cas 3417-91-2, Methyl L-tyrosinate hydrochloride

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SYHTHESIS OF 2- AND 3-FLUOROTYROSINE WITH DILUTE FLUORINE GAS
Differences in reactivity and selectivity of fluorine gas towards L-tyrosine and the O,N-diacetylated derivative of L-tyrosine methyl ester have been exploited for the synthesis of 2- and 3-fluorotyrosine.Both 2- and 3-fluorotyrosine were identified by 2H, 19F and 13C NMR spectroscopy and high resolution mass spectrometry.The short synthesis time and high reaction yields allow this procedure to be used for the incorporation of the short lived positron emitting radionuclide 18F into the aromatic ring of L-tyrosine.
Chirakal, R.,Brown, K. L.,Firnau, G.,Garnett, E. S.,Hughes, D. W.,et al.
p. 267 - 278
(1987)
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Polystyrene or Magnetic Nanoparticles as Support in Enantioselective Organocatalysis? A Case Study in Friedel-Crafts Chemistry
Heterogenized versions of the second-generation MacMillan imidazolidin-4-one are described for the first time. This versatile organocatalyst has been supported on 1% DVB Merrifield resin and Fe3O4 magnetic nanoparticles through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The resulting catalytic materials have been successfully applied to the asymmetric Friedel-Crafts alkylation of indoles with α,β-unsaturated aldehydes. While both catalytic systems can be easily recovered and admit repeated recycling, the polystyrene-based catalyst shows higher stability and provides better stereoselectivities.
Ranjbar, Sara,Riente, Paola,Rodríguez-Escrich, Carles,Yadav, Jagjit,Ramineni, Kishore,Pericàs, Miquel A.
p. 1602 - 1605
(2016)
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RETRACTED ARTICLE: Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid for colon-specific drug delivery in inflammatory bowel disease
Mutual azo prodrug of 5-aminosalicylic acid with l-tyrosine was synthesized by coupling l-tyrosine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in rat fecal matter showed 87.18% release of 5-aminosalicylic acid with a half-life of 140.28 min, following first order kinetics. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. Myeloperoxidase activity was determined by the method of Krawisz et?al. The synthesized prodrug was found to produce comparable mitigating effect as that of sulfasalazine on colitis in rats.
Dhaneshwar, Suneela S.,Kandpal, Mini,Vadnerkar, Gaurav,Rathi, Badal,Kadam
p. 885 - 890
(2007)
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Enhancement of the Anti-Inflammatory Activity of NSAIDs by Their Conjugation with 3,4,5-Trimethoxybenzyl Alcohol
The synthesis of derivatives of three nonspecific COX-1 and COX-2 inhibitors, ibuprofen, ketoprofen, naproxen is presented. These acids were connected via an amide bond with an amino acid (L-proline, L-tyrosine, and beta-alanine) used as a linker. The amino acid carboxylic group was esterified with 3,4,5 trimethoxybenzyl alcohol. The activity of the novel derivatives was examined in vivo on carrageenan-induced inflammation, and in vitro, as cyclooxygenase and lipoxygenase inhibitors. It was found that the new compounds were more potent anti-inflammatory agents than the parent drugs. Thus, the ibuprofen (21) and ketoprofen (16) derivatives reduced rat paw edema by 67 and 91% (the reduction by the relevant NSAIDs was 36 and 47%, respectively). They inhibited COX-2 more than the starting drugs (21 by 67%, ibuprofen 46%, 19 by 94%, ketoprofen 49%). Docking of compounds on the active sites of COX-1 and COX-2 reflects their in vitro activity. Thus, 19 adopts an unfavorable orientation for COX-1 inhibition, but it binds effectively in the binding pocket of COX-2, in agreement with the absence of activity for COX-1 and the high inhibition of COX-2. In conclusion, the performed structural modifications result in the enhancement of the anti-inflammatory activity, compared with the parent NSAIDs.
Drouza, Chryssoula,Papagiouvannis, Georgios,Petrou, Anthi,Rekka, Eleni A.,Theodosis-Nobelos, Panagiotis,Tziona, Paraskevi
(2022/04/09)

PROCESS FOR MAKING BIARYL-BRIDGED CYCLIC PEPTIDES
The invention provides a method of preparing a biaryl-bridged cyclic peptide compound of Formula (I), where R1, R2, R3, R4, R5, R8, R7, R8, R9, R10, R11, R12, n and m are as defined in the specification. The biaryl-bridged cyclic peptides of Formula (I) are used in the preparation of pharmaceutically active substances, such as, for example, arylomycin and arylomycin analogues.
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Page/Page column 100

