Marfey’s reagent for chiral amino acid analysis: A review

Summary. The present paper describes characteristics and application of Marfeys reagent (MR) including general protocols for synthesis of the reagent and diastereomers along with advantages, disadvantages and the required precautions. Applications, and comparison with other derivatizing agents, for the resolution of complex mixtures of DL-amino acids, amines and non-proteinogenic amino acids, peptides/amino acids from microorganisms, cysteine residues in peptides, and evaluation of racemizing characteristics have been discussed. Separation mechanisms of resolution of amino acid diastereomers and replacement of Ala–NH₂ by suitable chiral moieties providing structural analogs and different chiral variants and their application as a derivatizing agent to examine the efficiency, and reactivity of the reagent have been focussed. Use of MR for preparing CSPs for direct enantiomeric resolution has also been included.On leave from Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India.     

Fluorescent-labeled single-strand ATP aptamer DNA: chemo- and enantio-selectivity in sensing adenosine

One of the intriguing applications of aptamers is sensing molecules. In principle, an aptamer can specifically recognize and bind to a unique ligand, leading to a structural change of an aptamer. By acquiring information for the structural change, the detection of the ligand can be achieved. To design and explore an aptamer molecule to detect adenosine, we have synthesized some ATP aptamer variants labeled with donor and acceptor fluorophores. Although the fluorescent response of the aptamer variants was highly dependent on experimental temperature, we have found one of the variants showing suitable fluorescent response by titration with adenosine. The aptamer variant showed remarkable selectivity for adenosine over the other ribonucleosides. On the other hand, the enantio-specificity of the aptamer variant in the ligand recognition was not enough to selectively detect d-adenosine over l-adenosine.     

Asymmetric bioreduction of racemic 5,6,7,8-tetrahydro-8-methyl-1,3-dimethoxynaphthalen-6-one to the corresponding chiral β-tetralols

The synthesis of racemic 5,6,7,8-tetrahydro-8-methyl-1,3-dimethoxynaphthalen-6-one 1 was performed and the bioreduction to the corresponding β-tetralols was studied with respect to the stereochemical course and optical purity of the products; in particular the 6S,8S enantiomer corresponding to the dimethyl derivative of the natural compound feroxidin was isolated. The biomass of: Aspergillus niger, Cladosporium cladosporioides, Candida lypolitica, Bacillus megatherium, Rhodotorula minuta, R. flava, R. rubra, Beauveria bassiana and Baker's yeast were used as biocatalysts. Relative and absolute configurations of the obtained β-tetralols were established by comparison with those of the natural feroxidin.     

Chimeric analogs of human β-defensin 1 and θ-defensin disrupt pre-established bacterial biofilms

Antibiofilm activity of several human defensin analogs that have the ability to kill planktonic bacteria, against pre-established biofilms of Escherichia coli MG1655 and Staphylococcus aureus NCTC 8530 were examined. Linear and linear fatty acylated analogs did not show any activity while disulfide constrained analogs disrupted pre-established S. aureus biofilms. Chimeric analogs of human β-defensin 1 and θ-defensin, hBTD-1 and [d]hBTD-1 were highly active against S. aureus biofilms. Among the analogs tested, only the d-enantiomer [d]hBTD-1 showed activity against E. coli biofilm. Our study provides insights into the structural requirements for the eradication of pre-established biofilms in defensin analogs.     

Cyclomaltooligosaccharide-assisted spectroscopic discrimination of phthalimido-derived amino acids through the formation of molecular aggregates

Spectroscopic evidence was used to demonstrate the formation of molecular associates in an aqueous solution of phthalimido tryptophan. These molecular associates are loosely formed through pi-pi aromatic stacking, properties that are not sufficient to cause NMR spectroscopic enantiomeric discrimination. A cyclomaltooligosaccharide with a larger cavity, such as cyclomaltooctaose (gamma-cyclodextrin), is capable of forming a ternary complex with these molecular associates and enhances pi-pi aromatic stacking interactions, resulting in NMR enantiomeric discrimination. Electrospray-ionization mass spectroscopy (ESIMS) and NOESY two-dimensional NMR spectroscopic methods were used to study these complexes. Association constants and thermodynamic data for these cyclomaltooligosaccharide complexes were also estimated.     

Enantiomeric composition analysis of pranoprofen in equine plasma and urine by chiral liquid chromatography-tandem mass spectrometry in selected reaction monitoring mode

The enantioseparation of pranoprofen after its addition in racemic form into equine plasma and urine was conducted by chiral liquid chromatography-tandem mass spectrometry in selected reaction monitoring mode. The methods for the assay of both enantiomers were linear (r≥0.9943) in the low range from 0.001 to 0.1μg/mL and high range from 0.01 to 1.0μg/mL with good precision (% RSD≤5.6) and accuracy (% RE=-5.3 to 1.9). When racemic pranoprofen was orally administered to four horses at a single dose of 3.1mg/kg, the median plasma concentrations of (R)-pranoprofen were lower than the levels of (S)-pranoprofen from start to finish. In contrast, the urinary level of (R)-pranoprofen was 2.5 fold higher than (S)-pranoprofen level for the first 6h, followed by its rapid decrease down below (S)-pranoprofen concentration. Monitoring of the R/S ratios in equine urine may be useful for the prevention of false positive in horse doping test.     

