Urethane Derivatives Research Articles

Synthesis and liquid crystalline behavior of three-arm urethane derivatives bearing protruded alkyoxylbiphenyls

Here, we describe an approach to synthesis of three-arm urethane derivatives bearing alkyloxybiphenyl units. Four new families of oligomers derived from 1,6-hexamethylene diisocyanate and their di- or trimers (uretdione, biuret or isocyanurate) and ω-hydroxyalkylated biphenyls were prepared. Their mesomorphic and optical properties were investigated by differential scanning calorimetry and POM. Mesomorphic properties were substantially impacted by the structure of the central core spacer (urethane, uretdione, biuret, or isocyanurate). The synthesized compounds shown the rich smectic polymorphism form from one to three different smectic phase. Stabilization of the LC state of synthesized oligomers was attributed to the H-bonding interactions confirmed by FT-IR spectra. The part of H-bonded urethane units is maximal for compounds with star-shaped central core.

Can Modification with Urethane Derivatives or the Addition of an Anti-Hydrolysis Agent Influence the Hydrolytic Stability of Resin Dental Composite?

Can Modification with Urethane Derivatives or the Addition of an Anti-Hydrolysis Agent Influence the Hydrolytic Stability of Resin Dental Composite?

Can Modification with Urethane Derivatives or the Addition of an Anti-Hydrolysis Agent Influence the Hydrolytic Stability of Resin Dental Composite?

Due to the questionable durability of dental restorations, there is a need to increase the lifetime of composite restoration. The present study used diethylene glycol monomethacrylate/4,4'-methylenebis(cyclohexyl isocyanate) (DEGMMA/CHMDI), diethylene glycol monomethacrylate/isophorone diisocyanate (DEGMMA/IPDI) monomers, and bis(2,6-diisopropylphenyl)carbodiimide (CHINOX SA-1) as modifiers of a polymer matrix (40 wt% urethane dimethacrylate (UDMA), 40 wt% bisphenol A ethoxylateddimethacrylate (bis-EMA), and 20 wt% triethyleneglycol dimethacrylate (TEGDMA)). Flexural strength (FS), diametral tensile strength (DTS), hardness (HV), sorption, and solubility were determined. To assess hydrolytic stability, the materials were tested before and after two aging methods (I-7500 cycles, 5 °C and 55 °C, water and 7 days, 60 °C, 0.1 M NaOH; II-5 days, 55 °C, water and 7 days, 60 °C, 0.1 M NaOH). The aging protocol resulted in no noticeable change (median values were the same as or higher than the control value) or a decrease in the DTS value from 4 to 28%, and a decrease in the FS value by 2 to 14%. The hardness values after aging were more than 60% lower than those of the controls. The used additives did not improve the initial (control) properties of the composite material. The addition of CHINOX SA-1 improved the hydrolytic stability of composites based on UDMA/bis-EMA/TEGDMA monomers, which could potentially extend the service life of the modified material. Extended studies are needed to confirm the possible use of CHINOX SA-1 as an antihydrolysis agent in dental composites.

Self-Healable, Injectable Hydrogel with Enhanced Clotrimazole Solubilization as a Potential Therapeutic Platform for Gynecology.

Injectable, self-healing hydrogels with enhanced solubilization of hydrophobic drugs are urgently needed for antimicrobial intravaginal therapies. Here, we report the first hydrogel systems constructed of dynamic boronic esters cross-linking unimolecular micelles, which are a reservoir of antifungal hydrophobic drug molecules. The selective hydrophobization of hyperbranched polyglycidol with phenyl units in the core via ester or urethane bonds enabled the solubilization of clotrimazole, a water-insoluble drug of broad antifungal properties. The encapsulation efficiency of clotrimazole increases with the degree of the HbPGL core modification; however, the encapsulation is more favorable in the case of urethane derivatives. In addition, the rate of clotrimazole release was lower from HbPGL hydrophobized via urethane bonds than with ester linkages. In this work, we also revealed that the hydrophobization degree of HbPGL significantly influences the rheological properties of its hydrogels with poly(acrylamide-ran-2-acrylamidephenylboronic acid). The elastic strength of networks (GN) and the thermal stability of hydrogels increased along with the degree of HbPGL core hydrophobization. The degradation of the hydrogel constructed of the neat HbPGL was observed at approx. 40 °C, whereas the hydrogels constructed on HbPGL, where the monohydroxyl units were modified above 30 mol %, were stable above 50 °C. Moreover, the flow and self-healing ability of hydrogels were gradually decreased due to the reduced dynamics of macromolecules in the network as an effect of increased hydrophobicity. The changes in the rheological properties of hydrogels resulted from the engagement of phenyl units into the intermolecular hydrophobic interactions, which besides boronic esters constituted additional cross-links. This study demonstrates that the HbPGL core hydrophobized with phenyl units at 30 mol % degrees via urethane linkages is optimal in respect of the drug encapsulation efficiency and rheological properties including both self-healable and injectable behavior. This work is important because of a proper selection of a building component for the construction of a therapeutic hydrogel platform dedicated to the intravaginal delivery of hydrophobic drugs.

