- Research on solubility and bio-solubility of amino acids ionic liquids
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Herein, the synthesis of L-(+)-α-(positive butyl)-leucine ethyl ester ionic liquids with anions based on bromide (Br?), terafluoroborate (BF4?) and hexafluorophosphate (PF6?) were presented. The structures and purities of these amino acids ionic liquids (AAILs) were characterized by 1H NMR and the determinations of water content. The interaction energies of AAILs-solvents/amino acids and dipole moment of AAILs were obtained through ab initio at MP2/6-311G?++(2d, p). The relationships between the solubility of AAILs and common solvents, molecular structure and the interaction energies of AAILs-solvents along with the influences of temperature and molecular structure on the bio-solubility of AAILs were discussed systematically. The results revealed that the solubility of the title AAILs increased firstly and then decreased with decreasing dielectric constant of solvent. With the dipole moment of AAILs and hydrogen bond interaction increasing, the solubility in polar solvents had an increasing trend. With the interaction energies of AAILs-solvents becoming bigger, AAILs can be easily dissolved in the solvents. The dissolution of amino acids in AAILs was largened with temperature increasing. Additional, the ease or difficulty of dissolution for amino acids in AAILs can be predicted by theoretical calculation. This prediction is consistent with the dissolution behavior of AAILs.
- Tian, Tian,Hu, Xiaoling,Guan, Ping,Ding, Xiaoqi
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- Stereoretentive N-Arylation of Amino Acid Esters with Cyclohexanones Utilizing a Continuous-Flow System
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The N-arylation of chiral amino acid esters with minimal racemization is a challenging transformation because of the sensitivity of the α-stereocenter. A versatile synthetic method was developed to prepare N-arylated amino acid esters using cyclohexanones as aryl sources under continuous-flow conditions. The designed flow system, which consists of a coil reactor and a packed-bed reactor containing a Pd(OH)2/C catalyst, efficiently afforded the desired N-arylated amino acids without significant racemization, accompanied by only small amounts of easily removable co-products (i. e., H2O and alkanes). The efficiency and robustness of this method allowed for the continuous synthesis of the desired product in very high yield and enantiopurity with high space-time yield (74.1 g L?1 h?1) and turnover frequency (5.9 h?1) for at least 3 days.
- Ichitsuka, Tomohiro,Komatsuzaki, Shingo,Masuda, Koichiro,Koumura, Nagatoshi,Sato, Kazuhiko,Kobayashi, Shū
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supporting information
p. 10844 - 10848
(2021/05/31)
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- Rh(iii)-Catalyzed diastereoselective transfer hydrogenation: An efficient entry to key intermediates of HIV protease inhibitors
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A highly efficient diastereoselective transfer hydrogenation of α-aminoalkyl α′-chloromethyl ketones catalyzed by a tethered rhodium complex was developed and successfully utilized in the synthesis of the key intermediates of HIV protease inhibitors. With the current Rh(iii) catalyst system, a series of chiral 3-amino-1-chloro-2-hydroxy-4-phenylbutanes were produced in excellent yields and diastereoselectivities (up to 99% yield, up to 99?:?1 dr). Both diastereomers of the desired products could be efficiently accessed by using the two enantiomers of the Rh(iii) catalyst.
- Chen, Gen-Qiang,Lang, Qi-Wei,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie,Wang, Fangyuan,Wu, Ting,Yin, Congcong,Zhang, Xumu,Zheng, Long-Sheng
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supporting information
p. 3119 - 3122
(2020/03/23)
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- Stereospecific Synthesis of 3,4-Dihydro-2 H-naphtho-1,4-oxazin-2-ones by Unification of Benzoxepine-4-carboxylates with Chiral Amino Acid Ethyl Esters
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A novel and efficient stereocontrolled method has been developed for the preparation of chiral 3,4-dihydro-2H-naphtho[1,2-b][1,4]oxazin-2-ones by the reaction of benzoxepine-4-carboxylates with chiral amino acid ethyl esters for the first time. The chiral 3,4-dihydro-2H-naphtho-1,4-oxazinones have been achieved in one step by the formation of C-N, C-C, and C-O bonds.
