- Synthesis of two biofriendly anionic surfactants (N-n-decanoyl-L-valine and N-n-decanoyl-L-leucine) and their mixed micellization with nonionic surfactant Mega-10 in Tris-buffer medium at pH 9
-
Two biofriendly anionic amino acid surfactants (AAS), N-n-decanoyl-l-valine (C10-val) and N-n-decanoyl-l-leucine (C10-leu) were synthesized and mixed micellization of them with nonionic surfactant N-decanoyl-N-methyl-glucamine (Mega-10) was investigated by tensiometry and fluorimetry in 50 mM Tris-buffer (pH = 9) medium at 298 K. The critical micelle concentration (cmc), surface properties, e.g., Gibbs surface excess (Γmax), area of exclusion per surfactant monomer (A min) and surface pressure at cmc (Πcmc) were determined. Gibbs free energy of micellization (ΔG0m) and Gibbs free energy of adsorption (ΔG0ads) were also determined. Both the free energy values are negative indicating the spontaneity and stability of the mixed micelles. The size of the micelles was determined by dynamic light scattering (DLS) measurements. The deviation of mixed micelles from the ideal behavior was discussed on the basis of Clint, Motomura, Rubingh (regular solution theory), Rosen and Maeda's theory. Rubingh-Holland theory was applied on the ternary systems made by these three surfactants. The compositions of mixed micelle, the activity coefficients and the corresponding interaction parameters were evaluated from these theories. The interaction parameters (β) are negative, indicating attractive interaction between the ionic and nonionic surfactants. The micellar aggregation number (Nagg) and micropolarity were evaluated using steady state fluorescence measurements and the packing parameter (P) was determined on the basis of Israelachvili's theory. The standard free energy changes associated with the transfer of surfactant tail due to micellization of pure, binary and ternary combinations of surfactants were determined from Nagarajan's model. We report for the first time in detail the binary and ternary combinations using amino acid based surfactants.
- Das, Sibani,Maiti, Susmita,Ghosh, Soumen
-
-
Read Online
- GENERAL APPROACH TO THE QUANTITATION OF SYNTHETIC EFFICIENCY IN SOLID-PHASE PEPTIDE SYNTHESIS AS A FUNCTION OF CHAIN LENGTH.
-
A model peptide, Leu-Ala-Gly-Val, was synthesized by solid-phase methods at increasing distnces from a 1% cross-linked polystyrene resin support. The efficiency of the synthesis was evaluated by quantitatively measuring the amounts of the deletion peptides Leu-Ala-Val and Leu-Gly-Val that were produced during the synthesis of the tetrapeptide. By inserting an oxymethylphenylacetyl group between this test peptide and the peptide chains used to provide spacers from the support, it was possible to selectively evaluate the quality of the tetrapeptide without interference by the spacer. Low and constant levels of deletion peptides were found. No significant effect of distance from the support or of peptide loading on the synthetic efficiency could be detected up to a chain length of 60 residues and a peptide-to-resin weight ratio of 4:1.
- Sarin,Kent,Mitchell,Merrifield
-
-
Read Online
- C2 symmetric copper (II) complexes of L-valine and L-phenyl alanine based chiral diimines for catalytic asymmetric Henry reaction
-
New C2 symmetric chiral diimines were synthesized from the amino acids L-valine and L-phenyl alanine. In situ copper (II) complexes of the chiral diimine ligands were found to catalyze asymmetric Henry reaction. The chiral nitro aldols were formed in excellent yield (99%) and ee (99%). The synthetic utility of the chiral catalysts were screened with various substituted prochiral aromatic and heteroaromatic aldehydes. Possible catalytic cycle for the chiral diimine copper complex catalyzed asymmetric Henry reaction has been proposed. The stereoselectivity of the asymmetric Henry reaction was discussed based on the transition state in the catalytic cycle.
- Ananthi, Nallamuthu,Johnson, S. Jesu,Kumar, K. Vinoth,Nixon, Peter Daniel
-
supporting information
(2021/05/19)
-
- Microwave-Assisted Ruthenium- and Rhodium-Catalyzed Couplings of α-Amino Acid Ester-Derived Phosphinamides with Alkynes
-
Two different types of new phosphinamide α-amino ester derivatives have been prepared in moderate to high yields via ruthenium(II) and rhodium(III)-catalyzed ortho-C?H functionalization under microwave irradiation. Specifically, the ortho-alkenylated phosphinamides were produced through coupling of phosphinamides containing an α-substituted or α,α-disubstituted α-amino ester with internal alkynes under ruthenium catalysis. In contrast, Ru and the more effective Rh-catalyzed coupling of the α-unsubstituted glycine ester phosphinamide with alkynes resulted in formation of oxidative annulation products, phosphaisoquinolin-1-ones. The developed methods feature the use of easily accessible starting materials, short reaction time, exclusive E-stereoselectivity (for ortho-alkenylation) and good functional group tolerance. The alkenylation reaction was readily scaled up to gram scale. Furthermore, the obtained alkenylated phosphinamide could be transformed into P-containing dipeptides through hydrolysis of the ester group in the catalysis product and subsequent condensation with an α-amino ester.
- Gong, Jun-Fang,Li, Xue-Hong,Song, Mao-Ping
-
supporting information
(2021/12/23)
-
- Post-synthetic functionalization of tryptophan protected peptide sequences through indole (C-2) photocatalytic alkylation
-
We report a selective, mild, and efficient C-H functionalization of tryptophan and tryptophan-containing peptides with activated α-bromo-carbonyl compounds under visible-light irradiation. The protocol efficiency is outlined by the wide substrate scope and excellent tolerance of sensitive functional groups present in the amino acid side chains. The method can be successfully extended to access pharmaco-peptide conjugate scaffolds.
- Ackermann, Lutz,Berlinck, Roberto G. S.,Bernardi, Darlon I.,Delgado, José A. C.,Kaplaneris, Nikolaos,Lima, Rafaely N.,Paix?o, Márcio W.