Synthesis and evaluation of antibacterial and trypanocidal activity of derivatives of monensin A

The synthesis and biological evaluation of eleven derivatives of the natural polyether ionophore monensin A (MON), modified at the C-26 position, is presented. Eight urethane and three ester derivatives were tested for their antimicrobial activity against different strains of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa. In addition, their antiparasitic activity was also evaluated with bloodstream forms of Trypanosoma brucei. The majority of the modified ionophores were active against a variety of Gram-positive bacterial strains, including methicillin-resistant S. epidermidis, and showed better antibacterial activity than the unmodified MON. The phenyl urethane derivative of MON exhibited the most promising antibacterial activity of all tested compounds, with minimal inhibitory concentration values of 0.25–0.50 μg/ml. In contrast, none of the MON derivatives displayed higher antitrypanosomal activity than the unmodified ionophore.

Amphiphilic Co-polypeptides Self-Assembled into Spherical Nanoparticles for Dermal Drug Delivery

Poly(l-glutamic acid)-b-poly(Nγ-acetyl-l-2,4-diaminobutyric acid), P(Glu-b-NADA), amphiphilic block-co-polypeptides with different hydrophobic/hydrophilic ratios were synthesized as drug carriers for dermal delivery. The block-co-polypeptides were prepared using ring-opening polymerization (ROP) of γ-benzyl l-glutamate N-carboxyanhydride and polycondensation of the activated urethane derivative of Nγ-acetyl-l-2,4-diaminobutyric acid. Structures and conjugations of two blocks were successfully confirmed by 1H NMR, FTIR, DOSY NMR, GPC, and TGA. The nanocarriers were loaded with 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (m-THPP), a close congener of the approved photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)chlorin (m-THPC, temoporfin), and the loading capacity was found to be dependent on the composition of the block-co-polypeptides. Among the synthesized polymers, P(Glu55-b-NADA20) with moderate hydrophobic content showed the highest drug loading capacity of 4 wt % and self-aggregated into spherical nanoparticles with a size of 180–200 nm, which was confirmed by TEM and DLS. In an in vitro drug release study, P(Glu55-b-NADA20) could release m-THPP in a controllable manner. Furthermore, the synthesized polymer P(Glu55-b-NADA20) did not show high toxicity against HaCaT and HeLa cells up to 1000 and 500 μg mL–1, respectively, in an in vitro cell viability assay. Finally, it was shown in an ex vivo skin penetration study that the ionic amphiphilic block co-polypeptide enhanced the m-THPP penetration into human skin compared to base cream up to a factor of 12. m-THPP was released from P(Glu55-b-NADA20) to the viable epidermis while the polymer was deposited in the skin’s stratum corneum. Taking advantage of its excellent biodegradability, the low cytotoxcity, and efficient skin penetration, the synthesized block-co-polypeptide has the potential for future topical delivery systems.

Lossen Rearrangement of p-Toluenesulfonates of N-Oxyimides in Basic Condition, Theoretical Study, and Molecular Docking.

