the monophosphaazulene derivatives compared to azulene, except for compound 5p. The order of π-stacking ability was 5p > azulene > 2p > 1p > 4p > 3p. Overall, there was a good agreement between the various aromaticity indices, providing consistent results for both rings in azulene and monophosphaazulenes.

Revving up a Designed Copper Nitrite Reductase Using Non-Coded Active Site Ligands.

Herein, we report a three stranded coiled-coil (3SCC) de novo protein containing a type II copper center (CuT2) composed of 6-membered ring N-heterocycles. This design yields the most active homogenous copper nitrite reductase (CuNiR) mimic in water. We achieved this result by controlling three factors. First, previous studies with Nδ and Nε -Methyl Histidine had indicated that a ligand providing pyridine-like electronic character to the copper site was superior to the more donating Nδ for nitrite reduction. By substitution of the parent histidine with the non-coded amino acids pyridyl alanine (3'-Pyridine [3'Py] vs 4'-Pyridine [4'Py]), an authentic pyridine donor was employed without the complications of the coupling of both electronic and tautomeric effects of histidine or methylated histidine. Second, by changing the position of the nitrogen atom within the active site (4'-Pyridine vs. 3'Pyridine) a doubling of the enzyme's catalytic efficiency resulted. This effect was driven exclusivity by substrate binding to the copper site. Third, we replaced the leucine layer adjacent to the active site with an alanine, and the disparity between the 3'Py and 4'Py became more apparent. The decreased steric bulk minimally impacted the 3'Py derivative; however, the 4'Py K m decreased by an order of magnitude (600 mM to 50 mM), resulting in a 40-fold enhancement in the k cat/K m compared to the analogues histidine site and a 1500-fold improvement compared with the initially reported CuNiR catalyst of this family, TRIW-H. When combined with XANES/EXAFS data, the relaxing of the Cu(I) site to a more 2-coordinate Cu(I) like structure in the resting state increases the overall catalytic efficiency of nitrite reduction via the lowering of K m. This study illustrates how by combining advanced spectroscopic methods, detailed kinetic analysis, and a broad toolbox of amino acid side chain functionality, one can rationally design systems that optimize biomimetic catalysis.

Single crystal polarization-orientation Raman spectroscopy of zeolite LTA with confined S3− anions - High dielectric constant nanoporous material

We apply polarization-orientation Raman spectroscopy, as an alternative to X-ray diffraction, to LTA single crystals containing S3− in sodalite cages additionally to S8 rings in large cavities. The sample was obtained via sulfur vapor adsorption at ∼550 °C (LTA-S-550). We show that S3− is located in the (110) plane with its 2-fold axis along the LTA 4-fold axis. The anion position suggests strong interaction of its terminal atoms with Na+ localized in LTA 6-membered rings. The anions display optical absorption band at ∼590 nm (2.1 eV) and resonant Raman enhancement. We observe a record-high S3− bond-bending mode frequency ∼274 cm−1 due to a strong bond-angle contraction. This leads to the Fermi resonance of its overtone with the symmetric bond-stretching mode in the frequency range of 544–552 cm−1. An anomalous Raman downshift of the S3− bond-stretching modes with a decrease of temperature is observed and attributed to partial compressive stress relaxation. Luminescence band at ∼845 nm is observed suggesting considering LTA-S-550 as an interesting light-emitting material. We discuss a role of S3− in the high dielectric constant up to ∼160 and a possible contribution of the anion to the ion-exchange selectivity to Sr2+/Cs+ enhancements of LTA with sulfur.

Expected values of sum-based topological indices of random cyclodecane chains

Cyclodecanes, belonging to the class of aliphatic cycloalkanes, comprise non-aromatic carbon-atom rings. Within the 10-membered ring, cyclodecanes exhibit various isomers, characterized by different spatial arrangements of carbon atoms. Serving as model compounds in organic studies, cyclodecanes offer insights into the properties and reactivity of cyclic hydrocarbons. The chemistry of cyclodecane serves as a valuable foundation for understanding the behavior of more complex hydrocarbons. In this paper, we explore the potential probabilities of random cyclodecane chains Dtρ of length t ≥ 3. We derive exact expressions for the expected values of the modified second Zagreb index, inverse index, and second NDe index. A theoretical comparative analysis of these descriptors is provided, accompanied by graphical and numerical representations of the obtained results.

Hierarchical beta zeolites assisted aromatics production from lignin via catalytic fast pyrolysis

Converting lignin waste into aromatics is a challenging but crucial aspect of lignin valorization. Although ZSM-5 zeolite is extensively used in lignin deoxygenation, its 10-membered ring (MR) channels limit the diffusion of bulky phenols and tend to produce coke. Herein, a series of 12-MR beta zeolites with varying acidity and hierarchical porosity were synthesized for lignin catalytic fast pyrolysis (CFP). An optimal lignin pyrolysis temperature of 600 °C was initially selected. Subsequently, lignin CFP demonstrated that beta zeolite with medium acidity facilitated aromatics production, with Beta(36) even outperforming ZSM-5(36). The introduction of mesopores further enhanced lignin deoxygenation and the hierarchical B36-0.3-24 increased aromatics selectivity to 56.0 area%, which was 1.5 times that of Beta(36). Combined with the CFP of model compounds (vanillin and catechol), it was inferred that the mesopores and weak acidity played a key role in heavy phenols conversion and aromatics production. In addition, B36-0.3-24 exhibited outstanding reusability in pyrolysis regeneration cycles, underscoring its potential for practical application in lignin valorization.

