Heterocyclic amines for the construction of peptoid oligomers bearing multi-dentate ligands

Peptoids are oligomers of N-substituted glycine that can be readily assembled using haloacetic acids and primary amines as synthons. Here, we report the synthesis and characterization of three new heterocyclic amines, 2-(2,2′:6′,2″-terpyridine-4′-yloxy)ethylamine, 2-(1,10-phenanthroline-5-yloxy)ethylamine and 8-hydroxy-2-quinolinemethylamine, and their incorporation into a series of different peptoid oligomer sequences. Since the heterocycles are all known to coordinate metal ions, the peptidomimetic products are designed to bind metal species with the potential for applications in catalysis and materials science.     

Expedient synthesis and design strategies for new peptoid construction

[reaction: see text] A range of peptoids can be prepared efficiently using microwave-assisted solid-phase chemistry in a commercial reactor. This method is most effective for the installation of electronically deactivated benzylic amines. The systematic incorporation of these amines into peptoids can deliver oligomers capable of displaying unique and stable structural motifs-microwave-assisted solid-phase synthesis will enable their future study and application.     

Synthesis of Amphiphilic Oligomers of Acrylic Acid

Synthesis of amphiphilic oligomers of acrylic acid via radical polymerization in the presence of thiols as molecular mass regulators is described. The effect of the length of the introduced hydrophobic terminal group on the critical micellization concentration of the acrylic acid oligomers has been elucidated. It has been shown that the incorporation of an antituberculous drug (prothionamide) in the micelles of acrylic acid oligomers is enhanced with the increase in the length of the hydrophobic moiety. The preparation of hydroxyapatite-filled calcium-polycarboxylate bone cements containing prothionamide (promising for the sealing of postoperative cavities) is described.     

Synthesis of Functionalized Glutamine‐ and Asparagine‐Type Peptoids – Scope and Limitations

N‐Alkylated glycine oligomers (‘peptoids’) can serve as potent peptidomimetic systems. Installing different functional groups can often be a challenge, and minimizes yields and purities. Here, we describe the synthesis of different amide‐containing submonomers which were obtained as free bases, as well as their incorporation into peptoids. By using the free amines, the coupling results on solid support could be improved, and various functionalized peptoids were prepared. Additionally, an interesting dimerization side reaction leading to cross‐linked peptoids was observed during synthesis.     

ROMP-generated oligomeric sulfonyl chlorides as versatile soluble scavenging agents

[reaction: see text] A new method for homogeneous nucleophilic scavenging employing oligomeric sulfonyl chloride (OSC) reagents is described. The method utilizes OSC to rapidly scavenge a variety of amines that are present in excess. The OSC reagents are generated from ROM polymerization of 2-chlorosulfonyl-5-norbornene utilizing the second generation Grubbs catalyst to produce oligomers of varying size as stable, free-flowing powders. Following the scavenging event, these oligomers are precipitated with ethyl acetate leaving products in excellent yield and purity.     

Solution- and solid-phase synthesis of triazole oligomers that display protein-like functionality

We recently developed a new class of oligomers that contain alpha-amino acid residues linked by 1,2,3-triazole groups [Angelo, N. G.; Arora, P. S. J. Am. Chem. Soc. 2005, 127, 17134-17135]. Synthesis of these oligomers involves an iterative sequence consisting of diazotransfer and Huisgen 1,3-dipolar cycloaddition steps. In this contribution, we describe an efficient one-pot, two-step sequence for the preparation of triazoles from the corresponding amino acid-derived amines and alkynes in solution. The one-pot sequence affords the desired products in significantly higher yields than our original method. We also outline a highly effective protocol for the synthesis of these triazole-based biomimetic oligomers on the solid phase. We find that amino acid derivatives and iterative formation of triazole rings require nontraditional reaction conditions for high yields.     