The sulfonic esters of N-oxyimides are a group of compounds with a wide range of biological activities, as well as a unique reactivity toward amines. They undergo this reaction with primary amines and other nucleophilic reagents according to a Lossen-like rearrangement. The reaction is initiated by nucleophilic attack on a carbonyl group in the succinimide ring followed by isocyanate formation, which next interacts with another nucleophile molecule forming an addition product (e.g., ureido or urethane derivative). However, the secondary amines are also susceptible to other reactions leading to products containing the maleimide ring formed by sulphonic acid elimination. In the case of tertiary amines, this reaction is predominant. To explain the phenomenon of the reactivity of the N- oxyimides toward different types of amines, we employed various spectroscopic and X-ray approaches as well as DFT calculation. Results suggest that the basicity of the amine used for the reaction plays a crucial role in the reaction mechanism that eventually dominates the entire chemical process. Moreover, we applied molecular docking to investigate the ability of the products to act as serine protease inhibitors using human leukocyte elastase (HLE).

Well-Defined Construction of Functional Macromolecular Architectures Based on Polymerization of Amino Acid Urethanes.

Polypeptide synthesis was accomplished using the urethane derivatives of amino acids as monomers, which can be easily prepared, purified, and stored at ambient temperature without the requirement for special precautions. The urethanes of amino acids are readily synthesized by the N-carbamoylation of onium salts of amino acids using diphenyl carbonate (DPC). The prepared urethanes are then efficiently cyclized to produce amino acid N-carboxyanhydrides (NCAs). Thereafter, in the presence of primary amines, the ring-opening polymerization (ROP) of NCAs is initiated using the amines, to yield polypeptides with controlled molecular weights. The polypeptides have propagating chains bearing reactive amino groups and initiating chain ends endowed with functional moieties that originate from the amines. Aiming to benefit from these interesting characteristics of the polypeptide synthesis using the urethanes of amino acids, various macromolecular architectures containing polypeptide components have been constructed and applied as biofunctional materials in highly efficient antifouling coatings against proteins and cells, as biosensors for specific molecules, and in targeted drug delivery.

Cover Image, Volume 69, Issue 3

The cover image is based on the Mini‐Review Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications by Takeshi Endo et al., https://doi.org/10.1002/pi.5952.Cover image © Takeshi Endo Images. image

Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications

AbstractIn this study, both naturally occurring and artificial amino acids were successfully transformed into the corresponding urethane derivatives using diphenyl carbonate. The urethanes thus prepared could be efficiently cyclized into amino acid N‐carboxyanhydrides (NCAs) without the requirement of phosgene. In addition, the presence of primary amines converted the urethane derivatives into NCAs and initiated the ring‐opening polymerization of the in situ formed NCAs, allowing for the well‐defined synthesis of polypeptides. These polypeptides contained initiating ends functionalized by an amine‐derived residue and propagating ends bearing the reactive amino group. By precise control of the structures of the polypeptides, various polypeptide conjugates such as block copolymers and graft copolymers were successfully synthesized as designed, and their applications in antifouling coatings against proteins, drug delivery systems and biosensors were demonstrated. © 2019 Society of Chemical Industry

Features of the modification of polylactide by (meth)acrylate groups in organic solvents

Polymerizable (meth)acrylate groups were introduced into polylactide (PLA) in the methylene chloride or toluene medium. Polymer modification was carried out both on the carboxyl and hydroxyl groups of polylactide. The efficiency of this modification was studied depending on the type of reaction. It was found that the highest degree of polylactide modification by (meth)acrylate groups (86%) is achieved through the formation of PLA urethane derivatives in the presence of diisocyanates. Samples of photocured, three-dimensionally crosslinked after such a modification polylactides were obtained, their biocompatibility was determined. It was shown that such materials are promising for use in regenerative medicine and tissue engineering.

Green synthesis of in situ forming alginate-urethane hydrogel through Schiff base reaction

Despite recent advances in preparing hydrogels, their application is mainly limited due to the poor mechanical properties or the high risk of inflammatory response. Therefore, in this study a fully defined in situ hydrogelation system is developed based on green-chemistry in which alginate dialdehyde (ADA) was coupled to an isocyanate-free urethane derivative. FTIR analysis along with 1HNMR confirmed hydrogel formation. Improved thermal stability of the hydrogel was an indication of hydrogen bonding at various sites. The microgels possessed the mean diameter of 4 microns, reasonable gelation time and suitable biocompatibility which made them prospective candidates for various fields of biomedicine.

