Synthesis, Characterization and the Effect of Glucose-lowering of Guanidino Acid Oxovanadium（Ⅳ） Complexes

Two guanidino acid oxovanadium(Ⅳ) complexes have been synthesized. Preliminary tests in vivo have shown that the two title complexes all display lowering glucose activity in vivo to STZ-rats. The effect of glucose-lowering of guanidino acetic acid oxovanadium(Ⅳ) complex in vivo is higher than that of guanidino propanoic acid oxovanadium(Ⅳ) complex.     

Design,synthesis and application of new bile acid ligands with 1,2,3-triazole ring

New dimers have been obtained from propargyl ester of bile acids and α,α′-diazide-m-xylene by intermolecular 1,3-dipolar cycloaddition. These compounds have been used as ligands to form intermolecular hydrogen bonds with various aromatic acids. The structures of all products were confirmed by spectroscopic (¹H NMR, ¹³C NMR and FT-IR) analysis, mass spectrometry (ESI, MALDI) and PM5 semiempirical methods.     

3-Amino-2H-Azirines. Synthons for α,α-Disubstituted α-Amino Acids in Heterocycle and Peptide Synthesis [New Analytical Methods (43)]

The recent upswing in peptide chemistry has been accompanied by an increasing interest in nonproteinogenic amino acids. These include the α,α-disubstituted glycines, the best known of which is Aib (2-aminoisobutyric acid, 2-methylalanine). These α-amino acids occur in natural oligopeptides such as the peptaibols, a class of membrane-active ionophores that has been isolated from fungal cultures. The twofold substitution at the α-C atom of the amino acids severely restricts the conformational freedom of the peptides and causes particular secondary structures to be favored; thus, α, α-disubstituted α-amino acids induce the formation of β turns or helices. 3-Amino-2H-azirines are ideal synthons for the construction of oligopeptides, cyclic peptides and depsipeptides (peptolides) containing such α,α-disubstituted α-amino acids. The presence of the ring strain in these molecules means that they can be used in peptide coupling without the need for additional activating reagents. Using 3-amino-2H-azirines a large array of heterocycles containing α, α-disubstituted α-amino acids as structural elements within their skeleton can be synthesized. The driving force in these reactions is the release of the strain on the three-membered ring, which usually takes place in a ring-expansion reaction. The mechanistic elucidation of these reactions, which can be quite complex, contains some surprises.     

Carbon-13 n.m.r. spectra of branched carboxylic acids and their derivatives

¹³C n.m.r. spectra have been measured for 39 compounds with branched structures including carboxylic acids, their methyl and ethyl esters, nitriles and chlorinated esters. The results obtained indicate that the ¹³ C n.m.r. technique is applicable to structure assignment of acids and their derivatives containing various numbers of substituents on the chain. The dependence of the carboxylic carbon chemical shift on the number and structure of α-positioned substituents has been determined. Calculation of the chemical shifts for branched carboxylic acids, esters and nitriles from the corresponding increments using the additivity scheme is shown to be possible in principle.     

Improved high-performance liquid chromatographic determination of guanidino compounds by precolumn dervatization with ninhydrin and fluorescence detection

Ninhydrin has been investigated as a pre-column derivatization reagent for guanidino compounds. The reaction takes place under strongly alkaline conditions, followed by a second step at low pH and elevated temperature. This procedure yields derivatives with favourable fluorescence properties (excitation at 390 nm, emission at 470 nm). Amino acids do not react with ninhydrin under these conditions so that the method can easily be used for biological samples. Reversed-phase HPLC separations of the derivatives of several representative guanidino compounds in human blood have been achieved with gradients consisting of aqueous formic acid and methanol. Fluorescence detection yields quantification limits of about 20 microg L(-1). Hyphenation with electrospray mass spectrometry has been used to confirm the identity of the derivatives.     

Halichondria sulfonic acid, a new HIV-1 inhibitory guanidino-sulfonic acid, and halistanol sulfate isolated from the marine sponge Halichondria rugosa Ridley & Dendy

A new sulfur-containing guanidino derivative, halichondria sulfonic acid (1) showing anti-HIV-1 activity, and halistanol trisulfate (2) with anti-tumor activity have been isolated from the marine sponge Halichondria rugosa Ridley & Dendy collected in the Chinese Southern Sea. The structure of 1 was elucidated by analysis of spectroscopic and crystal data.     