- Bhimapaka, China Raju,Kasagani, Veera Prasad,Kurma, Siva Hariprasad
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supporting information
p. 2976 - 2983
(2020/03/23)
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- Characterization and cytotoxicity evaluation of biocompatible amino acid esters used to convert salicylic acid into ionic liquids
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The technological utility of active pharmaceutical ingredients (APIs) is greatly enhanced when they are transformed into ionic liquids (ILs). API-ILs have better solubility, thermal stability, and the efficacy in topical delivery than solid or crystalline drugs. However, toxicological issue of API-ILs is the main challenge for their application in drug delivery. To address this issue, 11 amino acid esters (AAEs) were synthesized and investigated as biocompatible counter cations for the poorly water-soluble drug salicylic acid (Sal) to form Sal-ILs. The AAEs were characterized using 1H and 13C NMR, FTIR, elemental, and thermogravimetric analyses. The cytotoxicities of the AAE cations, Sal-ILs, and free Sal were investigated using mammalian cell lines (L929 and HeLa). The toxicities of the AAE cations greatly increased with inclusion of long alkyl chains, sulfur, and aromatic rings in the side groups of the cations. Ethyl esters of alanine, aspartic acid, and proline were selected as a low cytotoxic AAE. The cytotoxicities of the Sal-ILs drastically increased compared with the AAEs on incorporation of Sal into the cations, and were comparable to that of free Sal. Interestingly, the water miscibilities of the Sal-ILs were higher than that of free Sal, and the Sal-ILs were miscible with water at any ratio. A skin permeation study showed that the Sal-ILs penetrated through skin faster than the Sal sodium salt. These results suggest that AAEs could be used in biomedical applications to eliminate the use of traditional toxic solvents for transdermal delivery of poorly water-soluble drugs.
- Moshikur, Rahman Md.,Chowdhury, Md. Raihan,Wakabayashi, Rie,Tahara, Yoshiro,Moniruzzaman, Muhammad,Goto, Masahiro
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- The reactions of α-amino acids and α-amino acid esters with high valent transition metal halides: synthesis of coordination complexes, activation processes and stabilization of α-ammonium acylchloride cations
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Titanium tetrachloride smoothly reacted with a selection of α-amino acids (aaH) in CH2Cl2 affording yellow to orange solid coordination compounds, 1a-d, in 70-78% yields. The salts [NHEt3][TiCl4(aa)], 2a-b, were obtained from TiCl4/aaH/NEt3 (aa = l-phenylalanine, N,N-dimethylphenylalanine), in 60-65% yields. The complex , 3, was isolated from the reaction of l-proline with NbCl5/NHiPr2, performed in CH2Cl2 at room temperature. The X-ray structure of 3 features a bridging (E)-1,2-bis(3,4-dihydro-2H-pyrrol-5-yl)ethene-1,2-diolate ligand, resulting from the unprecedented C-C coupling between two proline units. Unusually stable α-ammonium acyl chlorides were prepared by the reactions of PCl5/MCln (MCln = NbCl5, WCl6) with l-proline, N,N-dimethylphenylalanine, sarcosine and l-methionine. MX5 (M = Nb, Ta; X = F, Cl) reacted with l-leucine methylester and l-proline ethylester to give ionic coordination compounds, [MX4L2][MX6] (M = Nb, L = Me2CHCH2CH(NH2)CO2Me, X = F, 9; Cl, 11a; M = Nb, X = Cl, , 11c; Ta, 11d), in moderate to good yields. [NbCl5(Me2CHCH2CHNH3CO2Me)][NbCl6], 12, was isolated as a co-product of the reaction of NbCl5 with l-leucine isopropylester, and crystallographically characterized. The reaction of NbCl5 with l-serine isopropylester afforded NbCl3(OCH2CHNHCO2iPr), 13, in 66% yield. The activation of the ester O-R bond was observed in the reactions of l-leucine methyl ester with NbF5 and l-proline ethyl ester with MBr5 (M = Nb, Ta), these reactions proceeding with the release of EtF and EtBr, respectively. All the metal products were characterized by analytical and spectroscopic methods, while DFT calculations were carried out in order to provide insight into the structural and mechanistic aspects.
- Biancalana, Lorenzo,Bortoluzzi, Marco,Ferretti, Eleonora,Hayatifar, Mohammad,Marchetti, Fabio,Pampaloni, Guido,Zacchini, Stefano
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p. 10158 - 10174
(2017/02/15)
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- Design and synthesis of a s-triazene based asymmetric organocatalyst and its application in enantioselective alkylation
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A very efficient chiral organocatalyst was prepared from the readily available cyanuric chloride. The asymmetric catalyst exhibited a highly enantioselective catalytic performance for the alkylation of a glycinate Schiff base, which provides a useful procedure for the enantioselective synthesis of structurally diverse natural and unnatural α-alkyl-α-amino acids.