Synthesis of poly(Nε‐phenoxycarbonyl‐l‐lysine) by polycondensation of activated urethane derivative and its application for selective modification of side chain with amines

ABSTRACTWe report a methodology for the synthesis of Nε‐phenoxycarbonyl‐protected poly(l‐lysine) on the side chain by chain growth polycondensation of Nα,Nε‐bis(phenoxycarbonyl)‐l‐lysine proceeded through the selective elimination of phenol and CO2 from the Nα phenoxycarbonyl moiety at 50 °C in N,N‐dimethylacetamide in the presence of a primary amine used as an initiator. After optimization of reaction condition, the addition of acetic acid during polycondensation proved effective for the realization of the predicted molecular weight and narrow dispersity of the corresponding polypeptide by adjusting the feed ratio of monomer to the amine initiator because of the suppression of interchain coupling that occurs between the amino terminus of poly(l‐lysine) and the Nε‐phenoxycarbonyl group on the polymer side chains. Furthermore, taking advantage of the potentially reactive Nε‐phenoxycarbonyl moiety on the side chain, post‐polymerization modification was effectively achieved by the nucleophilic reaction of amine compounds including primary, secondary, and aromatic amines through the formation of urea linkage, providing a useful platform for synthesis of selective side chain functionalization of poly(l‐lysine) samples. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2522–2530

Synthesis of Monodisperse Naphthalene Dendrons for the Application of Dendrimers

Syntheses of dendrons for dendrimer applications are described using napthyl and urethane derivatives. The napthol, 1-(3-hydroxy-6-(methoxymethoxy)naphthalen-1-yl)ethan-1-one (h), was synthesized by employing Au-catalyzed cyclization of the corresponding propargylic carboxylates. Polynapthol dendrons (i, j, k, and l) were prepared from substitution reactions of napthyl derivative h with alkyl/aryl halides under basic conditions. Branched polyurethane compounds (q, r, and s) were also prepared from addition reactions of 1,3,5-tris(6-isocyanteohexyl)-1,3,5-triazine-2,4,6-trione (p) with various alcohols under Lewis acidic conditions. The photophysical properties of the synthesized compounds h, k, and j were studied.

α-Amino acid N-thiocarboxyanhydrides: A novel synthetic approach toward poly(α-amino acid)s

Poly(α-amino acid)s, containing amino acid repeat units, are remarkable biomaterials with similar structures to protein, which are mainly synthesized by solid phase peptide synthesis, ring opening polymerization of N-carboxyanhydrides, polymerization of activated urethane derivatives of α-amino acids and so on. α-Amino acid N-thiocarboxyanhydride (NTA) and N-substituted glycine N-thiocarboxyanhydride (NNTA) have recently emerged as a subject of scientific interest due to their easy synthesis and purification in open air, long shelf-life and well controlled polymerization to produce poly(α-amino acid)s. In this feature article, we review the history and the recent development on the design of NTA monomers, and summarize the recent advances in poly(α-amino acid)s synthesis through ring-opening polymerization of NTA and NNTA by using different initiators and reaction mediums. We also highlight the applications of poly(α-amino acid) materials resulting from NTA polymerization.

Facile ring opening reaction of oxazolone enables efficient amidation for aminoisobutyric acid.

4,4-Dimethyloxazolones derived from N-protected aminoisobutyric acid (AIB) are particularly known as poor electrophiles due to the steric hindrance around the carbonyl and not employed as useful intermediates for amidation whereas numerous examples have been reported to support the utility of other oxazolones in amidation. AIB is an important and strategical synthon in medicinal chemistry but the peptide bond formation of the N-protected urethane derivatives of AIB is known to be often unproductive due to the rapid formation of the stable 4,4-dimethyloxazolone via an intramolecular cyclization. We discovered that the 4,4-dimethyloxazolone of an AIB urethane is in fact an excellent electrophile that enables efficient amidation even with weakly reactive nucleophiles. The 4,4-dimethyloxazolone can be stored in a pure form and used as a reagent offering an efficient and convenient synthetic tool for generating AIB-peptide analogs.

