Benzylamino Group Research Articles

Photosynthetic electron transport inhibition by 2-substituted 4-alkyl-6-benzylamino-1,3,5-triazines with thylakoids from wild-type and atrazine-resistant Chenopodium album.

The effect of 2-benzylamino-1,3,5-triazines on photosynthetic electron transport (PET) was measured with thylakoids isolated from atrazine-resistant, wild-type Chenopodium album, and spinach to find novel 1,3,5-triazine herbicides bearing a strong PET inhibition. The PET inhibition assay with Chenopodium (wild-type and resistant), yielded a resistance ratio (R/W = I50 (resistant)/I50 (wild-type)) of 324 for atrazine while for benzylamino-1,3,5-triazine derivatives of diamino-1,3,5-triazines a R/W of 11 to 160 was found. The compounds having a benzylamino group at one of the amino groups in the diamino-1,3,5-triazines have a resistant ratio down to one half to 1/30 of the atrazine value. The average resistance ratio of 21 benzylamino derivatives of monoamino-1,3,5-triazines was found to be about 4.0. The inhibition of 21 benzylamino-1,3,5-triazines assayed with atrazine-resistant Chenopodium thylakoids, indicated by pI50 (R)-values, correlated well with the PET inhibition pI50 (W) of wild-type thylakoids from Chenopodium.

Dynamics and Binding Modes of Free cdk2 and its Two Complexes with Inhibitors Studied by Computer Simulations

This article presents a molecular dynamics (MD) study of the cdk2 enzyme and its two complexes with the inhibitors isopentenyladenine and roscovitine using the Cornell et al. force field from the AMBER software package. The results show that inserting an inhibitor into the enzyme active site does not considerably change enzyme structure but it seemingly changes the distribution of internal motions. The inhibitor causes differences in the domain motions in free cdk2 and in its complexes. It was found out that repulsion of roscovitine N9 substituent causes conformational change on Lys 33 side chain. Isopentenyladenine forms with Lys 33 side chain terminal amino group a hydrogen bond. It implies that the cavity, where N9 substituent of roscovitine is buried, can adopt larger substituent due to Lys 33 side chain flexibility. The composition of electrostatic and van der Waals interactions between the inhibitor and the enzyme were also calculated along both cdk2/inhibitor MD trajectories together with MM-PB/GBSA analysis. These results show that isopentenyladenine-like inhibitors could be more effective after modifications leading to an increase in their van der Waals contact with the enzyme. We suggest that a way leading to better inhibitors occupying isopentenyladenine binding mode could be: to keep N9 and N7 purine positions free, to keep 3,3-dimethylallylamino group at C6 position, and to add, e.g., benzylamino group at C2 position. The results support the idea that the isopentenyladenine binding mode can be used for cdk2 inhibitors design and that all possibilities to improve this binding mode were not uncovered yet.

The complexation of peptides by aminocyclodextrins

AbstractFour β‐cyclodextrins (CDs) were prepared bearing either an (N,N‐dimethylamino)propylamino group (1), an (N‐methyl)‐piperazino group (2) or a benzylamino group (3), or seven methylamino susbtituents (4). Association constants K in water with di‐ and tripeptides reach up to 200 M −1, and after protection at the N‐terminus up to 680 M −1. Appreciable binding occurs only in the presence of lipophilic amino acid side‐chains, with preference for this at the C‐terminus. A moderate sequence and side‐chain selectivity is observed with 1, 2 and 3, but less so with the highly charged 4 where ion pairing dominates. Detailed NMR analyses with advanced techniques including T‐ROESY and GHSQC allow full assigment of most 1H and 13C signals, with extraction of many substituent and complexation induced shifts changes (SIS and CIS values, respectively). The CIS values and NOE cross peaks from ROESY experiments provide for insight into the binding modes of selected complexes, indicating, e.g., the simultaneous presence of complexes with a peptide phenyl unit approaching from both the narrow and the wide side of the CD cavity. With 3 one observes self‐inclusion of the pendant phenyl ring within the cavity, and its replacement by analytes such as peptides, or by adamantanecarboxylic acid. The inclusion modes are illustrated with force field simulated structures and many NMR spectra, which are made available in electronic supplements. Copyright © 2001 John Wiley & Sons, Ltd. Additional material for this paper is available from the epoc website at http://www.wiley.com/epoc: (NMR shift tables; 3D coordinates for molecular structures; 1D‐ and 2D‐NMR spectra)