- Mangawa, Shrawan K.,Singh, Ashawani K.,Awasthi, Satish K.
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p. 61144 - 61147
(2015/08/03)
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- Stereochemistry and conformation of skyllamycin, a non-ribosomally synthesized peptide from streptomyces sp. Acta 2897
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Skyllamycin is a non-ribosomally synthesized cyclic depsipeptide from Streptomyces sp. Acta 2897 that inhibits PDGF-signaling. The peptide scaffold contains an N-terminal cinnamoyl moiety, a β-methylation of aspartic acid, three β-hydroxylated amino acids and one rarely occurring α-hydroxy glycine. With the exception of α-hydroxy glycine, the stereochemistry of the amino acids was assigned by comparison to synthetic reference amino acids applying chiral GC-MS and Marfey-HPLC analysis. The stereochemistry of α-hydroxy glycine, which is unstable under basic and acidic conditions, was determined by conformational analysis, employing a combination of data from NOESY-NMR spectroscopy, simulated annealing and free MD simulations. The simulation procedures were applied for both R- and S-configured α-hydroxy glycine of the skyllamycin structure and compared to the NOESY data. Both methods, simulated annealing and free MD simulations independently support S-configured α-hydroxy glycine thus enabling the assignment of all stereocenters in the structure of skyllamycin and devising the role of two-component flavin dependent monooxygenase (Sky39) as S-selective.
- Schubert, Vivien,Di Meo, Florent,Saaidi, Pierre-Loic,Bartoschek, Stefan,Fiedler, Hans-Peter,Trouillas, Patrick,Suessmuth, Roderich D.
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p. 4948 - 4955
(2014/05/06)
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- Friedel-Crafts alkylation of natural amino acid-derived pyrroles with CF3-substituted cyclic imines
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Natural amino acid-derived ethyl 2-(1-pyrrolyl)alkanoates react with 2-trifluoromethyl-1-azacycloalkenes selectivity at the β-position of the pyrrole moiety to afford ethyl 2-[3-(1-trifluoromethyl-2-azacycloalkyl)pyrrol-1- yl]alkanoates.
- Shmatova, Olga I.,Shevchenko, Nikolay E.,Balenkova, Elizabeth S.,R?schenthaler, Gerd-Volker,Nenajdenko, Valentine G.
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- Synthesis and biological activity of mono- and diamides of 2,3-secotriterpene acids
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Amides of four types were synthesized derived from 2,3-seco-18αH- oleanane and 2,3-secolupane mono- and dicarboxylic acids. The spectrum of diamide derivatives was expanded with C3-C3′ and C28-C28′ biscondensed amides with two A-secotriterpene backbones obtained by the interaction of monocarboxylic A-seco acids with lysine. Among the synthesized monoand diamide derivatives, potential inhibitors of herpes simplex virus type 1 replication were found, namely, some compounds with an ethyl β-alaninate fragment (EC50 8.7 and 4.1 μM). The ethyl β-alaninate diamide was shown to combine antiherpetic and anti-HIV activity (EC50 5.1 μM). For the active compounds, the ratios of maximum tolerable concentrations to EC50 ranged from 9.7 to 40.8. The synthesized amides did not show any marked cytotoxic effects against human rabdomiosarcoma RD TE32, A549 lung carcinoma, and melanoma MS cell lines.
- Tolmacheva,Igosheva,Vikharev,Grishko,Savinova,Boreko,Eremin
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p. 186 - 193
(2013/08/23)
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- NMR determinations of the absolute configuration of α-chiral primary amines
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(Figure presented) We have established a methodology to determine the absolute configuration of α-chiral primary amines by derivatization to the corresponding imines with each enantiomer of 2′-methoxy-1,1′- binaphthalene-8-carbaldehyde (1). This methodology proceeds on the basis of modified Moshers method, and sufficiently large ΔδR S values can be obtained to elucidate the stereochemistry of the amines.
- Fukui, Hiroki,Fukushi, Yukiharu
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supporting information; experimental part
p. 2856 - 2859
(2010/08/22)
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- First and convergent synthesis of hybrid sulfonophosphinopeptides
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Figure Presented Hybrid sulfonophosphinopeptides were first and convergently synthesized in satisfactory to good yields via the Mannich-type reaction of N-protected 2-aminoalkanesulfonamides, aromatic aldehydes, and aryldichlorophosphines and subsequent aminolysis with amino esters.