-
supporting information
p. 5758 - 5761
(2021/06/16)
-
- Eco-friendly synthesis of peptides using fmoc-amino acid chlorides as coupling agent under biphasic condition
-
Background: Agro-waste derived solvent media act as a greener process for the peptide bond formation using Nα-Fmoc-amino acid chloride and amino acid ester salt with in situ neutralization and coupling under biphasic condition. The Fmoc-amino acid chlorides are prepared by the reported procedure of freshly distilled SOCl2 with dry CH2Cl2. The protocol found many added ad-vantages such as neutralization of amino acid ester salt and not required additional base for the neu-tralization, and directly coupling take place with Fmoc-amino acid chloride gave final product dipeptide ester in good to excellent yields. The protocol occurs with complete stereo chemical integrity of the configuration of substrates. Here, we revisited Schotten-Baumann condition, instead of using inorganic base. Objective: To develop green protocol for the synthesis of peptide bond using Fmoc-amino acid chloride with amino acid esters salt. Methods: The final product isolated is analyzed in several spectroscopic and analytical techniques such as FT-IR,1H-,13C-NMR, Mass spectrometry and RP-HPLC to check stereo integrity and puri-ty of the product. Conclusion: The present method developed greener using natural agro-waste (lemon fruit shell ash) derived solvent medium for the reaction and not required chemical entity.
- Kantharaju, Kamanna,Khatavi, Santosh Y.
-
p. 699 - 707
(2021/08/23)
-
- Ribose conversion with amino acids into pyrraline platform chemicals-expeditious synthesis of diverse pyrrole-fused alkaloid compounds
-
One-pot conversion of sustainable d-ribose with l-amino acid, methyl esters produced pyrrole-2-carbaldehydes 5 in reasonable yields (32-63%) under pressurized conditions of 2.5 atm at 80 °C. The value-added pyrraline compounds 5 as platform chemicals were utilized for quick installation of poly-heterocyclic cores for the development of pyrrole-motif natural and artificial therapeutic agents. A pyrrole-fused piperazin-2-one scaffold 6 was prepared by reductive amination of pyrralines 5 with benzylamine. While further cyclization of pyrralines 5 with ethane-1,2-diamine produced pyrrolo-piperazin-2-ones 7 with an extra imidazolidine ring, the reaction with 2-amino alcohols derived from natural l-amino acids, alanine, valine, and phenylalanine, respectively provided pyrrolo-piperazin-2-ones 8, 9, and 10 with oxazolidine as the third structural core. Cell viability and an anti-inflammatory effect of the synthesized compounds were briefly tested by the MTT method and the Griess assay, among which 8h and 10g exhibited significant anti-inflammatory effects with negligible cell toxicity.
- Cho, Soohyeon,Gu, Lina,In, Ik Joon,Kim, Hakwon,Koo, Sangho,Lee, Taehoon,Wu, Bo
-
p. 31511 - 31525
(2021/11/30)
-
- Synthesis and antimalarial activity of (S)-methyl-(7-chloroquinolin-4-ylthio)acetamidoalquilate derivatives
-
The synthesis of five new (S)-methyl-(7-chloroquinolin-4-ylthio)acetamidoalquilate derivatives is carried out under a modified version of the Steglich esterification reaction between different l-amino acid methyl esters and 2-(7-chloroquinolin-4-ylthio)acetic acid. Two of the compounds showed significant inhibition (>50%) of β-hematin formation. The two active structures were tested in vivo as potential antimalarials in mice infected with Plasmodium berghei ANKA, a chloroquine susceptible strain. Compounds 6b and 6e exhibited antimalarial activity comparable to that of chloroquine.
- Colmenarez, Custodiana,Acosta, María,Rodríguez, Miguel,Charris, Jaime
-
p. 161 - 166
(2020/01/09)
-
- A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor γbinding Properties and Biological Activities
-
A proprietary library of novel N-Aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound 3a that possesses weak proadipogenic and peroxisome proliferator-Activated receptor γ(PPARI) activating properties. The systematic optimization of 3a, in order to improve its PPARγagonist activity, led to the synthesis of compound 7j (N-Aryl-substituted valine derivative) that possesses dual PPARI/PPARα agonistic activity. Structural and kinetic analyses reveal that 7j occupies the typical ligand binding domain of the PPARγagonists with, however, a unique high-Affinity binding mode. Furthermore, 7j is highly effective in preventing cyclin-dependent kinase 5-mediated phosphorylation of PPARγserine 273. Although less proadipogenic than rosiglitazone, 7j significantly increases adipocyte insulin-stimulated glucose uptake and efficiently promotes white-To-brown adipocyte conversion. In addition, 7j prevents oleic acid-induced lipid accumulation in hepatoma cells. The unique biochemical properties and biological activities of compound 7j suggest that it would be a promising candidate for the development of compounds to reduce insulin resistance, obesity, and nonalcoholic fatty liver disease.
- Peiretti, Franck,Montanari, Roberta,Capelli, Davide,Bonardo, Bernadette,Colson, Cécilia,Amri, Ez-Zoubir,Grimaldi, Marina,Balaguer, Patrick,Ito, Keiichi,Roeder, Robert G.,Pochetti, Giorgio,Brunel, Jean Michel
-
p. 13124 - 13139
(2020/12/02)
-
- Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile
-
Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a–4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1H NMR and 13C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+/K+-ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.
- Khan, Muhammad T.,Nadeem, Humaira,Khan, Arif-ullah,Abbas, Muzaffar,Arif, Muazzam,Malik, Nadia Shamshad,Malik, Zulkifal,Javed, Ibrahim
-
p. 1057 - 1072
(2020/08/13)
-
- The Asymmetric Aza-silyl-Prins Reaction: Synthesis of Enantiopure Piperidines
-
The design and development of the first asymmetric aza-silyl-Prins reaction is reported, giving rise to valuable and diverse piperidines and pipecolic acid derivatives in both high yields and as single enantiomers. The creation of a novel chiral auxiliary-homoallylic amine for the aza-silyl-Prins reaction is essential to its success.
- Mittapalli, Ramana R.,Guesné, Sebastien J. J.,Parker, Robert J.,Klooster, Wim T.,Coles, Simon J.,Skidmore, John,Dobbs, Adrian P.
-
supporting information
p. 350 - 355
(2019/01/11)
-
- Synthesis, Characterization, and Reactivity of an Ethynyl Benziodoxolone (EBX)-Acetonitrile Complex
-
The synthesis of a crystalline ethynyl-1,2-benziodoxol-3(1H)-one (EBX)-acetonitrile complex is described. EBX has been widely used as an active species for a variety of reactions; however, its high instability has so far prevented its isolation. The EBX-acetonitrile is self-assembled into a double-layered honeycomb structure through weak hypervalent iodine secondary interactions and hydrogen bonding. The N-ethynylation of a variety of sulfonamides using the EBX-acetonitrile complex as a substrate under mild conditions is also described.