Rapid and convenient semi-automated microwave-assisted solid-phase synthesis of arylopeptoids

A facile and expedient route to the synthesis of arylopeptoid oligomers (N-alkylated aminomethyl benz-amides) using semi-automated microwave-assisted solid-phase synthesis is presented. The synthesis was optimized for the incorporation of side chains derived from sterically hindered or unreactive amines and both ortho- and para-substituted arylo-backbones. By utilizing this optimized protocol a complex nonameric arylopeptoid was synthesized in less than 11 h, featuring a novel alternating ortho-, meta-, and para-substituted backbone pattern and a variety of chemically diverse and challenging side chains.     

Syntheses of terminally functionalized polyisobutylene derivatives using diazonium salts

A new strategy for the synthesis of end‐functionalized polyisobutylene (PIB) oligomers is detailed. Commercially available vinyl‐terminated PIB oligomers were modified to form aniline‐terminated PIB via an aromatic electrophilic substitution reaction. The PIB‐bound aryl amines so formed were then converted into diazonium salts using isopentyl nitrite and an acid in methylene chloride. These salts served as versatile intermediates in synthetic reactions affording azo dye‐containing PIB derivatives and other terminally‐functionalized PIB derivatives not readily available by other reactions. The advantages and limitations of various name reactions including diazo couplings, Sandmeyer reactions, dediazoniations, and Heck reactions are discussed. The kinetics of polar substitution reactions at the termini of these nonpolar oligomers and the effects of solvent on these reactions were also examined. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Features of reaction amino-cyclocarbonate for production of new type nonisocyanate polyurethane coatings

We have studied different ways of preparing UV resistant oligomers with terminated cyclocarbonates, epoxy and amino groups. We have studied possibility of preparing HNIPU UV stable coatings. Linear and branched amino containing oligomers based on di- and tricyclocarbonates and primary diamines were investigated. It was found that oligomers should be used for curing epoxy-saturated resins, but since the residual quantity of amines this system can't be used for UV resistant coatings. The same problem was in system on the base of nonisocyanate epoxy-urethane oligomers cured by tertiary amines. Coating on the base of acrylic cyclocarbonates and oligomers with primary amines are similar to conventional polyurethane coatings on the base of acrylic hydroxyl containing oligomers and isocyanates, but mechanical properties and chemical resistance are better.     

Syntheses,characterization, and functionalization of poly(ester amide)s with pendant amine functional groups

Poly(ester amide)s (PEAs) comprising α‐amino acids, diols, and diacids are promising materials for biomedical applications such as tissue engineering and drug delivery because of their tunability and potential for either hydrolytic or enzymatic degradation. Although a number of PEAs of different compositions have been reported, there is a significant need for the incorporation of amino acids with functional side chains. This will allow for the conjugation of drugs or cell signaling molecules in tissue engineering scaffolds, thus expanding the potential applications of these materials. The objective of this work was the incorporation of l ‐lysine into PEAs to provide functionalizable pendant amine groups. Thus, varying percentages of lysine were incorporated into PEAs comprised of l ‐phenylalanine, 1,4‐butanediol, and succinic acid by tuning the ratio of ε‐protected‐l ‐lysine and l ‐phenylalanine derived monomers. The polymers were characterized by nuclear magnetic resonance spectroscopy, infrared spectroscopy, size exclusion chromatography, and differential scanning calorimetry. The lysine ε‐protecting group was removed, then the reactivity of the pendant amines was demonstrated by reaction with amino acid and tri(ethylene glycol) derivatives. The degradation of thin films of polymers were studied using scanning electron microscopy and the incorporation of lysine was found to significantly accelerate both the hydrolytic and enzymatic degradation. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6376–6392, 2008     