Synthesis of poly(2-ethyl-2-oxazoline)-block-polypeptide copolymers by combination of ring-opening polymerization of oxazoline and polycondensation of activated urethane derivatives of α-amino acids

In this study, we examined the utilization of a primary-amine-terminated poly(2-ethyl-2-oxazoline) as macroinitiators for the chain-growth polycondensation of activated urethane derivatives of α-amino acids to obtain poly(2-ethyl-2-oxazoline)-block-polypeptide diblock copolymers. To incorporate polypeptide segments into the poly(2-ethyl-2-oxazoline), we prepared four N-phenoxycarbonyl derivatives of α-amino acids, namely, Z-l-lysine, l-alanine, l-phenylalanine, and benzyl-l-serine, which were readily synthesized by N-carbamylation of the tetrabutylammonium salts of the α-amino acids with diphenyl carbonate. We demonstrated that poly(2-ethyl-2-oxazoline)s possessing an amino terminal successfully served as initiators for the chain-growth polycondensation of these urethane derivatives; heating at 60 °C in N,N-dimethylacetamide eliminated phenol and CO2 to give the corresponding diblock copolymers. The structural and thermal properties of the obtained diblock copolymers were determined by FT-IR, 1H NMR, SEC, and TGA.

Cashew tree wood flour activated with cashew nut shell liquid for the production of functionalized composites

This work is aimed at the one-step chemical modification of the surface of cashew wood flour particles using the technical grade cashew nut shell liquid (CNSL). The goal is to develop an alternative way to introduce chemically active sites on the surface of the particles, which allows the addition of new functionalities to such particles. The influence of time and temperature and catalyst on the substitution of lignocellulosic hydroxyls with cardanol/cardol urethane derivatives was evaluated by thermogravimetric analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and contact angle measurements. The mechanical behavior of the modified particles in polypropylene composites was also evaluated by mechanical testing and dynamic mechanical thermal analysis. The FTIR, thermogravimetry, and contact angle results indicated changes on the particle surface, and the mechanical and thermomechanical behavior of the mercerized and modified particles in the composites was found to be similar. These results point that the CNSL approach is a viable way to chemically modify cashew wood flour particle surfaces, while maintaining their properties.

Convenient synthetic approach to poly(N‐Methyl L‐alanine) through polycondensation of activated urethane derivative of N‐methyl L‐alanine

This study describes a convenient and phosgene-free synthesis of poly(N-methyl L-alanine) with solubility in water using polycondensation of activated urethane derivative of N-methyl L-alanine was described. The polycondensation of activated urethane derivative was heated at 60 °C with n-butylamine as an initiator to give the corresponding poly(N-methyl L-alanine), accompanying the elimination of phenol and CO2. The investigation of SEC and MALDI TOF mass spectrometry characterized the control of molecular weight and terminal structure. Additional Supporting Information may be found in the online version of this article. Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Convenient phosgene-free synthesis of polypeptides bearing reactive alkene moiety through polycondensation of activated urethane derivative of α-amino acid

Polypeptides bearing a reactive alkene moiety, including poly-dl-allylglycine (PGly(allyl)) and poly-dl-pentenylglycine (PGly(pent)) have been prepared through the polycondensation of activated urethane derivatives, N-phenoxycarbonyl derivative of α-amino acids. These urethane derivatives of dl-allylglycine (NPC-Gly(allyl)) and dl-pentenylglycine (NPC-Gly(pent)), are prepared by the N-carbamylation of the onium salt of the corresponding α-amino acid with diphenyl carbonate. The polycondensation of urethane derivatives proceeds when heated at 60 °C in N,N-dimethylacetamide, using amines as initiators, along with the elimination of phenol and CO2, to give the corresponding polypeptides without any degradation of alkene moieties. Varying the feed ratio of the urethane derivative to the initiator gives a predictable molecular weight with a narrow polydispersity index. Post-polymerization modifications of the alkene moiety of polypeptide are achieved with a high efficiency through a typical radical thiol-ene addition using a range of thiol-containing compounds, indicating the broad scope of this method as a conjugation tool for functional molecules.