Radiation-induced destruction of hydroxyl-containing amino acids and dipeptides

The yields of molecular products resulting from radiolysis of hydroxyl-containing amino acids and dipeptides under various conditions were determined. The possibility of a new radiation-induced destruction pathway has been shown for serine and threonine, as well as for the dipeptides having residues of these amino acids at the N-terminal part of the respective molecule. This process includes formation of N-centered radicals from the starting molecules followed by their decomposition with elimination of side substituents. On radiolysis, serine and threonine were also shown to undergo free-radical destruction to form acetaldehyde and acetone, respectively. A mechanism has been proposed including consecutive stages of fragmentation of α-hydroxyl-containing carbon-centered radicals with elimination of ammonia and decomposition of the secondary radicals with elimination of CO₂. The yields of CO₂ obtained on radiolysis of serine and threonine were significantly higher (except for solutions at pH 12) than those for alanine and valine, which have no hydroxyl groups in their structures. The obtained data indicate that the hydroxyl-containing amino acids occupy a special place among other amino acids as regards the variety of radiation-induced reactions which they may undergo due to their structural features.     

Optical rotatory dispersion and circular dichroism. LXXV. Circular dichroism of some aryl-amino acids

CD. curves have been recorded for α-aryl-α-amino acids, esters and amides related to α-phenylglycine, α-phenyl-alanine and their N-dimethyl derivatives, and for the corresponding α-cyclohexyl-α-amino acids and esters. Compounds with the (S)-configuration at the single asymmetric carbon atom give strong positive Cotton effects near 220 nm. The conformations of the acids are discussed and compared with those of other α-amino acids.     

Synthesis and conformational properties of model dipeptides containing novel axially chiral α,β-didehydroamino acids at the (i+1) position of a β-turn conformation

A series of model dipeptides containing some novel axially chiral α,β-didehydroamino acids at the (i+1) position has been synthesised by reaction of the corresponding 4-(4-alkylcyclohexylidene)-2-phenyl-1,3-oxazol-5(4H)-one with (S)-phenylalanine cyclohexylamide. The conformations of two dipeptides in the crystal state have been studied by X-ray diffraction crystallographic analysis. The backbone torsion angles suggest that both peptides adopt similar type-II′ β-turn conformations. NMR spectroscopy has revealed that relatively rigid β-turn structures also persist in solution and that the absolute configurations of the axially chiral α,β-didehydroamino acids do not significantly influence the conformation of the peptide chain. Both heterochiral and homochiral dipeptides are found to accommodate the same βII′-turn conformation. Axially chiral α,β-didehydroamino acids (R_a)- and (S_a)-4-methyl-, 4-phenyl- and (4-tert-butylcyclohexylidene)glycine can be considered as elongated structural analogues of alanine, phenylglycine and tert-leucine of R and S configuration since, in these chiral α,β-didehydroamino acids, the methyl, phenyl and tert-butyl groups are located about 4.3 Å away from the peptide backbone in which they are incorporated.     

Synthesis of a new heterocyclic ring system 2,3,5,6,7,9,10,11-octahydro-lH-cyclopenta[9,H)]benzo[i,j] quinolizine-1,9-dione

Reaction of 1,2,3,4-tetrahydroquinoline (1) with different α,β-unsaturated acids in the presence of PPA has been investigated. With acrylic acid, 1 affords two compounds identified as 1-keto-benzo[i,j]quinolizine (III) and 2,3,5,6,7,9,10,1 1-octahy dro-1H-cy el open ta [9,10] benzo [i,j]-quinolizine-1,9-dione (IV). A similar reaction of 1 with a-methyl acrylic and crotonie acids gives compounds V and VI whose structures are analogous to that of IV. These were deduced from their spectral and analytical data.     