- Yudasaka, Masaharu,Shimbo, Daisuke,Maruyama, Toshifumi,Tada, Norihiro,Itoh, Akichika
-
supporting information
p. 1098 - 1102
(2019/05/16)
-
- Benzoazepine-Fused Isoindolines via Intramolecular (3 + 2)-Cycloadditions of Azomethine Ylides with Dinitroarenes
-
Aminobenzaldehydes bearing a pendant 3,5-dinitrophenyl group react thermally with N-substituted α-amino acids to form unprecedented benzoazepine-fused isoindolines. The reaction proceeds via a dearomatization/rearomatization sequence involving an intramolecular (3 + 2)-cycloaddition between the in situ formed azomethine ylide and the dinitroarene. Various glycine derivatives are tolerated as well as branched substrates based on cyclic, α-mono-, and α,α-disubstituted amino acids, giving single diastereomers in many cases. The method is scalable and gives products with a nitro group ready for further manipulation.
- Wales, Steven M.,Rivinoja, Daniel J.,Gardiner, Michael G.,Bird, Melissa J.,Meyer, Adam G.,Ryan, John H.,Hyland, Christopher J. T.
-
supporting information
p. 4703 - 4708
(2019/06/27)
-
- Hydroxyphosphinylacetic acid as a chiral auxiliary compound
-
The aim of the presented research was to check whether 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid is a versatile chiral phosphonic auxiliary (readily seen in 31P NMR). The preliminary studies indicate that this compound may be used as chiral derivatizing agents for amines and alcohols, since the separation of selected examples of diastereomeric alcohols and amines in 31P NMR spectra was found to be satisfactory. The preliminary research about using this compound as a CSA are also promising.
- Majewska, Paulina
-
p. 585 - 590
(2019/01/04)
-
- Cocrystallization of Chiral N7,N16-bis (S-1-Phenylethyl)-1,4,10,13-Tetraoxo-7,16-Diazacyclooctadecane-7,16-Dicarboxamide with Hydrochlorides of Methyl Ethers of Leucine and Valine Enantiomers
-
An attempt to co-crystallize N7,N16-bis(S-1-phenylethyl)-1,4,10,13-tetraoxo-7,16-diazacyclooctadecane-7,16-dicarboxamide (1) with hydrochlorides of methyl ethers (HCMEs) of L- and D-valine and also L- and D-leucine results in separate crystallization of diazacrown-ether 1 (or its monohydrate 1·H2O) and HCMEs of respective α-amino acids. Crystal structures of D-leucine 1·H2O (1) and HCME (2) compounds, which were not described previously, are solved by single crystal X-ray diffraction.
- Fonari,Pluzhnik-Gladyr,Kamalov,Kravtsov, V. Kh.
-
p. 143 - 150
(2019/04/30)
-
- Rhodium-Catalyzed Enantioselective Synthesis of Oxazinones via an Asymmetric Ring Opening-Lactonization Cascade of Oxabicyclic Alkenes
-
The rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes is shown to be an efficient method for synthesizing chiral heterocycles. We demonstrate that the pairwise combination of chiral catalyst with chiral amino-acid-derived pronucleophiles results in a stereodivergent synthesis of diastereomeric hydroxyesters. A favorable conformational preference induces the subsequent lactonization of one diastereomer leading to the highly enantioselective synthesis of oxazinones.
- Yen, Andy,Pham, Anh Hoang,Larin, Egor M.,Lautens, Mark
-
supporting information
p. 7549 - 7553
(2019/10/02)
-
- Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain
-
The synthesis of celastrol analogues containing amino acid ester at the C(29) position and their evaluation for cytotoxic activities in?vitro were reported. The MTT test showed that a set of derivatives with lower IC50 values than that of the positive control group cisplatin and the parent compound celastrol, which exhibited greater antiproliferative activities. The most potent title compounds 2a and 2e exhibited cytotoxic activities in?vitro against HeLa and A549 cell lines with IC50 values of 0.371 and 0.237?μm, 0.235 and 0.109?μm, respectively. The apoptosis assay demonstrated that 2a and 2e can induces of A549 cell apoptosis in low concentrations. These results showed that 2a and 2e may be promising for further research as antitumor agents.
- Pang, Chaohai,Luo, Jinhui,Liu, Chunhua,Wu, Xuejin,Wang, Dingyong
-
-
- Identification of a 4-fluorobenzyl L-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT)
-
Novel L-valinate amide benzoxaboroles and analogues were designed and synthesized for a structure-activity-relationship (SAR) investigation to optimize the growth inhibitory activity against Trypanosoma congolense (T. congolense) and Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-L-valinate (5, AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg against both T. congolense and T. vivax in mouse models of infection (IP dosing) and in the target animal, cattle, dosed intramuscularly. AN11736 has been advanced to early development studies.
- Akama, Tsutomu,Zhang, Yong-Kang,Freund, Yvonne R.,Berry, Pamela,Lee, Joanne,Easom, Eric E.,Jacobs, Robert T.,Plattner, Jacob J.,Witty, Michael J.,Peter, Rosemary,Rowan, Tim G.,Gillingwater, Kirsten,Brun, Reto,Nare, Bakela,Mercer, Luke,Xu, Musheng,Wang, Jiangong,Liang, Hao
-
-
- Novel Fubinaca/Rimonabant hybrids as endocannabinoid system modulators
-
The discovery of novel modulators of the cannabinoid system is a current topic in medicinal chemistry. In this paper, we report nine novel carboxamides designed as hybrids of Fubinaca family compounds and Rimonabant. These hybrids were obtained by linking the 1-benzyl-2,5-dichloroindazole-3-carboxylic acid to different amino acids bearing a hydrophobic side chain and three different C-terminus. The new chemical entities were tested in vitro to evaluate their bioactivity by means of receptor binding assays and [35S]GTPγS stimulation assays to reveal their affinity and potency. We found that all compounds were able to bind to the cannabinoid receptors in the low nanomolar range with a marked selectivity towards the CB1 cannabinoid receptor. Some of them are full agonists, whereas the others act as partial agonists. These molecules could be potentially used as anti-obesity agents, antiemetic and analgesics.