Synthesis of the Novel Amino Acid 4-Amino-3-(aminomethyl)benzoic Acid (AmAbz) and Its Protected Derivatives as Building Blocks for Pseudopeptide Synthesis

4-Amino-3-(aminomethyl)benzoic acid (1) (AmAbz) is a novel unnatural amino acid with promise in applications as a building block for the synthesis of peptidomimetics and as a scaffold for combinatorial chemistry. It was efficiently synthesized in three steps (63% overall yield) from 4-aminobenzoic acid, by means of regioselective amidomethylation with hydroxymethylphthalimide. AmAbz (1) contains three distinct functionalities which could be discriminated from one another. Firstly, Boc2O or Fmoc−OSu reacted selectively with the benzylamino group to give the monoprotected derivatives AmAbz(Boc) (8a) or AmAbz(Fmoc) (8b), respectively. The absence of acylation at the arylamino group was also noticed in coupling experiments using the BOP reagent and building block 8b. This made protection of the arylamino group unnecessary either for peptide bond formation at the carboxyl group, or for subsequent elongation of a peptide chain at the benzylamino group. Finally, the arylamino group could be acylated under base-free, carbodiimide-mediated coupling conditions. These properties are illustrated by the solid-phase synthesis of the AmAbz-containing branched pseudopeptide Fmoc−Ala−Phe−AmAbz(H−Lys−Leu)−Val−Gly−NH2 (15). The synthesis of Fmoc−AmAbz(Boc) (10) is also described.

Comparison of the two anomers of methyl 2-(N-benzylamino)-2, 3-dideoxy-4,6-O-phenylmethylene-3-C-phenylsulfonyl-D-glucopyranoside

The title compounds, the alpha and beta anomers of methyl 2-(N-benzylamino)-2,3-dideoxy-4, 6-O-phenylmethylene-3-C-phenylsulfonyl-D-glucopyranoside, C(27)H(29)NO(6)S, belong to the class of deoxyamino-sugars prepared by the addition of amines at C2. The endocyclic bond lengths of the pyranose ring in the alpha anomer are shorter than the corresponding bonds in the beta anomer. The pyranose ring is in the chair form in the former, while it is in the boat form in the latter. These observed differences could be attributed to the C2 substitution of a bulky group. The phenylsulfonyl and benzylamino groups are in equatorial positions in the alpha anomer, while the benzylamino group is axial in the beta anomer.

Darstellung chiraler heterocyclischer β-Aminosäureester / Preparation of Chiral Heterocyclic Esters of β-Amino Acids

Chiral β-amino alcohols were successively prone to N-benzylation, O-allylation and oxidation of the resulting benzylamino group to give nitrones 3 which on hydrolysis afforded chiral hydroxylamines HO-NH-CH(R)-CH2-O-CH2-CH=CH2 ((S)-4: R = Me, Bn, iPr. (R)-4: R = Et). Swern oxidation of methyl 2,2-dimethyl-3-hydroxypropionate (16) and treatment of the resulting aldehyde 17 with hydroxylamines (S)-4b (R = Bn) or (R)-4d (R = Et) provided nitrones 18 that underwent an intramolecular 1,3-dipolar cycloaddition on heating yielding the bicyclic β-amino-acid esters 19b and ent-19d, respectively.Reductive cleavage of the N,0- bond of compounds 19 afforded the eight-membered ring compounds 20b and ent-20d, respectively. N-Benzylalaninol (22) was treated with /3-bromo-methacrylate to give the amino alcohol 23. Swern oxidation and subsequent treatment with N-ferf-butylhydroxylamine provided the bicyclic ester 26a (R = t-Bu) via the corresponding nitrone 24. Oxime 25 was prepared in an analogous way as 24 with unsubstituted hydroxylamine. It underwent an intramolecular 1.3- dipolar cycloaddition yielding 26b on heating in toluene. Reduction of 26a afforded the pyrrolidine-carboxylic ester 27a.