(2021/06/04)

Preparation method of L-tyrosine derivative
The invention discloses a preparation method of an L-tyrosine derivative. The L-tyrosine derivative is O-alkyl-N-[fluorenylmethoxycarbonyl]-L-tyrosine, L-tyrosine is used as a starting material, the O-alkyl-N-[fluorenylmethoxycarbonyl]-L-tyrosine is prepared through esterification, amidation, etherification/hydrolysis and amidation in sequence, the total yield of the target product can reach 61.5%, and the ee value can reach 99% or above. The preparation method disclosed by the invention has the advantages of cheap and easily available raw materials, lower cost and the like, for example, separation of triphenylphosphine oxide is avoided through etherification reaction. The method has the advantages of simple process, short route, mild reaction conditions and the like, for example, etherification and hydrolysis adopt a one-pot method; and the whole technological process generates few three wastes, the product yield and purity are high, and the method is suitable for industrial production.
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Paragraph 0034-0038; 0045-0047; 0054-0059; 0066-0071

(2021/06/09)

Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts
A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
Kervefors, Gabriella,Kersting, Leonard,Olofsson, Berit
supporting information
p. 5790 - 5795
(2021/03/08)

Transition-metal ion-mediated morphological transformation of pyridine-based peptide nanostructures
Inspired by natural metallopeptides, we have rationally designed two pyridine-conjugated short peptides. These two peptide conjugates formed a pair of constitutional isomers that helped us describe their structure-function relationship. Both the isomers consisted of an equal number of aromatic amino acid residues, but shuffling was observed in the position of two key amino acids, viz; tyrosine and phenylalanine, which brought a remarkable change in their self-assembling behavior. The presence of specific functional groups and chemical diversity in both conjugates made them very active towards metal coordination. Both the constitutional isomers adopted different pathways of self-assembly, which could be further controlled or transformed by the use of transition metal ions. Interestingly, it was observed that the metal ions could precisely control the morphology of these metallopeptide nanostructures and make them more stable. Therefore, such artificial metallopeptides possess remarkable advantages over the natural counterparts primarily due to their tailor-made chemical structures.
Singh, Narendra,Singh, Ramesh,Sharma, Swati,Kesharwani, Khushboo,Joshi, Khashti Ballabh,Verma, Sandeep
supporting information
p. 153 - 161
(2021/01/11)

Tyrosine-Specific Modification via a Dearomatization-Rearomatization Strategy: Access to Azobenzene Functionalized Peptides
Azobenzene functionalized peptides are of great importance in photoresponsive biosystems and photopharmacology. Herein, we report an efficient approach to prepare azobenzene functionalized peptides through late-stage modification of tyrosine-containing peptides using a dearomatization-rearomatization strategy. This approach shows good chemoselectivity and site selectivity as well as sensitive group tolerance to various peptides. This method enriches the postsynthetic modification toolbox of peptides and has great potential to be applied in medicinal chemistry and chemical biology.
Cheng, Yulian,Cheng, Zhehong,Fang, Lijing,Li, Hongchang,Su, Wu,Wang, Pengxin,Wang, Rui,Wu, Chunlei,Zhou, Yimin
supporting information
p. 4137 - 4141
(2021/06/27)

Novel Mixed NOP/Opioid Receptor Peptide Agonists
The nociceptin/orphanin FQ (N/OFQ)/N/OFQ receptor (NOP) system controls different biological functions including pain and cough reflex. Mixed NOP/opioid receptor agonists elicit similar effects to strong opioids but with reduced side effects. In this work, 31 peptides with the general sequence [Tyr/Dmt1,Xaa5]N/OFQ(1-13)-NH2 were synthesized and pharmacologically characterized for their action at human recombinant NOP/opioid receptors. The best results in terms of NOP versus mu opioid receptor potency were obtained by substituting both Tyr1 and Thr5 at the N-terminal portion of N/OFQ(1-13)-NH2 with the noncanonical amino acid Dmt. [Dmt1,5]N/OFQ(1-13)-NH2 has been identified as the most potent dual NOP/mu receptor peptide agonist so far described. Experimental data have been complemented by in silico studies to shed light on the molecular mechanisms by which the peptide binds the active form of the mu receptor. Finally, the compound exerted antitussive effects in an in vivo model of cough.
Pacifico, Salvatore,Albanese, Valentina,Illuminati, Davide,Marzola, Erika,Fabbri, Martina,Ferrari, Federica,Holanda, Victor A.D.,Sturaro, Chiara,Malfacini, Davide,Ruzza, Chiara,Trapella, Claudio,Preti, Delia,Lo Cascio, Ettore,Arcovito, Alessandro,Della Longa, Stefano,Marangoni, Martina,Fattori, Davide,Nassini, Romina,Calò, Girolamo,Guerrini, Remo
supporting information
p. 6656 - 6669
(2021/06/25)