Exploring engineering strategies that enhance de novo production of exotic cyclopropane fatty acids in Saccharomyces cerevisiae.

Cycloalkanes have broad applications as specialty fuels, lubricants, and pharmaceuticals but are not currently available from renewable sources, whereas, production of microbial cycloalkanes such as cyclopropane fatty acids (CFA) has bottlenecks. Here, a systematic investigation was undertaken into the biosynthesis of CFA in Saccharomyces cerevisiae heterologously expressing bacterial CFA synthase. The enzyme catalyzes formation of a 3-membered ring in unsaturated fatty acids. Monounsaturated fatty acids in phospholipids (PL) are the site of CFA synthesis; precursor cis-Δ9 C16 and C18 fatty acids were enhanced through OLE1 and SAM2 overexpression which enhanced CFA in PL. CFA turnover from PL to storage in triacylglycerols (TAG) was achieved by phospholipase PBL2 overexpression and acyl-CoA synthase to increase flux to TAG. Consequently, CFA storage as TAG reached 12mgg-1 DCW, improved 3-fold over the base strain and >22% of TAG was CFA. Our research improves understanding of cycloalkane biosynthesis in yeast and offers insights into processing of other exotic fatty acids.

Accessing Medium-Sized Rings via Vinyl Carbocation Intermediates.

Medium-sized rings (8-11-membered cycles) are often more challenging to synthesize than smaller rings (5-7-membered cycles) due to ring strain. Herein, we report a catalytic method for forming 8- and 9-membered rings that proceeds via the intramolecular Friedel-Crafts reactions of vinyl carbocation intermediates. These reactive species are generated catalytically through the ionization of vinyl toluenesulfonates by a Lewis acidic lithium cation-weakly coordinating anion salt.

Synthesis and properties of doubly diphenylene-fused benzopyrrolo[1,4]diazocine with a [7-8-7] successive ring-fused structure

Abstract We explored a π-electronic system with a successively fused [7-8-7]-membered ring structure. X-ray analysis revealed its nonplanar structure with a mean plane deviation (MPD) of 1.53 Å. Compared with a reference compound with a [7-6-7]-membered ring structure (MPD: 0.38 Å), the incorporation of an 8-membered ring induced larger nonplanarity. On the other hand, replacing the 6-membered ring with an 8-membered ring induced a smaller strain in energy, as suggested by using DFT calculations. The π-orbital axis vector analysis showed that the nonplanarity was mainly dictated by torsion, not pyramidalization.

The interpretation of diverging hydrogen and carbon dioxide permeations with temperature across silica-based membranes

Hydrogen (H2) permeance across silica-based membranes increases with temperature, but carbon dioxide (CO2) permeance decreases. Because of the opposite signs of activation energies for H2 and CO2 permeation, silica-based membranes are widely used in separating H2 and CO2 at high temperatures due to the elevated difference between H2 and CO2 permeabilities. However, there has not been an explanation of the diverging permeance between H2 and CO2 with temperature. This study developed a gas permeation model encompassing gas penetration through silica matrix, Knudsen diffusion, and viscous flow. An Oscillator model with an effective medium approach was used to screen all possible pore size distributions and calculate the gas penetration through the silica matrix. However, no pore size distribution could allow positive activation energy for hydrogen and negative activation energy for carbon dioxide at the same time. After including Knudsen diffusion and viscous flow, the diverging permeance between H2 and CO2 with temperature was successfully interpreted. The pore size distribution and the fractional contribution from Knudsen diffusion and viscous flow, which could best fit experimental activation energies for H2 and CO2 permeation, were identified. In the silica matrix that formed the membranes, 5-membered rings were the dominant structures in pores, which was responsible for the positive apparent activation energy for H2. The negative CO2 apparent activation energy indicated that it was inevitable to have some Knudsen diffusion and viscous flow through some imperfections of the membrane. Our model demonstrated the importance of high-temperature gas separation, as high temperature could minimize the undesirable gas flow through imperfections. This study also implied that further improvement of H2/CO2 separation by silica-based membranes could be achieved by reducing imperfections.

Total Synthesis of Isoxeniolide A.

