Some reactions of fluorosulfonyldifluoroacetic acid with N-heterocyclic compounds

Difluorocarbene generated from the decomposition of fluorosulfonyldifluoroacetic acid (2)reacted with various sodium salts of N-heterocyclic compounds(1) giving the corresponding difluoro-methylated products in acetonitrile at 10—40℃.Benzotriazole(1a),benzimidazole(1b) and imidazole(1c) were converted into 1-(difluoromethyl)benzotriazole(3a),1-(difluoromethyl)benzimidazole(3b) and1-(difluoromethyl)imidazole(3c)respectively.Indole(1d)reacted with 2 to give -(fluorosulfonyldifluoro-acetate)indole(2d) rather than the expected difluoromethylated derivatives.     

Stereoselective allylation reactions of acyclic and chiral α-amino-β-hydroxy aldehydes

Stereoselective allylation reactions of acyclic and chiral α-amino-β-hydroxy aldehydes affording chiral β-amino-α,γ-diols are described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The reactions of anti-α-NHCbz-β-OTBS substrates mediated by SnCl₄ afforded syn-selective products. The same reaction conditions also gave satisfactory results for the reactions of syn-α-NHCbz-β-OTBS substrates. The mechanism involves α-chelation between the amido group and aldehyde oxygen.     

Solution and fluorous phase synthesis of β,β-difluorinated 1-amino-1-cyclopentane carboxylic acid derivatives

An efficient protocol for the preparation of β,β-difluorinated 1-amino-1-cyclopentane carboxylic acid derivatives was developed. 2,2-Difluro-4-phenyl-3-butenoic acid 6 was used as substrate for the preparation of the starting vinyl difluoro imino esters 8. The key steps of this methodology rely on the chemo- and diastereoselective addition of allylzinc bromides over the iminic functionality of 8 and subsequent RCM reaction. This synthetic sequence was successfully applied to fluorous synthesis.     

Stereoselective allylation reactions of acyclic and chiral α-amino-β-hydroxy aldehydes 3: Total synthesis of (+)-1-epi-castanospermine

Stereoselective allylation reactions of acyclic, chiral α-amino-β-hydroxy aldehydes containing four contiguous stereocenters were conducted. Allylation mediated by MgBr₂?OEt₂ afforded the anti-product. A plausible mechanism of the allylation reaction is also described. The resulting allylation product was used for the total synthesis of (+)-1-epi-castanospermine.     

Analytical techniques for the detection of α-amino-β-methylaminopropionic acid

The non-protein amino acid L-α-amino-β-methylaminopropionic acid (BMAA) has been linked to several neurodegenerative diseases. Its presence in trace amounts in complex sample such as bacterial, plant and mammalian tissue extracts and hydrolyzates makes analysis a complicated process requiring good analytical technique. There are conflicting reports in the literature regarding the presence or absence of BMAA in key samples, but the absence of standardized or validated methods makes comparison of the disparate findings difficult to compare. This critical review will summarize the historic and recent literature, and provide suggestions for improving the methods currently in practice.     

Stereo- and regioselective synthesis of β-amino-β-tetrazolylvinylphosphonates

Addition of 5-substituted tetrazoles to dimethyl [(N,N-diisopropylamino)ethynyl]phosphonate proceeds regio- and stereoselectively to yield (Z)-[2-diisopropylamino-2-(tetrazolyl)vinyl]phosphonic acid dimethyl esters. The Z-configuration of the products was confirmed by ¹Н NMR spectroscopy and single-crystal X-ray diffraction. The reactions occur via nucleophilic attack of tetrazole involving predominantly the N-1 atom of the tetrazole ring.     

Kinetic and mechanism of reactions of L-α-Glutamic acid and L-Glutamine with pyridoxal

The kinetics and mechanisms of condensation of pyridoxal with L-α-glutamic acid and L-glutamine were studied by UV spectroscopy and polarimetry. L-α-Glutamic acid reacts with pyridoxal to form a Schiff base whose subsequent hydrolysis gives rise to pyridoxamine and α-ketoglutaric acid. The reaction of Lglutamine with pyridoxal involves the Γ-NH₂ group and affords a Schiff base whose subsequent hydrolysis gives rise to pyridoxamine and L-α-glutamic acid.     

Microwave-assisted synthesis of 6-amino-β-cyclodextrins

A general microwave-assisted procedure for the synthesis of 6-amino-β-cyclodextrins is reported. Mono-tosyl-β-cyclodextrin was used as the starting material in a one-pot route employing a solvent-free microwave-assisted reaction with a liquid amine. Shorter reaction times were observed for the formation of 6-amino-β-cyclodextrins using this novel microwave approach compared to the thermal procedure.     