Structural Investigation of Hybrid Peptide Foldamers Composed of α-Dipeptide Equivalent β-Oxy-δ5-amino Acids

Due to their equivalent lengths, δ-amino acids can serve as surrogates of α-dipeptides. However, δ-amino acids with proteinogenic side chains have not been well studied because of synthetic difficulties and because of their insolubility in organic solvents. Recently we reported the spontaneous supramolecular gelation of δ-peptides composed of β(O)-δ⁵-amino acids. Here, we report the incorporation of β(O)-δ⁵-amino acids as guests into the host α-helix, α,γ-hybrid peptide 12-helix and their single-crystal conformations. In addition, we studied the solution conformations of hybrid peptides composed of 1:1 alternating α and β(O)-δ⁵-amino acids. In contrast to the control α-helix structures, the crystal structure of peptides with β(O)-δ⁵-amino acids exhibit α-helical conformations consisting of both 13- and 10-membered H-bonds. The α,δ-hybrid peptide adopted mixed 13/11-helix conformation in solution with alternating H-bond directionality. Crystal-structure analysis revealed that the α,γ⁴-hybrid peptide accommodated the guest β(O)-δ⁵-amino acid without significant deviation to the overall helix folding. The results reported here emphasize that β(O)-δ⁵-amino acids with proteinogenic side chains can be accommodated into regular α-helix or 12-helix as guests without much deviation of the overall helix folding of the peptides.     

GC-MS analysis of metabolites from soxhlet extraction,ultrasound-assisted extraction and supercritical fluid extraction of Salacca zalacca flesh and its alpha-glucosidase inhibitory activity

Abstract

Different extraction processes were employed to extract bioactive metabolites from Salacca zalacca flesh by a range of aqueous and organic solvents. The highest extraction yield was obtained by 50% ethanol extract of SE (73.18?±?4.35%), whereas SFE_1 showed the lowest yield (0.42?±?0.08%). All extracts were evaluated for in vitro α-glucosidase inhibitory activity, measured by their IC₅₀ values in comparison to that of quercetin, the positive control (IC₅₀ = 2.7?±?0.7?μg/mL). The lowest α-glucosidase inhibitory activity was indicated by water extract of SE (IC₅₀ = 724.3?±?42.9?μg/mL) and the highest activity was demonstrated by 60% ethanol extract by UAE (IC₅₀ = 16.2?±?2.4?μg/mL). All extracts were analysed by GC-MS and identified metabolites like carbohydrates, fatty acids, organic acids, phenolic acids, sterols and alkane-based compounds etcetera that may possess the potential as α-glucosidase inhibitor and may attribute to the α-glucosidase inhibitory activity.     

Some new protocols for the assignment of absolute configuration by NMR spectroscopy using chiral solvating agents and CDAs

The utility of enantiopure BINOL (1,10-Bi-2-naphthol), in a ternary ion-pair complex, which is obtained using a carboxylic acid and an organic base, as a versatile chiral solvating agent (CSA) has been demonstrated for chiral analysis and the absolute configuration assignment of hydroxy acids. Another protocol where the utility of NOBIN as a CSA has been developed for discrimination and absolute configuration assignment of acids, hydroxy acids and their derivatives with a distinct strategy where a third ingredient, p-toluenesulfonic acid (p-TsOH) serves as a linker. In addition some three component chiral derivatization protocols have been introduced, such as the use of 2-formylphenylboronic acid and enantiopure mandelic acid or a primary amine for the determination of the configuration of primary amines and hydroxy acids, respectively. A simple, rapid and highly efficient three component chiral derivatizing protocol has also been discussed which was developed for assigning the absolute configuration of chiral α-hydroxy acids and their derivatives, which involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and (S)-[1,1-binaphthalene]-2,2-diamine separately. In a few examples, the DFT based theoretical calculations have been carried out to determine the geometry optimized structures of the complexes.     

MALDI-MS analysis of sialylated N-glycan linkage isomers using solid-phase two step derivatization method

Sialic acids usually locate at the terminal of many glycan structures in either α(2,3) or α(2,6) linkage, playing different roles in various biological and pathological processes. Several linkage specific carboxyl derivatization methods have been reported to discriminate between α(2,3) and α(2,6)-linked sialic acids by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Among them, ethyl esterification was recently reported to achieve linkage specific derivatization between α(2,3) and α(2,6)-linked sialic acids with good selectivity. However, the method suffered from the instability of the generated lactones and byproducts of the derivatives. To overcome these shortcomings, a solid-phase two step derivatization method was introduced to convert the α(2,6)-linked sialic acid into ethyl esters and the α(2,3)-inked counterparts into N-methyl amides, respectively. Under the optimized derivatization conditions, our method was able to achieve accurate relative quantification of N-glycan as well as their corresponding sialylated linkage types, superior to the ethyl esterification method. The solid phase derivatization strategy was further applied to investigate N-glycans from biosimilar antibody drug and human serum from patients and healthy volunteers. This method has the potential to be used in the biomarker discovery and pharmaceutical industry.     