Synthesis and Bactericidal Characteristics of N-Alkyl-2-benzylaminopyridinium lodides.

N-Alkyl-2-benzylaminopyridinium iodides (2BAP-n) were synthesized from 2-benzylaminopyridine and n-alkyl iodide (alkyl group: hexyl, octyl, decyl, dodecyl, tetradecyl, hexadecyl and octadecyl) at 80°C under 80MPa of static pressure, and their bactericidal characteristics were investigated with respect to their chemical structure and physicochemical properties. 2BAP-12 exhibited a wide and high range of bactericidal activity, and a higher activity than N-dodecylpyridinium iodide (P-12), which has only an alkyl group as a substituent on the pyridine ring, against all bacteria tested. The bactericidal activity of 2BAP-n against Escherichia coil K12 W3110 was affected by the carbon number of the alkyl chain. The plot of the activity of 2BAP-n against molecular hydrophobicity was found to be parabolic. From the result, it was suggested that the activity of 2BAP-n is dependent on the molecular hydrophobicity. Similarly, the activity had a linear dependence on the hydrophobicity of cell surfaces. The activity increased with an increase in the hydrophobicity, as well as in the case of general QACs. 2BAP-12 maintained high activity in the pH range from 5 to 8.5, though the activity was lower than that of P-12 in alkaline solution. It was thought that this exceptional bactericidal property is due to the effect of a large substituent, the benzylamino group, introduced onto the pyridine ring.

Preparation of resins containing phenol derivatives from chloromethylstyrene‐tetraethyleneglycol dimethacrylate copolymer beads and antibacterial activity of resins

Copolymer beads (RCCS-4G) with many chloromethyl groups were prepared by treating macroreticular chloromethylstyrene-tetraethyleneglycol dimethacrylate (4G) copolymer beads with chloromethylether. Copolymer beads (RAAS-4G) with benzylamino groups were prepared by treating RCCS-4G with potassium phthalimide. Then the copolymer beads containing phenol derivatives were prepared by treating RAAS-4G with p-hydroxybenzoic acid (pHBA), 2,4-dihydroxybenzoic acid (DHBA), and 3,4,5-trihydroxybenzoic acid (gallic acid, GA) in N,N-dimethylformamide. The antibacterial activity of the obtained resins was examined against Escherichia coli and Staphylococcus aureus. Resins containing phenolic hydroxy groups of 2.3–7.7 mequiv/g were obtained. Antibacterial activity of the resins containing various phenol derivatives against E. coli or S. aureus increased in the order of RAAS-4G-GA > RAAS-4G-DHBA > RAAS-4G-pHBA. The resins containing phenol derivatives exhibited higher antibacterial activity against E. coli than against S. aureus and high activity even against bacteria in NaCl solution. Scanning electron micrographs showed that high antibacterial activity was brought about by the phenolic hydroxyl groups in the resin. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 1621–1630, 1997

Preparation of resins containing phenol derivatives from chloromethylstyrene-tetraethyleneglycol dimethacrylate copolymer beads and antibacterial activity of resins

Copolymer beads (RCCS-4G) with many chloromethyl groups were prepared by treating macroreticular chloromethylstyrene-tetraethyleneglycol dimethacrylate (4G) copolymer beads with chloromethylether. Copolymer beads (RAAS-4G) with benzylamino groups were prepared by treating RCCS-4G with potassium phthalimide. Then the copolymer beads containing phenol derivatives were prepared by treating RAAS-4G with p-hydroxybenzoic acid (pHBA), 2,4-dihydroxybenzoic acid (DHBA), and 3,4,5-trihydroxybenzoic acid (gallic acid, GA) in N,N-dimethylformamide. The antibacterial activity of the obtained resins was examined against Escherichia coli and Staphylococcus aureus. Resins containing phenolic hydroxy groups of 2.3–7.7 mequiv/g were obtained. Antibacterial activity of the resins containing various phenol derivatives against E. coli or S. aureus increased in the order of RAAS-4G-GA > RAAS-4G-DHBA > RAAS-4G-pHBA. The resins containing phenol derivatives exhibited higher antibacterial activity against E. coli than against S. aureus and high activity even against bacteria in NaCl solution. Scanning electron micrographs showed that high antibacterial activity was brought about by the phenolic hydroxyl groups in the resin. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 1621–1630, 1997