Proton transfer reactions and dynamics of sulfonic acid group in Nafion®

Proton transfer reactions and dynamics of the hydrophilic group (-SO(3)H) in Nafion? were studied at low hydration levels using the complexes formed from CF(3)SO(3)H, H(3)O(+) and nH(2)O, 1 ≤n≤ 3, as model systems. The equilibrium structures obtained from DFT calculations suggested at least two structural diffusion pathways at the -SO(3)H group namely, the "pass-through" and "pass-by" mechanisms. The former involves the protonation and deprotonation at the -SO(3)H group, whereas the latter the proton transfer in the adjacent Zundel complex. Analyses of the asymmetric O-H stretching frequencies (ν(OH)) of the hydrogen bond (H-bond) protons showed the threshold frequencies (ν(OH*)) of proton transfer in the range of 1700 to 2200 cm(-1). Born-Oppenheimer Molecular Dynamics (BOMD) simulations at 350 K anticipated slightly lower threshold frequencies (ν(A)(OH*,MD)), with two characteristic asymmetric O-H stretching frequencies being the spectral signatures of proton transfer in the H-bond complexes. The lower frequency (ν(A)(OH,MD))) is associated with the oscillatory shuttling motion and the higher frequency (ν(B)(OH,MD))) the structural diffusion motion. Comparison of the present results with BOMD simulations on protonated water clusters indicated that the -SO(3)H group facilitates proton transfer by reducing the vibrational energy for the interconversion between the two dynamic states (Δν), resulting in a higher population of the H-bonds with the structural diffusion motion. One could therefore conclude that the -SO(3)H groups in Nafion? act as active binding sites which provide appropriate structural, energetic and dynamic conditions for effective structural diffusion processes in a proton exchange membrane fuel cell (PEMFC). The present results suggested for the first time a possibility to discuss the tendency of proton transfer in H-bond using Δν(BA)(OH,MD)) and provided theoretical bases and guidelines for the investigations of proton transfer reactions in theory and experiment.     

Synthesis of both enantiomers of methylenolactocin,nephrosterinic acid and protolichesterinic acid via tandem aldol–lactonization reactions

Both forms of the enantiomerically pure methylenolactocin, nephrosterinic and protolichesterinic acid have been synthesized via tandem aldol–lactonization reactions from corresponding optically active itaconate–anthracene adducts.     

β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine

A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α-difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α-oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro-β-phenylalanine derivatives (4). Enantiomerically pure β,β-difluorophenylalanine (l-4a) was obtained when α,α-difluoro-α-phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pK_a values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (K_i 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.     

Synthesis of α-amino-β-keto-esters (β-oxodipeptides)

The synthesis of α-amino-β-keto-esters (β-oxo dipeptides) was studied. Corresponding α-amino-β-ketoesters were prepared from BOC-(L)-Valine and BOC-(L)-isoleucine by coupling with (D,L)-threonine hydrochloride and oxidation with Dess-Martin periodinane (DMP) with a total yield of 48% and 38%, respectively. __________ Translated from Chemistry Online, 2007, 70(10): 793–796 [译自: 化学通报]     

Synthesis and reactions of 4-amino-3-carbethoxy-1,2-dihydrospiro(naphthalene-2,1′-cyclopentane)

Addition of benzylmagnesium chloride to cyclopentylidenecyanoacetic ester gives 1-benzyl-1-(cyanocarbethoxymethyl)cyclopentane and this can be cyclized to 4-amino-3-carbethoxy-1,2-dihydrospiro-(naphthalene-2,1-cyclopentane). Acylation of the obtained aminoester with carboxylic acid chlorides produces the corresponding amides (which can react with an excess of benzoyl chloride). It can also react with orthoformic ester. In both cases the product can then react with hydrazine hydrate. Treatment of the same aminoester with caprolactam gives a tetrahydrospiro(benzo[h]quinazoline-5,1-cyclopentane) derivative.A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, Yerevan 375014. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 820–823, June, 1998.     

Iodolactonization of 3-amino-4-pentenoic acid: a stereoselective synthesis of syn-γ-hydroxy-β-amino acids

The reaction of (S)-3-N-Cbz-4-pentenoic acid with iodine in acetonitrile in the presence of AgOTf gave the cis-iodo-lactone 6 in excellent yield and in a highly diastereoselective manner. The substitutions of the iodine in 6 by different Grignard reagents in the presence of CuI and the subsequent conversions into the functionalized syn-γ-hydroxy-β-amino acids have been investigated. By the above reaction sequence, (3S,4S)-3-amino-4-hydroxy-5-cyclohexyl pentanoic acid was synthesized with high enantioselectivity.     

Complex containing a Lewis acid and Brønsted acid for the catalytic reactions of aza-Michael addition

The novel efficient complex catalyst containing a Lewis acid and a Brønsted acid have been prepared by the reaction of proline ion liquid and cuprous iodide. The catalyst was characterized by FT-IR techniques using pyridine as probe molecule. A fast, mild, and quantitative procedure for aza-Michael addition reactions between various amines and α,β-unsaturated carbonyl compounds and nitriles has been developed using the novel complex catalyst. The results showed that the novel catalyst owned high activities for the reactions with excellent yields within 1 min.     

c-4-Amino-t-3-hydroxy-r-1-cyclohexanecarboxylic acid and cis-4-amino-3-oxo-1-cyclohexanecarboxylic acid—mimetics of dipeptides with a twisted cis-amide bond

The stereoselective synthesis of the title compounds has been performed. The relative configuration of methyl c-4-(tert-butoxycarbonylamino)-t-3-hydroxy-r-1-cyclohexanecarboxylate was confirmed by X-ray diffraction methods and its conformation in solution analyzed by NMR. The peptides containing this compound were synthesized and resolved into pure diastereoisomeric forms. Their absolute configuration was determined by independent stereospecific synthesis.     

Regio- and π-facial selective Lewis acid interceded Diels-Alder reactions of α-dienyl-β-lactams: an indepth analysis

The regio-, diastereo-, and π-facial selective Lewis acid mediated Diels-Alder reactions of cis/trans-3-butadienyl-2-azetidinones with unsymmetrical dienophiles viz. methyl acrylate, dimethyl fumarate, and acrolein leading to the synthesis of diastereomerically pure and biologically potent 1,3,4-trisubstituted-2-azetidinones are reported. Theoretical calculations at HF/6-31G^∗∗ and 6-31G^∗∗/DFT levels have been performed to support the observed π-facial selectivity. The formation of diastereomerically pure ‘endo’ adducts is supported by the X-ray diffraction studies.