- He, Fengdan,Meng, Fanhua,Song, Xiuqing,Hu, Wenxiang,Xu, Jiaxi
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supporting information; experimental part
p. 3922 - 3925
(2009/12/05)
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- Synthesis of diketopiperazines containing prolinyl unit - Cyclo(L-prolinyl-L-leucine), cyclo(L-prolinyl-L-isoleucine) and cyclo(L-tryptophyl-L-proline)
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Diketopiperazines cyclo(L-prolinyl-L-isoleucine) 4a, cyclo(L-prolinyl-L-leucine) 4b and cyclo(L-tryptophyl-L-proline) 6 were prepared from their respective suitably protected amino acid derivatives by standard peptide chemistry. Cyclo(L-(4-hydroxyprolinyl)-L-phenylalanine) 3, 4a and cyclo(L-prolinyl-L-tyrosine) 5 were tested for their antibacterial activity.
- Jhaumeer-Laulloo,Khodabocus,Jugoo,Jheengut,Sobha
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p. 765 - 768
(2007/10/03)
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- A mild and convenient procedure for the esterification of amino acids
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Chiral amino acids are esterified in high yield and purity at room temperature by stirring with amberlyst-15 in alcohols.
- Anand, Ramesh C.,Vimal
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p. 1963 - 1965
(2007/10/03)
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- Heterocyclic sulfonamide derivatives as antagonists of PAF and angiotensin II
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Compounds of formula (I), wherein: A represents: a) a --VR6 group wherein v is --C(=O), --C(=O)O--, --CH2 O--, --CH2 OC(=O)--, --C(=S)--, --CH2 OC(=O)NH--, --C(=S)O--, --CH2 S--, --C(=O)NHSO2 --, --SO2 NHC(=O)-- or --CH2 OSiPh2 --; b) a --CH2 NR9 R10 group or a --CONR9 R10 group wherein each of R9 and R10 is independently hydrogen, -alkyl-, -alkenyl-, -alkynyl, -cycloalkyl, -cycloalkenyl, pyridyl (any of which may optionally be substituted) or a group --D as defined above or R9 and R10 together with the nitrogen atom to which they are attached form a nitrogen-containing heterocyclic ring; c) a group Y where Y is a 5- or 6-membered optionally substituted heterocyclic ring containing one or more heteroatoms selected from nitrogen, oxygen and sulphur; or d) a group --CH2 Y or --C(=O)NHY; where Y is as defined above; B represents a 5- or 6-membered heterocyclic ring containing one or more nitrogen atoms in its ring, are antagonists of platelet activating factor (PAF) and/or antagonists of angiotensin II.
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- Amino acid derivatives as paf-receptor antagonists
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Compounds of general formula I: STR1 wherein W represents imidazo [4,5-c]pyridin-1-yl, imidazo [4,5-c]pyridin-3-yl and imidazo [4,5-c]pyridin-5-yl optionally substituted with one or more --C1 -C6 alkyl substituents; Z represents a) a divalent alkanediyl, alkenediyl or alkynediyl group; b) a --(CH2)q U(CH2)r -- group, optionally substituted, wherein q is an integer from 0-3, r is an integer from 0-3 and U is --O-- or --S--; Q represents a carbonyl, thiocarbonyl or sulphonyl group; B represents a) a --VR8 group wherein V is --C(=O)O-- or --CH2 O--; are antagonists of platelet activating factor (PAF).
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- Method for treating inflammation and compounds and compositions suitable for use therein
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The present invention relates to a method of treating an inflammatory condition, and to compounds and composition suitable for use in such a method, which compounds have the Formula: STR1 wherein: X is methylene, ethylene, ethyleneoxy, or oxygen; Q is STR2 where C' is a residue of a lipophilic amino acid, and Y is --CO2 H, --CH2 OH, --CONR1 R2, or --CO2 R1 where R1 and R2 hydrogen, alkyl, or aryl; R3 and R4 are, independently, hydrogen, alkyl or aryl; and A and B are, independently, hydrogen, fused phenyl, alkyl, aryl, alkaryl, aralkyl, alkoxy, alkoxyalkyl, halogen, or nitro; or pharmaceutically acceptable salts thereof.