Solvent-freeN-Boc deprotection byex situgeneration of hydrogen chloride gas
An efficient, scalable and sustainable method for the quantitative deprotection of thetert-butyl carbamate (N-Boc) protecting group is described, using down to near-stoichiometric amounts of hydrogen chloride gas in solvent-free conditions. We demonstrate theex situgeneration of hydrogen chloride gas from sodium chloride and sulfuric acid in a two-chamber reactor, introducing a straightforward method for controlled and stoichiometric release of HCl gas. The solvent-free conditions allow deprotection of a wide variety ofN-Boc derivatives to obtain the hydrochloride salts in quantitative yields. The procedure obviates the need for any work-up or purification steps providing an uncomplicated green alternative to standard methods. Due to the solvent-free, anhydrous conditions, this method shows high tolerance towards acid sensitive functional groups and furnishes expanded functional group orthogonality.
De Borggraeve, Wim M.,Gilles, Philippe,Van Mileghem, Seger,Verschueren, Rik H.
supporting information
p. 5782 - 5787
(2021/07/12)

NovelN-transfer reagent for converting α-amino acid derivatives to α-diazo compounds
A novel universalN-transfer reagent for direct and effective transformation of α-amino ketones, acetamides, and esters to the corresponding α-diazo products under mild basic conditions has been developed. This one-step synthetic approach not only allows for generation of α-substituted-α-diazo carbonyl compounds from α-amino acid derivatives but also permits preparation of α-diazo dipeptides fromN-terminal dipeptides (32 examples, up to 91%).
Lu, Guan-Han,Huang, Tzu-Chia,Hsueh, Hsiao-Chin,Yang, Shin-Cherng,Cho, Ting-Wei,Chou, Ho-Hsuan
supporting information
p. 4839 - 4842
(2021/05/25)

N-transfer reagent and method for preparing the same and its application
Provided are a novel N-transfer reagent and a method for preparing the same and its application. The N-transfer reagent is represented by the following Formula (I): The various novel N-transfer reagents of the present invention can be quickly prepared by employing different nitrobenzene precursors. The N-transfer reagents can directly convert a variety of amino compounds into diazo compounds under mild conditions. Particularly, the N-transfer reagents can facilitate the synthesis of the diazo compounds. The application of synthesizing diazo compounds of the present invention can greatly decrease the difficulty in operation, increase the safety during experiments, reduce the cost of production and the environmental pollution, and enhance the industrial value of diazo compounds.
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Page/Page column 24; 49-50; 55-56

(2021/06/25)

(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative as well as preparation method and application thereof
The invention discloses a (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative shown as a formula (I) or an optical isomer, a diastereomer and racemate mixture and pharmaceutically acceptable salt thereof as well as a preparation method and application of the (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative. It is shown by comparison of results of a positive control group and a model group on lymphedema prevention experiments that the compound disclosed in the invention shows obvious anti-edema activity.
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Paragraph 0047; 0106-0110

(2021/02/10)

Nickel-catalyzed deallylation of aryl allyl ethers with hydrosilanes
An efficient and mild catalytic deallylation method of aryl allyl ethers is developed, with commercially available Ni(COD)2 as catalyst precursor, simple substituted bipyridine as ligand and air-stable hydrosilanes. The process is compatible with a variety of functional groups and the desired phenol products can be obtained with excellent yields and selectivity. Besides, by detection or isolation of key intermediates, mechanism studies confirm that the deallylation undergoes η3-allylnickel intermediate pathway.
Ding, Guangni,Fan, Sijie,Wang, Jingyang,Wang, Yu,Wu, Xiaoyu,Xie, Xiaomin,Yang, Liqun,Zhang, Zhaoguo
supporting information

(2021/09/28)