- Stefanucci, Azzurra,Macedonio, Giorgia,Dvorácskó, Szabolcs,T?mb?ly, Csaba,Mollica, Adriano
-
p. 1595 - 1605
(2018/09/14)
-
- A valine ester hydrochloride synthetic method (by machine translation)
-
The invention relates to a valine ester hydrochloride synthetic method, at room temperature, anhydrous hydrogen chloride gas access is provided with the valine and alkyl alcohol of the reaction solvent in the reaction vessel to saturation, then stop ventilation, the system for heating to flow back to the completion of the reaction, the reaction process of tail gas in absorption, resulting absorption solution is used as the reaction solvent. The advantage of this invention is characterized in that: the invention will be valine and acidified alkyl alcohol reaction under normal temperature acyclic alkyl ester hydrochloride, the recycling of exhaust gas chlorination process, the process conditions are mild, the device does not have strict requirement, therefore, the process is simple, the operation is simple, high safety, low production cost, small influence on the environment. (by machine translation)
- -
-
Paragraph 0015; 0016
(2019/01/06)
-
- Mechanistic Studies on the Organocatalytic α-Chlorination of Aldehydes: The Role and Nature of Off-Cycle Intermediates
-
Herein we report the isolation and characterization of aminal intermediates in the organocatalytic α-chlorination of aldehydes. These species are stable covalent ternary adducts of the substrate, the catalyst and the chlorinating reagent. NMR-assisted kinetic studies and isotopic labeling experiments with the isolated intermediate did not support its involvement in downstream stereoselective processes as proposed by Blackmond. By tuning the reactivity of the chlorinating reagent, we were able to suppress the accumulation of rate-limiting off-cycle intermediates. As a result, an efficient and highly enantioselective catalytic system with a broad functional group tolerance was developed.
- Ponath, Sebastian,Menger, Martina,Grothues, Lydia,Weber, Manuela,Lentz, Dieter,Strohmann, Carsten,Christmann, Mathias
-
supporting information
p. 11683 - 11687
(2018/09/10)
-
- PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA AGONISTS, METHOD OF PREPARATION AND USES THEREOF
-
The present invention relates to new peroxisome proliferator-activated receptor gamma (PPAR?) agonists, and their uses as in the prevention and/or treatment of type 2 diabetes, impaired glucose tolerance, insulin resistance syndrome, hyperlipidemia, metabolic syndrome, visceral obesity, obesity, hyperlipidemia and hypertriglyceridemia. The preparation said compounds is also described.
- -
-
Page/Page column 24; 25
(2018/03/28)
-
- Synthesis of 4-N-α-coumaryl amino acids and investigation of their antioxidant, antimicrobial activities and fluorescence spectra
-
An efficient metal-free approach for the synthesis of N-coumaryl amino acids and the first one-step synthesis of 4-hydrazinocoumarin from 4-hydroxycoumarin was developed. The nucleophilic addition of amino acid methyl esters to 4-tosylcoumarins produced a series of 4-N-α-coumaryl amino acids in good to excellent yields without racemization. The antioxidant activities of the synthesized compounds were investigated using DPPH and FRAP methods. 4-Hydrazinocoumarin and N-coumaryl tyrosine had the best antioxidant activity. The antimicrobial activities of the compounds against Gram-positive was stronger than Gram-negative. 4-Hydrazinocoumarin showed the best antibacterial effect.
- Ghalehshahi, Hajar Golshadi,Balalaie, Saeed,Aliahmadi, Atousa,Moghimi, Roya
-
p. 1461 - 1470
(2018/08/03)
-
- Triterpene-amino acid derivative as well as preparation method and application thereof
-
The invention relates to application of a triterpene derivative in a formula in preparation of medicines for preventing or treating influenza diseases. The definition of substituent groups is shown ina description. The triterpene derivative has obvious inhibiting function on influenza viruses, and can obviously inhibit the influenza viruses from entering cells. The formula is shown in the description.
- -
-
Paragraph 0081
(2018/11/10)
-
- Ferrocene-modified amino acids: synthesis and in vivo bioeffects on hippocampus
-
A method for the ferrocene modification of amino acids of natural and synthetic origin has been developed. In the in vivo studies, the hippocampal electrical activity under the action of ferrocenyl(phenylpyrazolyl)glycine (1) was assessed. A meaningful rise (up to 25% compared to the control) in the response amplitudes of the focal potentials of the hippocampal region СА1 after intraperitoneal administration of compound 1 at the dose of 2.0 mg kg–1 was established.
- Rodionov,Snegur,Simenel,Dobryakova, Yu. V.,Markevich
-
p. 136 - 142
(2017/07/05)
-
- Chiral-pool synthesis of 1,2,4-trisubstituted 1,4-diazepanes as novel σ1 receptor ligands
-
Starting from enantiomerically pure amino acids, 1,4-diazepanes with various substituents in 1, 2, and 4-position were synthesized following the late stage diversification strategy. The key step in the formation of the seven-membered ring was the intramolecular EDC coupling of amino acids 15, 26, and 39. The configuration in 2-position does not influence the σ1 affinity and selectivity over related receptors. A cyclohexylmethyl or a butyl group are the preferred substituents in 4-position, whereas a methyl moiety in 2-position and a (substituted) benzyl moiety in 1-position result in the highest σ1 affinity. These results fit nicely to the reported σ1 pharmacophore models. The compounds did not inhibit the structurally related fungal enzyme sterol Δ8,7-isomerase, but showed inhibition of diverse enzymes in late cholesterol biosynthesis at high concentrations. In a screening against more than 50 target proteins, (2S)-1-benzyl-4-(4-methoxybenzyl)-2-methyl-1,4-diazepane ((S)-28b, Ki(σ1) = 0.86 nM) showed a clean receptor profile. The dose dependent potentiation of electrically stimulated contractions of guinea pig vas deferens indicates σ1 agonistic activity of (S)-28b. Even at a dose of 100 mg/kg (S)-28b did not induce severe toxic or behavioral effects in the Irwin screen. Clear cognition enhancing effects were observed for (S)-28b after inducing amnesia by scopolamine.
- Fanter, Lena,Müller, Christoph,Schepmann, Dirk,Bracher, Franz,Wünsch, Bernhard
-
supporting information
p. 4778 - 4799
(2017/10/05)
-
- Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators
-
Developing specific chemical functionalities to deploy in biological environments for targeted enzyme inactivation lies at the heart of mechanism-based inhibitor development but also is central to other protein-tagging methods in modern chemical biology including activity-based protein profiling and proteolysis-targeting chimeras. We describe here a previously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, α-(1′-fluoro)vinyl amino acids, bearing the side chains of the cognate amino acids. These are obtained by the capture of suitably protected amino acid enolates with β,β-difluorovinyl phenyl sulfone, a new (1′-fluoro)vinyl cation equivalent, and an electrophile that previously eluded synthesis, capture and characterization. A significant variety of biologically relevant AA side chains are tolerated including those for alanine, valine, leucine, methionine, lysine, phenylalanine, tyrosine, and tryptophan. Following addition/elimination, the resulting transoid α-(1′-fluoro)-β-(phenylsulfonyl)vinyl AA-esters undergo smooth sulfone-stannane interchange to stereoselectively give the corresponding transoid α-(1′-fluoro)-β-(tributylstannyl)vinyl AA-esters. Protodestannylation and global deprotection then yield these sterically encumbered and densely functionalized quaternary amino acids. The α-(1′-fluoro)vinyl trigger, a potential allene-generating functionality originally proposed by Abeles, is now available in a quaternary AA context for the first time. In an initial test of this new inhibitor class, α-(1′-fluoro)vinyllysine is seen to act as a time-dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei. The enantiomers of the inhibitor could be resolved, and each is seen to give time-dependent inactivation with this enzyme. Kitz-Wilson analysis reveals similar inactivation parameters for the two antipodes, L-α-(1′-fluoro)vinyllysine (Ki = 630 ± 20 μM; t1/2 = 2.8 min) and D-α-(1′-fluoro)vinyllysine (Ki = 470 ± 30 μM; t1/2 = 3.6 min). The stage is now set for exploration of the efficacy of this trigger in other PLP-enzyme active sites.
