Vinyl Moiety Research Articles

Borrelidins F–I, cytotoxic and cell migration inhibiting agents from mangrove-derived Streptomyces rochei SCSIO ZJ89

Borrelidin A (1) is produced by several species of Streptomyces and within its bioactive scaffold, the vinylic nitrile moiety is essential for activity. We report herein newly discovered members of the borrelidin family, borrelidin F (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated from Streptomyces rochei SCSIO ZJ89 originating from a mangrove-derived sediment sample. These structurally diverse metabolites enabled a number of new structure-activity relationships (SARs) to be identified, especially with respect to the different configurations at the C11-OH and C12–C15 double bonds for which the absolute configurations were determined using spectroscopic methods. Importantly, borrelidin H (4) was found to have a therapeutic window superior to that of borrelidin A (1) in vitro and could inhibit migration of cancer cells.

Total Synthesis and Structural Determination of XR774, a Tyrosine Kinase Inhibitor.

Total synthesis and structural determination of XR774 has been accomplished. The benzo[ j]fluoranthene skeleton has been constructed by regioselective coupling between tetraline 3 and tetralone 4 successively followed by the sequential transformation including the Birch reduction to prepare allylic alcohol, simultaneous bromination of vinylic and aromatic moieties, and the nickel-mediated intramolecular coupling reaction. The optical resolution of racemic 17 led to the first total synthesis of (-)-XR774.

Regioselectivity in Reactions between Bis(2-benzothiazolyl)ketone and Vinyl Grignard Reagents: C- versus O-alkylation-Part III.

The reaction between bis(2-benzothiazolyl)ketone and vinyl Grignard reagents bearing different substituents on the vinyl moiety gave the product derived from attack on the carbonylic carbon- and/or oxygen-atom. The regioselectivity of the attack depends on the kind of substituents bound to the vinylic carbon atoms and on their relative position. The reaction between vinylmagnesium bromide and 2-methyl-1-propenylmagnesium bromide was carried out under different experimental conditions and in the presence of radical scavengers. The results indicate a plausible mechanistic pathway involving radical intermediates in the case of O-alkylation, but a polar ones in the case of classic C-alkylation. This agrees with our previous reports indicating a key role played by the delocalization ability of the substituents bound to the carbonyl group in driving the regioselectivity of the vinylmagnesium bromide attack towards O-alkylation. Further support of this was obtained by diffractometric analysis of four distinct bis(heteroaryl)ketones.

Magnetic Interaction Observed in Hetero Biradical Derivatives Containing a 2,2,5,5-Tetramethylpyrrolin-1-yloxyl Unit as a Localized Spin Center.

The magneto-structural correlation of hetero biradical derivatives containing a 2,2,5,5-tetramethylpyrrolin-1-yloxyl unit as a localized spin center and a verdazyl or nitronyl nitroxide radical is reported. The magnetic susceptibility measurement revealed that the verdazyl attached biradical 1 exhibits ferromagnetic interaction, whereas antiferromagnetic interaction is observed for nitronyl nitroxide attached biradical 2. An EPR study in toluene glass matrix suggests that both 1 and 2 have a ground triplet state. DFT calculations predict that there is intramolecular ferromagnetic interaction for both biradicals. The computation also suggests that the intramolecular magnetic interaction is weaker with larger dihedral angle between pyrroline ring and verdazyl ring/O-N-C-N-O plane of nitronyl nitroxide. The computations of model compounds 3 and 4 suggest that spin polarization on vinylic moiety without distribution of SOMO might be an essential condition for the intramolecular ferromagnetic interaction.