Sustainable synthesis and applications of polyhydroxyalkanoates (PHAs) from biomass

Polyhydroxyalkanoates (PHAs) belong to group of biopolymers that have in recent times received growing research interest as a result of being eco-friendly and close characteristics with petrochemical based plastics. Alternatives to utilization of synthetic plastics are being explored since synthetic plastics are non-recyclable and non-biodegradable in nature. One of the innovations of Green Chemistry is utilization of renewable feedstocks such as biomass to achieve sustainable development with future circular economy. Bio-based products are of great interest to sustainable development as a result of diminishing fossil fuel reserves and rising environmental concerns. This review summarizes the productions of PHAs from renewable feedstocks such as lignocellulose, crude glycerol, levulinic acid (LA), palm-oil mill effluents (POME) and waste oils. The production of bio-based polymers has become much more professional and differentiated in recent years. Presently, there are bio-based alternatives for practically every application, therefore, this review presents applications of PHA in bio-refinery, medical sectors, agriculture sector, construction industry, and in packaging industry. The cost analysis of PHA from renewable sources with commercially available ones and potential to attain circular economy were also stressed. The reasons for this shift are connected to the non-renewability of fossil-based resources, the deteriorating environmental impacts, and the lack of biodegradability of the petroleum-produced materials.     

Pinus halepensis,Pinus pinaster,Pinus pinea and Pinus sylvestris Essential Oils Chemotypes and Monoterpene Hydrocarbon Enantiomers,before and after Inoculation with the Pinewood Nematode Bursaphelenchus xylophilus

Pinewood nematode (PWN), Bursaphelenchus xylophilus, is the causal agent of pine wilt disease, a serious threat to global forest populations of conifers, especially Pinus spp. A time‐course study of the essential oils (EOs) of 2‐year‐old Pinus halepensis, Pinus pinaster, Pinus pinea and Pinus sylvestris following inoculation with the PWN was performed. The constitutive and nematode inoculation induced EOs components were analyzed at both the wounding or inoculation areas and at the whole plant level. The enantiomeric ratio of optically active main EOs components was also evaluated. External symptoms of infection were observed only in P. pinaster and P. sylvestris 21 and 15 days after inoculation, respectively. The EO composition analysis of uninoculated and unwounded plants revealed the occurrence of chemotypes for P. pinaster, P. halepensis and P. sylvestris, whereas P. pinea showed a homogenous EO composition. When whole plants were evaluated for EO and monoterpene hydrocarbon enantiomeric chemical composition, no relevant qualitative and quantitative differences were found. Instead, EO analysis of inoculated and uninoculated wounded areas revealed an increase of sesquiterpenes and diterpenic compounds, especially in P. pinea and P. halepensis, comparatively to healthy whole plants EOs.     

Synthesis of optically active lipidicα-amino acids and lipidic 2-amino alcohols

Summary Lipidic-amino acids (LAAs) are a class of compounds combining structural features of amino acids with those of fatty acids. They are non-natural-amino acids with saturated or unsaturated long aliphatic side chains. Synthetic approaches to optically active LAAs and lipidic 2-amino alcohols (LAALs) are summarized in this review. A general approach to enantioselective synthesis of saturated LAAs is based on the oxidative cleavage of 3-amino -1,2-diols obtained by the regioselective opening of enantiomerically enriched long chain 2,3-epoxy alcohols. Unsaturated LAAs are prepared in their enantiomeric forms by Wittig reactionvia methyl (S)-2di-tert-butoxycarbonylamino-5-oxo-pentanoate. This key intermediate aldehyde is obtained by selective reduction of dimethyl N,N-di-Boc glutamate with DIBAL. (R) or (S) LAALs may be prepared starting from D-mannitol or L-serine. LAAs are converted into LAALs by chemoselective reduction of their fluorides using sodium borohydride with retention of optical purity. Replacement of the hydroxyl group of LAALs by the azido group, followed by selective reduction leads to unsaturated optically active lipidic 1,2-diamines.Abbreviations Bn benzyl - Boc tert-butoxycarbonyl - DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone - DET diethyl tartrate - DIBAL diisobutyl aluminum hydride - DMAP 4-dimethylaminopyridine - DMF N,N-dimethylformamide - DMSO dimethyl sulfoxide - EDC N-ethyl-N-(3-dimethylaminopropyl)carbodiimide - Et₃N triethylamine - HMPA hexamethylphosphoramide - HOBt 1-hydroxybenzotriazole - KN(TMS)₂ potassium bis(trimethylsilyl)-amide - LAA lipidic-amino acid - LAAAl lipidic 2-amino alcohol - LDA lipidic 1,2-diamine - LP lipidic peptide - MPM-Cl p-methoxybenzyl chloride - MsCl methanesulphonyl chloride - MTPA -methoxy--(trifluoromethyl)phenylaccitc - PLA₂ phospholipase A₂ - TBIIP tert-butyl hydroperoxide - THF tetrahydrofuran - TMSCl trimethylsilyl chloride - Tr trityl - Z benzyloxycarbonyl     

QSAR study of the enantiomeric excess in asymmetric catalytic reactions with topological indices and an artificial neural network

The relationships between the enantiomer excess of product in catalytic asymmetric reactions and the structures of the catalysts or reagents in several asymmetric reactions were studied using a backpropagation (BP) neural network with topological indices and their chiral expansions. The trained network can be used to screen new asymmetric catalysts, estimate catalytic effects, design reaction environments, and prove or improve the proposed reaction mechanism.