Synthesis of chiral and achiral analogues of ambroxol via palladium-catalysed reactions

Chiral cis- and trans-4-aminocyclohex-2-enols and achiral 4-aminocyclohexanols, which all are analogues of ambroxol, are prepared via stereoselective allylic substitution of cyclohex-2-ene-1,4-diol derivatives or 1-acetoxy-4-chlorocyclohex-2-ene. The chiral target molecules are obtained in enantiomerically pure form by employing a previously described enantiodivergent synthesis of cis- and trans-4-aminocyclohex-2-enols. It has been found that bis(amine) nucleophiles 7a and 7b react only at the benzylic amino group under the conditions employed.

Direct Observation of Orthogonal Orientation of an Aromatic Ring Attached to the Carbene Carbon in Fischer Carbene Complexes in Solution: Diastereotopicity of Benzyl Protons as a Stereochemical Probe

Diastereotopicity of methylene protons of benzyloxy and benzylamino groups in Fischer carbene complexes serves as a stereochemical probe to reveal orthogonal orientation of the aromatic rings attached to the carbene carbon with respect to the metal−carbene π-plane in solution.

Kondensierte 1.2‐Dithiole, I. Synthese von Thiolutin und verwandten Verbindungen

Ring‐Fused 1,2‐Dithioles, I. — Synthesis of Thiolutine and Related CompoundsThe 1,2‐dithiolopyrrole 1 (thiolutine) has been obtained on two different routes. Firstly, by synthesis of the dithiolopyrrole 6a and introduction of the acetamino function into compound 6d by nitration followed by ester saponification and decarboxylation. 6d is also available from 9k by oxidative ring contraction which occurs with simultaneous dealkylation of the benzylamino group. Secondly, by synthesis of the dithiinopyrrole 15b and introduction of the acetamino function into compound 15g by Beckmann rearrangement followed by ring contraction.

Nucleocyclitols. Synthesis of substituted purinyl-muco-inositol derivatives

Several carbocyclic nucleoside analogs possessing a 6-substituted purine linked to a mesylated muco-inositol were synthesized. The coupling of triethylamine-activated 6-chloropurine with 2,3-anhydro-l,5,6-tri-O-(methanesulfonyl)-epi-inositol gave a 6-chloro purinyl muco-inositol amenable to further synthetic transformations in the heterocyclic moiety by substitution of the chlorine atom by nitrogen nucleophiles such as methylamino, diethylamino, benzylamino, hydrazino, morpholino, hydroxylamino, piperidino, and glycyl groups.

Central Cholinergic Agents. I. Potent Acethlcholinesterase Inhibitors, 2-(.OMEGA.-(N-Alkyl-N-(.OMEGA.-phenyl-alkyl)amino)alkyl)-1H-isoindole-1,3(2H)-diones, Based on a New Hypothesis of the Enzyme's Active Site.

It has been suggested that the active site of acetylcholinesterase contains a hydrophobic binding site (HBS-1), which is closely adjacent to both the anionic and the esteratic sites. In this paper, we assumed that there exists another hydrophobic binding site (HBS-2), some distance removed from the anionic site. On this assumption, a new working hypothesis was proposed for the design of acetylcholinesterase inhibitors. A series of 2-[omega-[N-alkyl-N-(omega-phenyl-alkyl)amino]alkyl]-1H- isoindole-1,3(2H)-diones was designed based on this hypothesis and tested for its inhibitory activities on acetylcholinesterase. Some in this series were revealed to be more potent than physostigmine. Optimum activity was found to be associated with a five carbon chain length separating the benzylamino group from the 1H-isoindole-1,3(2H)-dione (phthalimide) moiety. Quantitative study of substitution effect on the phthalimide moiety revealed that hydrophilic and electron-withdrawing groups enhance the activity.