Isoxeniolide A is a highly strained xenicane diterpenoid of marine origin. This natural product is representative for a subfamily of xenicanes incorporating an allylic hydroxy group in the nine-membered ring; members of this xenicane subfamily so far have not been targeted by total synthesis. Herein, we describe the first asymmetric total synthesis of isoxeniolide A. Key to forming the challenging E-configured cyclononene ring was a diastereoselective intramolecular Nozaki-Hiyama-Kishi reaction. Other important transformations include an enzymatic desymmetrization for absolute stereocontrol, a diastereoselective cuprate addition and the use of a bifunctional vinyl silane building block. Our strategy also permits access to the enantiomer of the natural product and holds potential to access a multitude of xenicane natural products and analogs for structure-activity relationship studies.

Organocatalytic Enantioselective Synthesis of Seven-Membered Ring with Inherent Chirality.

Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).

Enantioselective Total Synthesis of (-)-Vinigrol: The Evolution of a Transannular Diels-Alder Strategy.

Vinigrol is a structurally and stereochemically complex diterpenoid that displays various potent pharmacological activities. Two generations of synthetic routes were designed and pursued based on a transannular Diels-Alder (TADA) cycloaddition strategy. An intramolecular [2 + 2]photocycloaddition in the presence of the chelating Lewis acid (MgBr2·Et2O) was first discovered to enable the reaction of sterically challenging substrates, which was followed by [2 + 2]cycloreversion to provide α-pyrones fused with a 10-membered ring. Eventually, a new and scalable synthetic route toward (-)-vinigrol was developed and provided over 600 mg materials, manifesting the power of macrocyclic stereocontrol and TADA reaction.

Biological Activities of Aurones: A Brief Summary

Abstract: Aurones are structural isomers of flavones and flavonols with the basic C6–C3–C6 skeleton arranged as (Z)-2-benzylidenebenzofuran-3(2H)-one, which contain an exocyclic carbon-carbon double bond bridging the benzofuranone and phenyl rings. In aurone, a chalcone-like group is closed into a 5-membered ring instead of the 6-membered ring more typical of flavonoids, which forms the core for a family of derivatives that are known collectively as aurones. As a kind of flavonoids, aurones are widely distributed in many plants which provide yellow color to some popular ornamental flowers. For a long time aurones had not got enough attention, while in recent years, finally this chemical is coming into researchers' view. As the secondary metabolite in the family of flavonoids, aurones displayed various biological activities, including antioxidant, antiparasitic, antitumor, antiviral, antibacterial, anti-inflammatory, anti-SARS-CoV-2 and neuropharmacological activities. Therefore, aurones have attracted the attention of more and more chemists and pharmaceutical chemists, who realized that it is possible to get lead compounds with better activities via structural modifications of aurones. In some research works, aurone and its derivatives have exhibited good activity, e.g., Xie discovered the heterocyclic variant of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)- one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, and absence of appreciable toxicity, which proved that aurones are valuable compounds worthy of further study. Herein, the biological activities of aurone derivatives are reviewed, which covers the literature since 2000, in which the strategies to develop bioactive aurone derivatives and the structureactivity relationship are highlighted.

Preparation of poly(vinyl alcohol) with enhanced stereoselectivity via hydrolysis of poly(vinyl acetate) produced by radical polymerization using 7-membered ring controlling agents

Controlling tacticity is crucial in polymer chemistry since it impacts the characteristics of synthetic polymers. Poly(vinyl alcohol) (PVA), generally obtained by hydrolysis of poly(vinyl acetate) (PVAc), is a prevalent polymer whose properties are susceptible to even a small change in the main chain stereostructure. Thus, new polymerization methods that improve the tacticity of PVA or its precursor polymer are highly desirable. Herein, 7-membered ring compounds (tropolone (Tro-H), 2-tosyloxytropone (Tro-OTs), potassium tropolonate (Tro-K), methanesulfonic acid, 1,1,1-trifluoro-,7-oxo-1,3,5-cycloheptatrien-1-yl ester (Tro-OTf), potassium 4-((7-oxocyclohepta-1,3,5-trien-1-yl)oxy)butane-1-sulfonate (Tro-SO3K) are explored for the first time as controlling agents for the radical polymerization of VAc with azobisisobutyronitrile (AIBN) as initiator. The obtained PVAc was hydrolyzed to obtain PVA. Process parameters such as monomer concentration, amount of controlling agent and initiators were optimized. The results revealed that the hydrolysis of PVAc produced in the presence of controlling agents gave PVA with improved stereoselectivity. Higher stereoselectivity, that is, isotactic triad (mm) = 24.24% of PVA, was obtained by the hydrolysis of PVAc produced with Tro-SO3K compared to VAc polymerization with other controlling agents. Moreover, hydrolysis of PVAc produced with Tro-SO3K under a wavelength radiation source (λmax, 365 nm) gave PVA with increased mm to 24.59% under similar conditions. In addition, flow chemistry, an emerging technology, was also used for VAc polymerization under optimized reaction conditions to obtain PVA with a mm of 24.62%. This work therefore provides an effective strategy to produce PVA with improved stereoselectivity via both batch and continuous flow techniques, enabling technical advantages for potential large-scale uses.