- McCune, Christopher D.,Beio, Matthew L.,Sturdivant, Jill M.,De La Salud-Bea, Roberto,Darnell, Brendan M.,Berkowitz, David B.
-
supporting information
p. 14077 - 14089
(2017/10/17)
-
- Chemical differentiation of three DMSP lyases from the marine: Roseobacter group
-
Dimethylsulfoniopropionate (DMSP) catabolism of marine bacteria plays an important role in marine and global ecology. The genome of Ruegeria pomeroyi DSS-3, a model organism from the Roseobacter group, harbours no less than three genes for different DMSP lyases (DddW, DddP and DddQ) that catalyse the degradation of DMSP to dimethyl sulfide (DMS) and acrylate. Despite their apparent similar function these enzymes show no significant overall sequence identity. In this work DddQ and DddW from R. pomeroyi and the DddP homolog from Phaeobacter inhibens DSM 17395 were functionally characterised and their substrate scope was tested using several synthetic DMSP analogues. Comparative kinetic assays revealed differences in the conversion of DMSP and its analogues in terms of selectivity and overall velocity, giving additional insights into the molecular mechanisms of DMSP lyases and into their putatively different biological functions.
- Burkhardt, Immo,Lauterbach, Lukas,Brock, Nelson L.,Dickschat, Jeroen S.
-
supporting information
p. 4432 - 4439
(2017/07/10)
-
- A method for preparing methyl valsartan
-
The invention provides a preparation method of valsartan. The preparation method has the technical effects that amide methyl ester and sodium azide are used as raw materials and are catalyzed by amine salt to carry out tetrazole formation reaction; side effects are minimized by controlling the reaction course; main products are furthest generated; unreacted raw materials are recycled and reused; the yield in the preparation method is increased by more than 10% relative to the yields in existing processes; compared with the existing processes, the method has the effect that plenty of high-toxicity wastewater is no longer generated, and is easy to be widely popularized industrially.
- -
-
Paragraph 0053-0054
(2017/08/25)
-
- Preparation and purification method of valsartan
-
The invention relates to the field of medicinal chemistry and discloses a preparation and purification method of valsartan. The method comprises the steps of (S1) adding L-valine and alcohol to a reaction kettle, slowly dropwise adding thionyl chloride, carrying out heating reflux reaction, adding isopropyl acetate for pulping, carrying out suction filtration to obtain an intermediate 1; (S2) carrying out nucleophilic reaction on the intermediate 1 and a starting material 2 in a solvent under an alkaline condition to obtain an intermediate 2; (S3) carrying out nucleophilic reaction on the intermediate 2 and valeryl chloride in the solvent under the alkaline condition to obtain an intermediate 3; and (S4) carrying out cyclization reaction on the intermediate 3, sodium azide and a catalyst ((-)-sparteine-Cu (II) complex) in the solvent, washing, crystallizing and drying to obtain the valsartan. The sodium azide and the catalyst ((-)-sparteine-Cu (II) complex) are used in the cyclization reaction, and the cyclization yield can reach 90%. According to the purification method, the purity of the raw materials of the valsartan is greater than 99.99%, the content of a solvent residue (ethyl acetate) is smaller than 0.5%, the content of a specific impurity is smaller than 0.1%, other unknown individual impurities are avoided and an enantiomer impurity is not detected.
- -
-
Paragraph 0070; 0071; 0072; 0073
(2017/10/13)
-
- Synthesis of the fungus metabolite cladosin C
-
Cladosin C is one of the few known enaminotetramic acids, isolated from extracts of the deep sea fungus Cladosporium sphaerospermum. It was synthesised in ten steps and 14% overall yield by a late-stage amination of the corresponding 3-acyltetramic acid. This was obtained by a Dieckmann condensation of an N-β-ketoacylaminoester derived from dehydrovalinate and the thioester-terminated side chain containing the stereogenic centre which stemmed from poly-(R)-3-hydroxybutyrate.
- Linder, David,Schobert, Rainer
-
p. 7672 - 7677
(2017/09/27)
-
- Regiodivergent Enantioselective γ-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of α,α-Disubstituted α-Amino Acids and N,O-Acetal Derivatives
-
Phosphine-catalyzed regiodivergent enantioselective C-2- and C-4-selective γ-additions of oxazolones to 2,3-butadienoates have been developed. The C-4-selective γ-addition of oxazolones occurred in a highly enantioselective manner when 2-aryl-4-alkyloxazol-5-(4H)-ones were employed as pronucleophiles. With the employment of 2-alkyl-4-aryloxazol-5-(4H)-ones as the donor, C-2-selective γ-addition of oxazolones took place in a highly enantioselective manner. The C-4-selective adducts provided rapid access to optically enriched α,α-disubstituted α-amino acid derivatives, and the C-2-selective products led to facile synthesis of chiral N,O-acetals and γ-lactols. Theoretical studies via DFT calculations suggested that the origin of the observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic oxazolide and the electrophilic phosphonium intermediate.
- Wang, Tianli,Yu, Zhaoyuan,Hoon, Ding Long,Phee, Claire Yan,Lan, Yu,Lu, Yixin
-
supporting information
p. 265 - 271
(2016/01/25)
-
- Preparation of the optically pure N-methyl amino ester method and product
-
The invention belongs to the field of organic synthesis of amino acids and discloses a method for preparing optically pure N-methyl amino-acid ester. The method comprises the following steps of carrying out esterification reaction on amino acid as a starting raw material and aldehyde to form an imine intermediate, carrying out reductive amination in the presence of palladium carbon, and carrying out hydrogenation and debenzylation to finally synthesize optically pure N-methyl amino-acid ester. The method has the advantages of simplicity in method, mild reaction conditions and good adaptability and side chains of D-type or L-type amino acid do not need to be protected.