New insights into the mechanism of palladium-catalyzed allylic amination

A comparative investigation into palladium-catalyzed allylic amination of unsubstituted aziridines and secondary amines has been carried out. The use of NH aziridines as nucleophiles favors formation of valuable branched products in the case of aliphatic allyl acetates. The regioselectivity of this reaction is opposite to that observed when other amines are used as nucleophiles. Our study provides evidence for the palladium-catalyzed isomerization of the branched (kinetic) product formed with common secondary amines into the thermodynamic (linear) product. In contrast, the branched allyl products obtained from unsubstituted aziridines do not undergo the isomerization process. Crossover experiments indicate that the isomerization of branched allylamines is bimolecular and is catalyzed by Pd(0). The reaction has significant solvent effect, giving the highest branched-to-linear ratios in THF. This finding can be explained by invoking the intermediacy of sigma-complexes, which is consistent with NMR data. The apparent stability of branched allyl aziridines towards palladium-catalyzed isomerization is attributed to a combination of factors that stem from a higher degree of s-character of the aziridine nitrogen compared to other amines. The reaction allows for regio- and enantioselective incorporation of aziridine rings into appropriately functionalized building blocks. The resulting methodology addresses an important issue of forming quaternary carbon centers next to nitrogen. The new insights into the mechanism of palladium-catalyzed allylic amination obtained in this study should facilitate synthesis of complex heterocycles, design of new ligands to control branched-to-linear ratio, as well as absolute stereochemistry of allylamines.     

13-cis-维A酰衍生物合成方法的改进

改进并建立了以4-二甲氨基吡啶(DMAP)-对甲苯磺酸盐为催化剂,二环己基碳酰亚胺(DCC)为缩合剂直接用13-cis-维A酸与醇、酚或胺合成13-cis-维A酰衍生物的方法。合成了8种新目标化合物,收率80%～95%,核磁共振氢谱和碳谱研究表明,13-cis-维A酰部分的构型均保持不变。合成方法彻底抑制了反应中N-异维A酰基脲的副反应,而且反应条件温和,对于极易异构化的13c-is-维A酸的酯化和酰胺化反应十分有利。     

Swelling and hydrolytic degradation of poly(d,l-lactic acid) in aqueous solutions

Low molecular weight poly(lactic acid) was synthesized by direct polycondensation of lactic acid. The oligomers were characterized by viscometry, light scattering, and gel permeation chromatography (GPC). The swelling behaviour of tablets made of the above polymer immersed in buffer solutions at 37 °C was studied. In the same experiments, the hydrolytic stability of d,l-PLA was assessed by measuring the weight loss after drying the tablets. In order to inhibit any degradation due to bacteria, formaldehyde was added in the solution as biostatic factor. The effect of an incorporated drug on the swelling behaviour of d,l-PLA tablets was also considered. It was found that the incorporation of drug in d,l-PLA tablets increases their swelling index, probably due to the creation of additional porosity in the specimens or other interaction between drug and polymeric matrix.     

N-Vinylformamide – Building Block for Novel Polymer Structures

Abstract

N-Vinylformamide (NVF, N-ethenylformamide) is a precursor to amide and amine functional polymers and to other monomers, oligomers, and functional polymers. NVF shows attractive physical and toxicological properties and high reactivity, both in polymerization and in subsequent hydrolysis to cationic and reactive amine functional polymers or oligomers. NVF radical polymerization readily yields water soluble homopolymers with molecular weights from 10⁴ to >10⁶. Copolymerizability is similar to other vinyl amides. Unexpectedly, NVF will also undergo cationic oligomerization. Hydrolysis of polymers and copolymers with base or acid is facile, although reactions with neighboring groups (e.g., with coacrylate ester groups to give lactams) complicate copolymer hydrolysis.

Reaction of NVF at the unusually acidic NH group allows reaction with isocyanates to give vinylacylureas or Michael addition to acrylates to give a family of new N-vinylformamidopropionate esters. These esters in turn react with functional amines to generate new families of divinyl, vinyl/alcohol functional, or vinyl/amino functional comonomers. Applications for NVF and its derived monomers and polymers appear numerous, in particular in radiation cure coatings, based on their good physical and toxicological properties.     