Inherently flame retardant vinyl bearing hyperbranched polysiloxanes having improved thermal stability-Ceramization and analysis of associated thermal properties

This study describes the synthesis and characterization of novel hyperbranched silicone polymers having high thermal stability and inherent flame retardancy achieved purely by molecular architecture, without the incorporation of any specific additive or filler. A series of hyper-branched terpolymers (MeDPhDViT) containing vinyl, phenyl and methyl moieties were synthesized by the acid catalysed copolymerization of vinyltriethoxysilane (VTES), diphenyldimethoxysilane (DPDMS) and dimethyldiethoxysilane (DMDES). Curing of these polymers is effected through condensation of the hydroxyl groups triggered by dibutyltindiluarate (DBTDL) catalyst. Glass to rubber transition temperature (Tg)of the cured polymers vary systematically from −110 °C to +50 °C with the increase in the content of vinyl T (ViT) units in the polymer backbone. The terpolymer with maximum ViT-unit content shows an onset of thermal decomposition above 540 °C and leaves 86% char residue at 900 °C, attributed to the retardation of depolymerisation by ViT unit. The limiting oxygen index (LOI) of the terpolymers increases from 26 to 37% with increase in ViT unit content alone, from 13.4 to 53.3 mol% and the terpolymer with 53.3 mol % ViT unit rates as V-0, the best in the UL-94 flame test. The ceramic residue from the cured elastomer comprises of free carbon and silica/Si-O-C ceramics. A probable mechanism has been proposed for the rearrangement of vinyl groups to carbonaceous ceramics under high temperature environment. The vinyl groups promote the formation of a carbonized, in particular graphitized, layer and SiOC phases during pyrolysis, as evidenced by TG-MS, pyrolysis GC-MS, Raman spectroscopy and FESEM analysis. Comparative study with a non-phenylated silicone elastomer confirms the mechanism of formation of carbon rich residue by the thermal rearrangement of vinyl groups.

Biodegradation of gamma irradiated poly-3-hydroxybutyrate/sepiolite nanocomposites

The influence of different doses of gamma irradiation on the physical and biodegradation properties of poly-3-hydroxybutyrate/sepiolite (PHB/SP) nanocomposites has been investigated. The sepiolite was modified with vinyltriethoxy silane (VTES) to enhance its compatibility with PHB. The scanning electron micrographs of nanocomposite films showed a good network formation. The infrared spectra of irradiated nanocomposite films indicated a significant decrease in the intensities of peaks observed at 2933 and 2859 cm−1 (CH stretching vibrations of the vinyl moieties) with an increase in the absorption dose. Thermal stability of nanocomposite films was increased as compared to the PHB. The unirradiated and irradiated nanocomposite films were subjected to in-vitro and soil burial biodegradation studies. Scanning electron micrographs showed the formation of biofilm, agglomerates and pits on the surfaces of nanocomposite films after soil burial. The biodegradation process of nanocomposite films was further confirmed by a sharp reduction in the intensities of IR peaks found at 3658-3045 cm−1 (OH stretching), 1720 cm−1 (the carbonyl ester stretching), 1456 cm−1 (anti-symmetric bending vibration of CH bonds) and 1275 cm−1 (C-O-C stretching). These results suggest the possible application of the PHB/SP nanocomposite film as a biodegradable food packaging material.

Tyrosine-derived novel antimicrobial hydantoin polymers: synthesis and evaluation of anti-bacterial activities

A new approach for the design and synthesis of cyclic N-halamine polymers having anti-bacterial activity based on a vinyl derivative of tyrosine-derived hydantoin is reported. The synthesis of N-halamine polymers generally involves the chemical modification of 5,5′-disubstituted hydantoin to introduce polymerizable vinyl moieties thereby restricting the halogen capture only on the amide nitrogen. Here we show the possibility of synthesizing vinyl monomers of N-halamine from α-amino acids wherein both the amide and imide nitrogens are available for halogen capture. Thus, a hydantoin monomer was synthesized from L-tyrosine and copolymerized with methyl methacrylate and 2-(hydroxyethyl)methacrylate, to obtain random co-polymers. The monomer and its co-polymers were characterized using NMR, IR, HRMS, GPC, DSC, EDAX and TGA analysis. Films of the co-polymers cast from 10% acetone solutions were exposed to sodium hypochlorite solution to activate the hydantoin moieties. The oxidative chlorine content of the films ranged from 0.6 to 0.9%. The activated films were exposed to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria using standard protocols. Polymers having chlorine content as little as 0.6% exhibited 6 log reduction in the bacterial growth within 30 min of exposure. The method allows the halogenation of both amide and imide nitrogens and could be applied to the preparation of a number of vinyl hydantoins from many amino acids.