- -
-
Paragraph 0045-0047
(2017/04/13)
-
- Phenyl oxazole compound and in the preparation of medicine for the treatment of cancer the application of the
-
The invention provides two novel phenyloxazole compounds and application thereof to a medicament for preventing and treating cancers and further provides a preparation method of the two compounds. The two compounds provided by the invention can achieve effects of preventing and treating the cancers such as the cervical cancer, the colon cancer, the liver cancer and the breast cancer by inhibiting expression of a microRNA-21 cancer factor and inhibiting growth and migration of cancer cells. Meanwhile, a micromolecule medicament used by the invention is easy to obtain, low in price, stable in performance and convenient to store and transport.
- -
-
Paragraph 0019-0020; 0047-0049
(2017/05/05)
-
- Phosphoramidate protides of five flavones and their antiproliferative activity against HepG2 and L-O2 cell lines
-
A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 μmol/L, 5.5 μmol/L and 6.6 μmol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells.
- Li, Yue-Qing,Yang, Fei,Wang, Liu,Cao, Zhi,Han, Tian-Jiao,Duan, Zhe-Ang,Li, Zhen,Zhao, Wei-Jie
-
p. 196 - 208
(2016/05/02)
-
- Mechanochemical Encapsulation of Fullerenes in Peptidic Containers Prepared by Dynamic Chiral Self-Sorting and Self-Assembly
-
Molecular capsules composed of amino acid or peptide derivatives connected to resorcin[4]arene scaffolds through acylhydrazone linkers have been synthesized using dynamic covalent chemistry (DCC) and hydrogen-bond-based self-assembly. The dynamic character of the linkers and the preference of the peptides towards self-assembly into β-barrel-type motifs lead to the spontaneous amplification of formation of homochiral capsules from mixtures of different substrates. The capsules have cavities of around 800 ?3 and exhibit good kinetic stability. Although they retain their dynamic character, which allows processes such as chiral self-sorting and chiral self-assembly to operate with high fidelity, guest complexation is hindered in solution. However, the quantitative complexation of even very large guests, such as fullerene C60 or C70, is possible through the utilization of reversible covalent bonds or the application of mechanochemical methods. The NMR spectra show the influence of the chiral environment on the symmetry of the fullerene molecules, which results in the differentiation of diastereotopic carbon atoms for C70, and the X-ray structures provide unique information on the modes of peptide-fullerene interactions.
- Szymański, Marek,Wierzbicki, Micha?,Gilski, Miros?aw,J?drzejewska, Hanna,Sztylko, Marcin,Cmoch, Piotr,Shkurenko, Aleksander,Jaskólski, Mariusz,Szumna, Agnieszka
-
supporting information
p. 3148 - 3155
(2016/03/23)
-
- Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents
-
A series of novel phosphoramidate derivatives of coumarin have been designed and synthesized as chitin synthase (CHS) inhibitors. All the synthesized compounds have been screened for their chitin synthase inhibition activity and antimicrobial activity in vitro. The bioactive assay manifested that most of the target compounds exhibited good efficacy against CHS and a variety of clinically important fungal pathogens. In particular, compound 7t with IC50 of 0.08 mM against CHS displayed stronger efficiency than the reference Polyoxin B with IC50 of 0.16 mM. In addition, the apparent Ki values of compound 7t was 0.096 mM while the Km of Chitin synthase prepared from Candida tropicalis was 3.86 mM for UDP-Nacetylglucosamine, and the result of the Ki showed that the compounds was a non-competitive inhibitor of the CHS. As far as the antifungal activity is concerned, compounds 7o, 7r and 7t were highly active against Aspergillus flavus with MIC values in the range of 1 μg/mL to 2 μg/Ml while the results of antibacterial screening showed that these compounds have negligible actions to the tested bacteria. These results indicated that the design of these compounds as antifungal agents was rational.
- Ji, Qinggang,Ge, Zhiqiang,Ge, Zhixing,Chen, Kaizhi,Wu, Hualong,Liu, Xiaofei,Huang, Yanrong,Yuan, Lvjiang,Yang, Xiaolan,Liao, Fei
-
p. 166 - 176
(2015/12/04)
-
- Catalysts and temperature driven melt polycondensation reaction for helical poly(ester-urethane)s based on natural L-amino acids
-
Catalyst and temperature driven melt polycondensation reaction was developed for natural L-amino acid monomers to produce new classes of poly(ester-urethane)s. Wide ranges of catalysts from alkali, alkali earth metal, transition metal and lanthanides were developed for the condensation of amino acid monomers with diols to yield poly(ester-urethane)s. A-B Diblock and A-B-A triblock species were obtained by carefully choosing mono- or diols in model reactions. More than two dozens of transition metal and lanthanide catalysts were identified for the polycondensation to yield high molecular weight poly(ester-urethane)s. Theoretical studies revealed that the carbonyl carbon in ester possessed low electron density compared to the carbonyl carbon in urethane which driven the thermo-selective polymerization process. Optical purity of the L-amino acid residues in the melt polycondensation process was investigated using D- and L-isomers and the resultant products were analyzed by chiral-HPLC and CD spectroscopy. CD analysis revealed that the amino acid based polymers were self-assembled as β-sheet and polyproline type II secondary structures. Electron and atomic force microscopic analysis confirmed the formation of helical nano-fibrous morphology in poly(ester-urethane)s. The newly developed melt polycondensation process is very efficient and optimized for wide range of catalysts to produce diverse polymer structures from natural L-amino acids.
- Anantharaj, Santhanaraj,Jayakannan, Manickam
-
p. 1065 - 1077
(2016/03/12)
-
- Gossypol with Hydrophobic Linear Esters Exhibits Enhanced Antitumor Activity as an Inhibitor of Antiapoptotic Proteins
-
A series of gossypol Schiff bases that were derived from unnatural linear amino acid methyl esters were identified and found to be much more potent than gossypol and ABT-199 in terms of anticancer activity. This is the first example of gossypol Schiff bases with increased activity. The investigation of the Schiff base side chain of gossypol revealed that the unique anticancer effect was achieved by the introduction of hydrophobic ester groups. The optimized products showed low micromolar pan antitumor activities against NCI-60 tumor cell lines, which is promising for further drug development. Studies on the preliminary mechanism of action for their cellular activities was also carried out with antiapoptotic protein (Bcl-2 and Mcl-1) inhibition FP assays. The molecular modeling analysis demonstrated a possible binding mode for these compounds with Bcl-2, which could explain the binding affinity of the novel gossypol Schiff bases with these proteins.