The synthesis of novel phosphonodipeptides and their herbicidal activity

A series of novel phosphonodipeptides has been synthesized from diphenyl α-aminoalkylphosphonates and N-chloroacetyl-N-alkyl (or aryl)glycine ethyl esters. The structures of all the compounds prepared were proved by ¹H NMR, IR, MS, and elemental analyses. The bioassay tests showed that some of the compound have good herbicidal activity.     

N-(polyfluoroaryl)-hydroxylamines. Synthesis and properties

Fluorine-containing N-arylhydroxylamines have been obtained by the action of hydroxylamine or its N- and O-derivatives on polyfluorinated benzenes and pentafluoropyridine. The influence of fluorine atoms on the reactivity of hydroxylamino group has been investigated. The reaction of N-polyfluoroarylhydroxylamines with aldehydes has been shown not to occur, whereas their reaction with nitrosobenzenes leads to azoxybenzenes and with Lewis acids leads to corresponding nitrosobenzenes, azoxybenzenes and anilines. The action of acids on 2,3,5,6-tetrafluorophenylhydroxylamine leads to the acid-catalyzed rearrangement of the latter into 4-amino-2,3,5,6-tetrafluorophenol. C,N-Diarylnitrones have been obtained by the oxidation with MnO₂ of fluorine-containing arylhydroxylamines possessing the CH-fragment in an α-position.     

Fluorine-containing carbocations. IV. The use of salt solutions of stable polyfluorinated α,α-difluorobenzyl and α-fluorodiphenylmethyl cations in antimony pentafluoride in the synthesis of polyfluorinated benzoic acids,benzophenones and diphenyldifluoromethanes

Polyfluorinated benzoic acids have been prepared by the hydrolysis of solutions of salts of polyfluorinated α,α-difluorobenzyl cations in SbF₅. Polyfluorinated benzophenones and diphenyldifluoromethanes have been obtained both by hydrolysis and by pouring into HF solutions of the salts of polyfluorinated α-fluorodiphenylmethyl cations.     

1, 2-, 1, 3- and 1, 4-Cyclohexanedicarboxylates of Cd and Mn with chain and layered structures

A systematic study has been carried out on the three isomeric cyclohexanedicarboxylates (CHDCs) formed by cadmium and manganese with the three isomeric dicarboxylic acids, in the presence or absence of amines. The CHDCs have been prepared under hydrothermal conditions and their structures established by X-ray crystallography. We have been able to isolate two-dimensional layered structures of 1,2-, 1,3- and 1,4-cyclohexanedicarboxylates and chain structures of 1,3- and 1,4-cyclohexanedicarboxylates. The infinite metal-oxygen-metal linkages are observed only in the case of the 1,2-dicarboxylate. In all the three isomeric cyclohexanedicarboxylates, the e,e conformation is most favored, although the 1,4-CHDCs often contain rings in both the e,e and the a,e conformations.     

Structure-driven design and synthesis of chiral dioxocyclam derivatives

Based on an analysis of previously reported structures and a potential geometry fit with substrates, a new family of chiral dioxocyclam derivatives have been designed. The synthesis of those ligands was accomplished starting from l-proline and α-d-amino acids (converted to β-amino acids) with a key step of macrocyclization reaction of amino esters. All ligands were converted into neutral copper(II) complexes (amide groups underwent deprotonation of upon treatment of ligands with copper(II) acetate). The complexes exhibit the desired shape of their active surfaces, as proved by X-ray analysis.     

Facile synthesis of γ-, α-, and ε-lactams by cyclodehydration of ω-amino acids on alumina or silica gel

It has been found that γ-, α-, and ε-amino acids cyclodehydrate easily to their corresponding lactams by the action of alumina or silica gel in boiling toluene.