Short Enantioselective Total Synthesis of (-)-Rhazinilam Using a Gold(I)-Catalyzed Cyclization.

(R)-(-)-Rhazinilam has been synthesized in nine steps and 20% overall yield. The key steps involve two metal-catalyzed processes: the enantioselective gold(I)-catalyzed cycloisomerization of an allene-functionalized pyrrole and the palladium-catalyzed hydrocarboxylation of a vinyl moiety with formate as a CO surrogate. This novel strategy represents the shortest and highest yielding enantioselective total synthesis of (-)-rhazinilam.

Enantioselective Construction of Trifluoromethoxylated Stereogenic Centers by a Nickel‐Catalyzed Asymmetric Suzuki–Miyaura Coupling of Secondary Benzyl Bromides

Trifluoromethoxy-substituted stereogenic centers can be constructed with high enantioselectivity by a nickel-catalyzed Suzuki-Miyaura coupling of readily available α-bromobenzyl trifluoromethyl ethers with a variety of aryl pinacol boronates. The coupling proceeds under mild reaction conditions, and a variety of common functional groups, such as fluoride, chloride, bromide, ester, enolizable ketone, nitro, cyano, amino, and vinyl moieties, were well tolerated. Furthermore, the reaction can be easily scaled up to gram quantities without a decrease in enantioselectivity.

Enantioselective Construction of Trifluoromethoxylated Stereogenic Centers by a Nickel‐Catalyzed Asymmetric Suzuki–Miyaura Coupling of Secondary Benzyl Bromides

AbstractTrifluoromethoxy‐substituted stereogenic centers can be constructed with high enantioselectivity by a nickel‐catalyzed Suzuki–Miyaura coupling of readily available α‐bromobenzyl trifluoromethyl ethers with a variety of aryl pinacol boronates. The coupling proceeds under mild reaction conditions, and a variety of common functional groups, such as fluoride, chloride, bromide, ester, enolizable ketone, nitro, cyano, amino, and vinyl moieties, were well tolerated. Furthermore, the reaction can be easily scaled up to gram quantities without a decrease in enantioselectivity.

Fe(II)-Catalyzed Isomerization of 4-Vinylisoxazoles into Pyrroles.

The first synthesis of pyrroles by Fe(II)-catalyzed isomerization of 4-vinylisoxazoles is reported. 5-Alkoxy, amino, and N,N-dialkylamino-3-aryl/alkyl-4-(2-R-vinyl)isoxazoles afford 2-aryl/alkyl-5-aryl/alkyl/methoxycarbonyl-1H-pyrrol-3-carboxylic acid derivatives typically under mild conditions with cheap and available FeCl2·4H2O as a catalyst. The isomerization of 5-alkoxy/amino-3-arylisoxazoles, bearing unsaturated carbo and heterocyclic substituents at the position 4, gives the corresponding fused pyrrolecarboxylic acid derivatives in high yields. DFT calculations were used to elucidate a probable mechanism of the isomerization and explain the influence of steric congestion of the vinyl moiety on the isomerization pathway.

Replacement of benzylic hydroxy group by vinyl or hydroxymethyl moiety at the 3-benzazepine scaffold retaining GluN2B affinity

Since overactivation of NMDA receptors is associated with neurodegenerative disorders, the design and development of subunit-selective NMDA receptor antagonists are of great interest. In order to avoid the formation of quinone-like intermediates as starting point for degradation the benzylic OH group of the lead compounds 2 was replaced by an electron rich vinyl or homologous hydroxymethyl moiety. The Bi(OTf)3 catalyzed intramolecular Friedel-Crafts alkylation of 9a represents the key step in the synthesis of 1-vinyl substituted tetrahydro-3-benzazepine 10. Ozonolysis of 10 and subsequent reduction led to the hydroxymethyl derivative 14. The GluN2B affinities of the methyl ethers 2a, 3a and 4a and phenols 2b and 3b are very similar, respectively. It can be concluded that the ifenprodil binding site of GluN2B subunit containing NMDA receptors well tolerates a vinyl or hydroxymethyl moiety instead of the benzylic OH group. However, the selectivity has to improved, since the σ1 affinity of the new ligands is higher than their GluN2B affinity.