- Lu, Yuzhi,Wu, Shuangchan,Yue, Yuan,He, Si,Li, Jun,Tang, Jun,Wang, Wei,Zhou, Hai-Bing
-
supporting information
p. 1185 - 1190
(2016/12/18)
-
- Selective oxidation of amines to aldehydes or imines using laccase-mediated bio-oxidation
-
An efficient and practical chemo-enzymatic aerobic oxidation in water of benzylamines to obtain aldehydes or imines is described. Laccase from Trametes versicolor was chosen as biocatalyst, and TEMPO (radical 2,2,6,6-tetramethylpiperidine 1-oxyl) as mediator. A study on the pH dependence of the aqueous medium allowed us to realise a fine tuning on product selectivity. Under our optimized reaction conditions, the bio-oxidation of a series of primary, secondary and cyclic amines has been achieved.
- Galletti, Paola,Funiciello, Federica,Soldati, Roberto,Giacomini, Daria
-
p. 1840 - 1848
(2015/06/02)
-
- PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF
-
This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
- -
-
Page/Page column 130
(2015/07/07)
-
- Organometallic Complexes of Bulky, Optically Active, C 3-Symmetric Tris(4 S -isopropyl-5,5-dimethyl-2-oxazolinyl)phenylborate (ToP)
-
A bulky, optically active monoanionic scorpionate ligand, tris(4S-isopropyl-5,5-dimethyl-2-oxazolinyl)phenylborate (ToP), is synthesized from the naturally occurring amino acid l-valine as its lithium salt, Li[ToP] (1). That compound is readily converted to the thallium complex Tl[ToP] (2) and to the acid derivative H[ToP] (3). Group 7 tricarbonyl complexes ToPM(CO)3 (M = Mn (4), Re (5)) are synthesized by the reaction of MBr(CO)5 and Li[ToP] and are crystallographically characterized. The νCO bands in their infrared spectra indicate that π back-donation in the rhenium compounds is greater with ToP than with non-methylated tris(4S-isopropyl-2-oxazolinyl)phenylborate (ToP). The reaction of H[ToP] and ZnEt2 gives ToPZnEt (6), while ToPZnCl (7) is synthesized from Li[ToP] and ZnCl2. The reaction of ToPZnCl and KOtBu followed by addition of PhSiH3 provides the zinc hydride complex ToPZnH (8). Compound 8 is the first example of a crystallographically characterized optically active zinc hydride. We tested its catalytic reactivity in the cross-dehydrocoupling of silanes and alcohols, which provided Si-chiral silanes with moderate enantioselectivity (Chemical Equation).
- Xu, Songchen,Magoon, Yitzhak,Reinig, Regina R.,Schmidt, Bradley M.,Ellern, Arkady,Sadow, Aaron D.
-
p. 3508 - 3519
(2015/08/06)
-
- Synthesis, toxicity and chemo-sensitization of HeLa cells to etoposide, of some 2-methyl amino acid ester-substituted-1,3-benzoxazines
-
A number of new L- or LD-2-amino acid ester-(substituted)-benz[1,3]oxazines 12-17 were synthesized from the reaction of free L- or LD-amino acid ester 9a-d with 2-methylthio-1,3-benzoxazines 11a-g. The structures of the new products 12-17 were confirmed from their 1H, 13CNMR and IR spectra and CHN microanalysis. Some of these compounds weakly inhibited DNA-PK and platelet aggregation. Studies of the toxicity for some of the new compounds showed mostly no inhibitory effects on HeLa cell growth at 1 and 10 μM and some up to 40 μM. The chemo-sensitization to etoposide by some of the compounds revealed that the most effective chemo-sensitizers at 10 μM were 14c (1.83 fold), 12e (1.42 fold), 15a (0.8 fold), 16d (0.76 fold) and 1c (0.74). However, at 1 μM in the presence of etoposide, some compounds were shown to be more effective. No direct link was observed between the type of the L-amino acid methyl ester as well as the 7-, 8-, or 7, 8-substitution on the aromatic ring on the effectiveness of the chemo-sensitizers; however, the 7-hydroxy group did lower the effective chemo-sensitizers values.
- Ihmaid, Saleh K.,Fitzgibbon, Cheree,Al-Rawi, Jasim M. A.
-
p. 2825 - 2837
(2015/02/19)
-
- Fragmentation-Rearrangement of Peptide Backbones Mediated by the Air Pollutant NO2.
-
The fragmentation-rearrangement of peptide backbones mediated by nitrogen dioxide, NO2., was explored using di-, tri-, and tetrapeptides 8-18 as model systems. The reaction, which is initiated through nonradical N-nitrosation of the peptide bond, shortens the peptide chain by the expulsion of one amino acid moiety with simultaneous fusion of the remaining molecular termini through formation of a new peptide bond. The relative rate of the fragmentation-rearrangement depends on the nature of the amino acids and decreases with increasing steric bulk at the α carbon in the order Gly>Ala>Val. Peptides that possessed consecutive aromatic side chains only gave products that resulted from nitrosation of the sterically less congested N-terminal amide. Such backbone fragmentation-rearrangement occurs under physiologically relevant conditions and could be an important reaction pathway for peptides, in which sections without readily oxidizable side chains are exposed to the air pollutant NO2.. In addition to NO2.-induced radical oxidation processes, this outcome shows that ionic reaction pathways, in particular nitrosation, should be factored in when assessing NO2. reactivity in biological systems.