Solid phase synthesis of aromatic oligoamides: application to helical water-soluble foldamers

Synthetic helical aromatic amide foldamers and in particular those based on quinolines have recently attracted much interest due to their capacity to adopt bioinspired folded conformations that are highly stable and predictable. Additionally, the introduction of water-solubilizing side chains has allowed to evidence promising biological activities. It has also created the need for methods that may allow the parallel synthesis and screening of oligomers. Here, we describe the application of solid phase synthesis to speed up oligomer preparation and allow the introduction of various side chains. The synthesis of quinoline-based monomers bearing protected side chains is described along with conditions for activation, coupling, and deprotection on solid phase, followed by resin cleavage, side-chain deprotection, and HPLC purification. Oligomers having up to 8 units were thus synthesized. We found that solid phase synthesis is notably improved upon reducing resin loading and by applying microwave irradiation. We also demonstrate that the introduction of monomers bearing benzylic amines such as 6-aminomethyl-2-pyridinecarboxylic acid within the sequences of oligoquinolines make it possible to achieve couplings using a standard peptide coupling agent and constitute an interesting alternative to the use of acid chloride activation required by quinoline residues. The synthesis of a tetradecameric sequence was thus smoothly carried out. NMR solution structural studies show that these alternate aminomethyl-pyridine residues do not perturb the canonical helix folding of quinoline monomers in protic solvents, contrary to what was previously observed in nonprotic solvents.     

Hairpin folding behavior of mixed α/β-peptides in aqueous solution

The invention of new strategies for the design of protein-mimetic oligomers that manifest the folding encoded in natural amino acid sequences is a significant challenge. In contrast to the α-helix, mimicry of protein β-sheets is less understood. We report here the aqueous folding behavior of a prototype α-peptide hairpin model sequence varied at cross-strand positions by incorporation of 16 different β-amino acid monomers. Our results provide a folding propensity scale for β-residues in a protein β-sheet context as well as high-resolution structures of several mixed-backbone α/β-peptide hairpins in water.     

A General Method for N‐Methylation of Amines and Nitro Compounds with Dimethylsulfoxide

DMSO methylates a broad range of amines in the presence of formic acid, providing a novel, green and practical method for amine methylation. The protocol also allows the one‐pot transformation of aromatic nitro compounds into dimethylated amines in the presence of a simple iron catalyst.     

p-Phenyleneethynylene-based comb-like oligomers: the synthesis and self-assembling property

This paper describes the self-assembling property of three series of p-phenyleneethynylene based comb-like oligomers, which carry multiple peripheral side chains of different polarity. The new oligomers are prepared readily through the formation of the hydrazone bonds from the corresponding aldehyde and gallic acid-derived benzohydrazides. In polar solvents such as methanol and ethanol, the oligomers that bear n-decyl or 2-(2-(dioctylamino)-2-oxoethyl-amino)-2-oxoethoxyl unit (DOAOE) segments as the side chains are revealed to form vesicular structures, while the oligomers carrying hydrophilic oligo(ethyleneglycol) side chains do not. The structures of the vesicles are evidenced by SEM, AFM, TEM, and dye-encapsulation experiments. UV–vis absorption spectroscopic experiments suggest that the vesicles are generated through the stacking of the conjugated backbones, which is promoted by the solvophobic interaction of the peripheral side chains.     

Green chemistry of polyurethanes

The current state and the main problems in a new field of macromolecular compounds—green chemistry of polyurethanes—based on cyclocarbonate reactions with amines, including those with cyclocarbonate-containing oligomers from renewable vegetable raw material, are briefly discussed.     

Asymmetric synthesis of anti-1,2-amino alcohols via the Borono-Mannich reaction: a formal synthesis of (-)-swainsonine

Chiral alpha-hydroxy aldehydes generated in situ by the ADH reaction of vinyl sulfones undergo a borono-Mannich reaction with beta-styrenyl boronic acid and primary amines to give anti-1,2-amino alcohols in high enantiomeric purities (83-95% ee). This new method allows much more rapid access to these valuable chiral building blocks that has been used in a short formal synthesis (10 synthetic steps from 4-penten-1-ol) of (-)-swainsonine.