The Conjugated Double Bond of Coniferyl Aldehyde Is Essential for Heat Shock Factor 1 Mediated Cytotoprotection

Coniferyl aldehyde (1) is previously reported as a potent inducer of heat shock factor 1 (HSF1). Here, we further examined the active pharmacophore of 1 for activation of HSF1 using the derivatives coniferyl alcohol (2), 4-hydroxy-3-methoxyphenylpropanal (3), and 4-hydroxy-3-methoxyphenylpropanol (4). Both 1 and 2 resulted in increased survival days after a lethal radiation (IR) dose. The decrease in bone marrow (BM) cellularity and Ki67-positive BM cells by IR was also significantly restored by 1 or 2 in mice. These results suggested that the vinyl moiety of 1 and 2 is necessary for inducing HSF1, which may be useful for developing small molecules for cytoprotection of normal cells against damage by cytotoxic drugs and radiation.

One‐Pot Vinylation of Azlactones: Fast Access to Enantioenriched α‐Vinyl Quaternary Amino Acids

We report a fast one‐pot protocol for the direct vinylation of azlactones [oxazol‐5‐(4H)‐ones] by using as a key step an aldol addition with 2‐(phenylselenenyl)acetaldehyde followed by dehydroxyselenation. The acid hydrolysis of the oxazolone ring gave the desired fully deprotected α‐vinyl quaternary α‐amino acids in almost quantitative yields. An enantioselective variant of the method was also developed by using catalytic chiral bases. The use of Sharpless ligand (DHQD)2PHAL produced the final quaternary amino acids in good overall yields (62–78 %) and with ee values up to 86 %. Scaling up the optimized protocol to gram quantities did not affect the yields and ee values. We also demonstrated that the vinyl moiety installed onto the oxazolone ring can be exploited as a handle for the attachment of aryl groups through a Heck coupling reaction.

Palladium-Catalyzed Oxidative Annulation of ortho-Alkenylanilines and Allenes: An Access to Benzo[b]azepines.

Palladium-catalyzed oxidative annulation of ortho-alkenylanilines and allenes to constitute valuable, but synthetically challenging, benzo[b]azepines has been developed. The procedure, involving the cleavage of the terminal C(sp2)-H bond of the vinyl moiety and the participation of allenes as two-carbon cycloaddition partner, is attractive in terms of assembly efficiency and environmental friendliness. The transformation features mild reaction conditions and good functional group tolerance, resulting in a variety of benzo[b]azepines in good to excellent yields.

Capitalizing on Protecting Groups to Influence Vinyl Catechol Monomer Reactivity and Monomer Gradient in Carbanionic Copolymerization

Several vinyl catechol‐based monomers with systematically varied acetal protecting groups suitable for carbanionic polymerization are introduced. All monomers are based on the 4‐vinyl benzodioxole or 5‐vinyl benzodioxole structure and differ in the nature of the protecting group for the catechol functionalities. Different symmetric ketones are used for the protection of the diol functionality. Polymers with average molecular weight from 2500 to 25 000 g mol−1 (Mw/Mn < 1.15) are obtained from homopolymerization of the protected monomers. All monomers are examined regarding the influence of the protecting group on the copolymerization behavior with styrene, using in situ 1H NMR kinetic studies. Length and structure of the alkyl chains generally show no influence for all monomers based on 5‐vinyl benzodioxole. In contrast, all monomers with the protecting group in direct vicinity to the propagating vinyl moiety exhibit dependence between monomer reactivity and chain length of the protecting group. A decrease of the monomer reactivity enables control of the gradient in the copolymerization with styrene. Finally, the first terpolymerization kinetics of a carbanionic polymerization in 1H NMR kinetics is presented, combining the monomers 3‐vinyl catechol acetonide, styrene, and 4‐vinyl catechol acetonide, which enables the one‐pot synthesis of double gradient terpolymers. image