- Gamon, Luke F.,Nathanael, Joses G.,Taggert, Bethany I.,Henry, Fraser A.,Bogena, Jana,Wille, Uta
-
supporting information
p. 14924 - 14930
(2015/10/20)
-
- Efficient asymmetric addition of diethylzinc to aldehydes using C 2-novel chiral pyridine β-amino alcohols as chiral ligands
-
A series of novel C2-symmetric chiral pyridine β-amino alcohol ligands have been synthesized from 2,6-pyridine dicarboxaldehyde, m-phthalaldehyde and chiral β-amino alcohols through a two-step reaction. All their structures were characterized by 1H NMR, 13C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2R)-2,2-((pyridine-2,6-diylbis(methylene)) bisazanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was used in toluene at room temperature. The ligand 3g (2S,2R)-2,2-((1,3-phenylenebis(methylene)) bis(azanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright
- Zhang, Weijie,Tang, Ruiren,Yu, Huirong,Gao, Shu
-
p. 545 - 551
(2014/07/07)
-
- Synthesis of enantiomerically enriched indolines and tetrahydroisoquinolines from (S)-amino acid-derived chiral carbocations: An easy access to (3S,4R)-demethoxy-3-isopropyl diclofensine
-
Enantiomerically enriched indolines and tetrahydroisoquinolines were synthesized within 5 min to 2 h in high yields from easily accessible (S)-amino acid derived chiral carbocations. The diastereoselective Friedel-Crafts reaction is promoted by a Lewis acid (AlCl3) offering trans-diastereoselectivity. The rate of the reaction and diastereoselectivity of the product are significantly influenced by steric hindrance of the amino acids substituents and aryl groups. The methodology can be applied for the synthesis of the enantiomerically enriched bioactive scaffold (3S,4R)-demethoxy-3-isopropyl diclofensine. This journal is
- Manna, Sudipta Kumar,Panda, Gautam
-
p. 8318 - 8324
(2015/01/09)
-
- C-5′-substituted cinchona alkaloid derivatives catalyse the first highly enantioselective dynamic kinetic resolutions of azlactones by thiolysis
-
The highly enantioselective dynamic kinetic resolution (DKR) of azlactones by thiolysis has been achieved for the first time. Although both the parent alkaloid quinine and known C-5′-urea derivatives fail to promote the reaction effectively, a new class of C-5′-hydroxylated catalysts proved capable of catalysing the DKR of a range of azlactones derived from both unbranched- and, previously challenging, branched-chain amino acids in 84-92 % ee, including an example of the synthesis of an enantioenriched N-protected thioester derived from an extraterrestrial amino acid isolated from the Murchison meteorite. The highly enantioselective dynamic kinetic resolution (DKR) of azlactones by thiolysis has been achieved for the first time. Although both the parent alkaloid quinine and known C-5′-urea derivatives fail to promote the reaction effectively, a new class of C-5′-hydroxylated catalysts proved capable of catalysing the DKR of a range of azlactones in 84-92 % ee. Copyright
- Palacio, Carole,Connon, Stephen J.
-
supporting information
p. 5398 - 5413
(2013/09/02)
-
- Substituted 2-hydroxy-N-(arylalkyl)benzamides induce apoptosis in cancer cell lines
-
Variously substituted 2-hydroxy-N-(arylalkyl)benzamides were prepared and screened for antiproliferative and cytotoxic activity in cancer cell lines in vitro. Five compounds, out of 33 showed single-digit micromolar IC50 values against several human cancer cell lines. One of the most potent compounds N-((R)-1-(4-chlorophenylcarbamoyl)-2-phenylethyl)-5-chloro-2-hydroxybenzamide (6k) reduced proliferation and induced apoptosis in the melanoma cell line G361 in a dose-dependent manner, as shown by decrease in 5-bromo-2′- deoxyuridine incorporation and increase in several apoptotic markers, including subdiploid population increase, activation of caspases and site-specific poly-(ADP-ribose)polymerase (PARP) cleavage.
- Imramovsky, Ale?,Jorda, Radek,Pauk, Karel,?ezní?ková, Eva,Du?ek, Jan,Hanusek, Ji?í,Kry?tof, Vladimír
-
p. 253 - 259
(2013/10/01)
-
- Molecular architectonics of stereochemically constrained π-complementary functional modules
-
The elucidation of the complex factors that govern recognition events at the molecular level represents a daunting challenge in our quest to master the art of pre-programmed molecular assemblies. In this context, we present the molecular architectonics of thoughtfully designed amino acid appended functional molecules 1-5. Naphthalenediimide (NDI and pyrene were employed as functional modules due to their unusual topological shape similarity as well as complementary π-acidic and π-basic character, respectively. In addition, we show that dyads of such unusual functional modules energetically favour alternate assembly in contrast to the predominant self-sorted assembly observed for single-component systems. Moreover, by incorporating minute structural mutations into the amino acid side-chains of 1-5, we successfully tailored their assemblies into well-defined supramolecular architectures, namely supercoiled helices, twisted nanoribbons, nanobelts, comb-edged nanoflakes and nanosheets. A detailed analysis with the aid of experimental and theoretical studies has generated interesting insights into the factors that govern the recognition events at the molecular level. In a quest to master pre-programmed molecular assemblies, we show that alternate stacking over self-sorting of functional aromatic modules can be energetically controlled by smarter molecular design. Furthermore, by introducing structural mutations into the side-chain of amino acid auxiliaries, the molecular assemblies form tailored well-defined 1D and 2D supramolecular nanoarchitectures. Copyright
- Avinash,Samanta, Pralok K.,Sandeepa,Pati, Swapan K.,Govindaraju
-
p. 5838 - 5847
(2013/09/23)
-
- Cycloforskamide, a cytotoxic macrocyclic peptide from the sea slug Pleurobranchus forskalii
-
A macrocylic dodecapeptide, cycloforskamide, was isolated from the sea slug Pleurobranchus forskalii, collected off Ishigaki Island, Japan. Its planar structure was deduced by extensive NMR analyses and was further confirmed by MS/MS fragmentation analyses. Finally, the absolute configuration was determined by total hydrolysis and chiral-phase gas chromatographic analysis. This novel dodecapeptide contains three d-amino acids and three thiazoline heterocycles and exhibits cytotoxicity against murine leukemia P388 cells, with an IC 50 of 5.8 μM.
- Tan, Karen Co,Wakimoto, Toshiyuki,Takada, Kentaro,Ohtsuki, Takashi,Uchiyama, Nahoko,Goda, Yukihiro,Abe, Ikuro
-
p. 1388 - 1391
(2013/08/23)
-
- The synthesis and biological testing of bacilysin analogues
-
A series of compounds based on the structure of bacilysin were synthesised and tested for antibacterial activity. The key steps in the syntheses are the coupling of an iodide to a diketopiperazine (DKP) and mono-lactim ether scaffold, respectively. The diastereoselectivity of the coupling reactions was dependant on the scaffold, with selectivity for DKP of about 4:1 and mono-lactim ether exceeding 98:2. Subsequent elaboration of the compounds to give open chain dipeptides and DKPs that mimic the structure of bacilysin but substitute the epoxy ketone for a saturated or unsaturated ketone is described. Overall yield from coupling to final product was between 5 and 21 %, with the yield of the saturated products notably higher. The open chain dipeptides demonstrated moderate antibacterial and antifungal activity.
- Robertson, Keith,Murphy, Cormac D.,Paradisi, Francesca
-
p. 1157 - 1168
(2013/11/06)
-