ChemInform Abstract: INHIBITION OF UPTAKE OF CATECHOLAMINES BY BENZYLAMINE DERIVATIVES

AbstractAus den Benzylalkoholen (I) werden über die Benzylchloride (II) die Aminoalkohole (IV) hergestellt, die mit Thionylchlorid in die Chlorethylderivate (V) übergeführt werden.

Inhibition of uptake of catecholamines by benzylamine derivatives

Eight benzylamine analogues of bretylium were synthesized, including N-(2-chloroethyl)-N-ethyl-2-methylbenzylamine (5), and evaluated as inhibitors of accumulation of norepinephrine and dopamine in rat brain homogenates. All compounds gave an I50 value (concentration of inhibitor that causes 50% reduction in control accumulation) considerably lower against norepinephrine in cortex that against dopamine in striatum. High potency (low I50) and high specificity (preference for inhibition of norepinephrine transport compared to dopamine transport) are associated with a (2-chloroethyl) moiety, tertiary amino center, and ortho substitution of the aromatic function in the benzylamino group. 5 also inhibited the uptake of norepinephrine in rabbit aorta, indicating its effect against the uptake process in general. Cocaine protects against the effects of 5 in coincubation studies when compared to the appropriate controls, indicating that 5 acts at or close to the site of action of cocaine which is thought to be the uptake carrier site.

1,2-Dihydroquinolines: preparation and isolation as intermediates in the synthesis of quinolines

2,6-Dimethyl-1,2-dihydroquinoline has been isolated as an intermediate in the Doebner-Miller synthesis of 2,6-dimethylquinoline. Dihydroquinolines may be efficiently prepared by the acid catalysed elimination of water from a 4-hydroxy-1,2,3,4-tetrahydroquinoline. The analogous 4-phenylamino derivatives also undergo facile elimination of the benzylic amino group under similar conditions.

ChemInform Abstract: MECHANISM AND STEREOCHEMISTRY OF THE HYDROLYSIS OF 4‐ARYLAMINO‐1,2,3,4‐TETRAHYDROQUINALDINES

Rates of acid-catalyzed hydrolysis of the benzylic amino group in stereoisomers of 4-arylamino-1,2,3,4-tetrahydroquinaldines have been determined by n.m.r. spectroscopy. Those isomers which have a pseudo-axial leaving group react more rapidly than those with a pseudo-equatorial leaving group, forming in each case the isomer with a pseudo-axial hydroxyl group as the kinetically controlled product. This product is converted in time to an equilibrium mixture of the two stereoisomeric alcohols. The reaction is inhibited by excess acid and appears to proceed through an intermediate carbonium ion which is stabilized by the heterocyclic nitrogen atom.

Mechanism and Stereochemistry of the Hydrolysis of 4-Arylamino-1,2,3,4- tetrahydroquinaldines

Rates of acid-catalyzed hydrolysis of the benzylic amino group in stereoisomers of 4-arylamino-1,2,3,4-tetrahydroquinaldines have been determined by n.m.r. spectroscopy. Those isomers which have a pseudo-axial leaving group react more rapidly than those with a pseudo-equatorial leaving group, forming in each case the isomer with a pseudo-axial hydroxyl group as the kinetically controlled product. This product is converted in time to an equilibrium mixture of the two stereoisomeric alcohols. The reaction is inhibited by excess acid and appears to proceed through an intermediate carbonium ion which is stabilized by the heterocyclic nitrogen atom.

Syntheses of analgesics. 28. Syntheses of 4-amino-3-methyl-1,2-diphenyl-2-propionyloxybutane derivatives

In order to obtain an effective analgesic agent, 4-amino-3-methyl-1, 2-diphenylbutane derivatives were synthesized. These compounds, the structure of which are similar to propoxyphene, have hydroxyl, methoxyl, benzyloxyl, or acyloxy group in the benzene ring and dimethylamino, 1-piperidino, diallylamino, or benzylamino group as a basic function. Further, two kinds of diastereoisomers were separated by column chromatography or fractional crystallization. Structure of these compounds was confirmed by spectral data.