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- Low molecular weight proteins as carriers for renal drug targeting. Preparation of drug-protein conjugates and drug-spacer derivatives and their catabolism in renal cortex homogenates and lysosomal lysates
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Low molecular weight proteins (LMWPs) are known to be reabsorbed and catabolized primarily by the proximal tubular cells of the kidneys. As such, LMWPs might serve as drug carriers that release drugs site-specifically in the kidney. We tested this concept in vitro by coupling different drugs to the LMWP lysozyme both directly (amide bond) and via different spacers: oligopeptides (amide bond), (poly-)α-hydroxy acids (ester bond), and a pH sensitive cis-aconityl spacer (amide bond). The capability of the kidney to release the parent drug from such drug-spacer derivatives and drug-LMWP conjugates by enzymatic or chemical hydrolysis of the bond was tested by incubation experiments in renal cortex homogenates and lysosomal lysates. Directly coupled conjugates of terminal carboxyl group containing drugs and lysozyme were catabolized to single amino acids, but did not result in release of the parent drug. The amide bond between the drug and the final amino acid (lysine) appeared to be stable in the incubation milieu. Different oligopeptide spacers coupled to the drugs showed similar results: the oligopeptide itself was cleaved but the amide bond between the drug and different single amino acids remained untouched. Only amide bonds of derivatives of carboxylic drugs with peptide structures themselves were cleaved. Some of the directly coupled conjugates of terminal amino drugs and oligopeptides showed clear release of the parent drug whereas others were stable. Terminal amino drugs were rapidly released from an acid-sensitive cis-aconityl spacer. Terminal carboxyl group containing drugs were enzymatically released from their glycolic and lactic ester spacers at different rates. These kinds of drugs were also released as parent drug from LMWP conjugates with ester spacers like L-lactic acid. Increasing spacer length by intercalating a tetra(L-lactic acid) molecule between the drug and the protein further increased the extent and rate of drug release, indicating increased accessability of the bond to the enzymes. Terminal amino group containing drugs were rapidly generated as parent drug from LMWP conjugates using an acid-sensitive spacer. In addition the conjugates were found to be adequately stable in plasma, considering their rapid clearance from the bloodstream. It is concluded that LMWPs may indeed be of use as carriers for specific renal delivery of drugs, since renal cortex homogenates and lysosomal lysates are able to catabolize the protein and generate the parent drug from drug-LMWP conjugates bearing suitable spacers. The option of enzymatic release is limited by the narrow specificity of the lysosomal enzymes. This has profound implications for the synthesis of suitable conjugates, since the nature of the drug itself, the type of bond and also spacer length largely determine whether release of the parent drug will occur. Tailor-made spacers containing the correct mode of attachment and the right spacer length are required for this option. Chemical hydrolysis using acid-sensitive linkers, is suggested as a viable alternative approach.
- Franssen,Koiter,Kuipers,Bruins,Moolenaar,De Zeeuw,Kruizinga,Kellogg,Meijer
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p. 1246 - 1259
(2007/10/02)
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- ENANTIOSELECTIVE SYNTHESES OF α-AMINO ACIDS FROM 10-SULFONAMIDO-ISOBORNYL ESTERS AND DI-t-BUTYL AZODICARBOXYLATE
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Successive treatment of chiral esters 7 with LDA/Me3SiCl and di-t-butyl azodicarboxylate/TiCl4 and Ti(OiPr)4 gave N,N-di-t-butoxycarbonylhydrazinoesters 11 which on deacylation, hydrogenolysis, transesterification and acidic hydrolysis furnished (2S)-α-amino acid hydrochlorides 13 in good overall yields, high enantiomeric purity and with efficient recovery of the alcohol auxiliary 4.Experimental evidence for the configuration and conformation of the intermediate O-silyl ketene acetals 1 is provided.
- Oppolzer, Wolfgang,Moretti, Robert
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p. 5541 - 5552
(2007/10/02)
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- Water soluble 3,5-diacetamido-2,4,6-triiodobenzoic acid derivatives
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The invention relates to novel water soluble 3,5-diacetamido-2,4,6-triiodobenzoic acid derivatives, the method for making the same and their use as X-ray contrast agents for vasography, urography, myelography, artrography, fistulography and salpingography.
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The Hofmann-Loeffler-Freytag reaction, carried out by irradiation in sulphuric acid of N-chloro-l-amino-acids 3a-d, gives δ-chlorinated compounds which can be cyclized to l-prolines 4a-e. This convenient synthesis does not affect the asymmetric centres of
- Titouani, S.Lafquih,Lavergne,Viallefont,Jacquier
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p. 2961 - 2965
(2007/10/02)
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