4-(Azulen-1-yl) six-membered heteroaromatics substituted in 2- and 6- positions with 2-(2-furyl)vinyl, 2-(2-thienyl)vinyl or 2-(3-thienyl)vinyl moieties

The synthesis of pyrylium and pyridinium salts and pyridines with azulene-1-yl moieties in position 4 and two 2-heteroarylvinyl groups in positions 2 and 6 was accomplished. The pyrylium salts were obtained starting from pyranones and pyridines could be prepared from these salts by treating them with ammonium acetate. The general procedures for the synthesis of pyridinium salts, which occur with good results in less delocalized electronic systems, do not take place when applied to the above obtained pyrylium salts. Therefore, as starting material 4-(azulen-1-yl)-1-(n-butyl)-2,6-dimethylpyridinium perchlorate was used, which was condensed with heteroarylcarboxaldehydes. These compounds were completely characterized and some of their spectra were discussed. Their interaction with some metal ions was revealed, observing an affinity better than in the case of simple azulenepyridines. In the last part of the paper are presented redox potentials for several pyrylium salts and pyridines in comparison with those of the nonvinylogated derivatives.

Insights into the origin of aggregation enhanced emission of 9,10-distyrylanthracene derivatives

Intramolecular rotation around the vinyl moiety plays an important role in the whole AIE process of DSA derivatives.

NMR SLIC Sensing of Hydrogenation Reactions Using Parahydrogen in Low Magnetic Fields.

Parahydrogen-induced polarization (PHIP) is an NMR hyperpolarization technique that increases nuclear spin polarization by orders of magnitude, and it is particularly well-suited to study hydrogenation reactions. However, the use of high-field NMR spectroscopy is not always possible, especially in the context of potential industrial-scale reactor applications. On the other hand, the direct low-field NMR detection of reaction products with enhanced nuclear spin polarization is challenging due to near complete signal cancellation from nascent parahydrogen protons. We show that hydrogenation products prepared by PHIP can be irradiated with weak (on the order of spin–spin couplings of a few hertz) alternating magnetic field (called Spin-Lock Induced Crossing or SLIC) and consequently efficiently detected at low magnetic field (e.g., 0.05 T used here) using examples of several types of organic molecules containing a vinyl moiety. The detected hyperpolarized signals from several reaction products at tens of millimolar concentrations were enhanced by 10000-fold, producing NMR signals an order of magnitude greater than the background signal from protonated solvents.

Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study).

Thiol reagents were shown to act as potent inhibitors of L5178-Y murine leukemia cell proliferation. A series of aryl maleimides (AMI) was synthesized and evaluated theoretically for global and local reactivity, showing their selectivity for thiol groups, due to a reaction of the vinyl moiety (a soft acid) with thiols (a soft base). Two AMI that are benzoic acid derivatives (1f and 1h) were tested with an in vitro and ex vivo model to evaluate their reactivity with thiols and their activity in L5178-Y cells. The in vitro reactions clearly showed a selective Michael type 1,4-addition reaction between thiols (glutathione and N-acetylcysteine, which are nucleophiles) and the AMI (1f and 1h, which are electrophiles). In cell cultures, the compounds induced a decreasing cellular viability and an apoptotic effect of up to 59.8% at 48 h. The ex vivo experimental model showed an important reduction of thiol levels in cells treated with 1h. Decreased cellular viability and increased apoptosis were confirmed by flow cytometry, DNA fragmentation and microscopy analysis (cytological studies). The increase in apoptosis on L5178-Y cells probably occurred, at least in part, by a decrease in glutathione levels and an increase in free radicals concentration. The decreased glutathione levels seem to make cancer cells more susceptible to death by apoptosis, and should certainly make them more vulnerable to a less aggressive treatment.