Immunoproteasome Inhibitor-Doxorubicin Conjugates Target Multiple Myeloma Cells and Release Doxorubicin upon Low-Dose Photon Irradiation
Proteasome inhibitors are established therapeutic agents for the treatment of hematological cancers, as are anthracyclines such as doxorubicin. We here present a new drug targeting approach that combines both drug classes into a single molecule. Doxorubicin was conjugated to an immunoproteasome-selective inhibitor via light-cleavable linkers, yielding peptide epoxyketone-doxorubicin prodrugs that remained selective and active toward immunoproteasomes. Upon cellular uptake and immunoproteasome inhibition, doxorubicin is released from the immunoproteasome inhibitor through photoirradiation. Multiple myeloma cells in this way take a double hit: immunoproteasome inhibition and doxorubicin-induced toxicity. Our strategy, which entails targeting of a cytotoxic agent, through a covalent enzyme inhibitor that is detrimental to tumor tissue in its own right, may find use in the search for improved anticancer drugs.
Dekker, Patrick M.,Florea, Bogdan I.,Maiorana, Santina,Maurits, Elmer,Neefjes, Jacques J. C.,Overkleeft, Herman S.,Van De Graaff, Michel J.,Van Der Zanden, Sabina Y.,Van Kasteren, Sander I.,Wander, Dennis P. A.
supporting information
p. 7250 - 7253
(2020/08/06)

Synthesis of Biaryl-Bridged Cyclic Peptides via Catalytic Oxidative Cross-Coupling Reactions
Biaryl-bridged cyclic peptides comprise an intriguing class of structurally diverse natural products with significant biological activity. Especially noteworthy are the antibiotics arylomycin and its synthetic analogue G0775, which exhibits potent activity against Gram-negative bacteria. Herein, we present a simple, flexible, and reliable strategy based on activating-group-assisted catalytic oxidative coupling for assembling biaryl-bridged cyclic peptides from natural amino acids. The synthetic approach was utilized for preparing a number of natural and unnatural biaryl-bridged cyclic peptides, including arylomycin/G0775 and RP 66453 cyclic cores.
Ben-Lulu, Mor,Gaster, Eden,Libman, Anna,Pappo, Doron
supporting information
p. 4835 - 4839
(2020/02/11)

Method for preparing Fmoc-Tyr (tBu)-OH
The invention relates to a method for preparing FmocTyr (tBu)-OH, and belongs to the technical field of medical intermediate chemical engineering. The technical problem to be solved by the invention is to provide a method for preparing Fmoc-Tyr (tBu)-OH with good safety. The method comprises the following steps: a, mixing an Fmoc-Tyr-OR solid, tert-butyl acetate, perchloric acid and tert-butyl alcohol to react, adjusting the pH value to 5-6, separating out a solid, filtering, washing and drying to obtain an Fmoc-Tyr (tBu)-OR solid, wherein R is a C1-C4 alkyl; and b, carrying out hydrolysis onthe Fmoc-Tyr (tBu)-OR solid to obtain an Fmoc-Tyr (tBu)-OH product. The method is improved on the basis of the existing synthetic route, isobutene is not added when tert-butyl is introduced, the operation is simple and controllable, the safety is good, the cost is low, the production steps can be effectively shortened, the production efficiency and the yield are improved, and the method is suitable for modern industrial production.
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Paragraph 0052-0053; 0062-0063; 0067-0068; 0072-0073; 0077

(2020/12/30)

Synthesis method of tirofiban hydrochloride intermediate III (by machine translation)
The invention belongs to the field, of medicine synthesis, and particularly relates to a synthesis method III of tirofiban hydrochloride intermediate. by, reduction of an intermediate I under the action of a sodium borohydride reducing system to obtain intermediate II, intermediate II under Lewis acid chloride in the presence. SOCl2 Reaction conditions of, process are mild III, and N - process operation is simple, the reaction conditions of the reaction yield, product are improved, the product purity is high, and the reaction yield is increased by, times without being subjected to column purification, to improve the clinical medication safety, of the injection using, the standard crude drug product of the pharmacopoeia standard, and is suitable, for industrial production. (by machine translation)
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Paragraph 0072-0073

(2020/06/02)

12-Hydroxy stearic acid appended new amphiphilic scaffolds for selective capture of hydrogen halides through supramolecular hydrogelation
12-Hydroxystearic acid (12-HSA) appended new amphiphilic scaffolds reveal excellent hydrogelation propensity in the presence of aqueous acids and vapors of HCl/HBr. This selective entrapment efficiency towards hydrogen halides demonstrates an unprecedented route for the successful removal of toxic chemicals, thus providing a safe and easy protocol for environment management. We anticipate that the halide derivative of the amphiphile plays a vital role in driving the self-assembly mechanism and eventually the hydrogelation phenomena.
Sharma, Ankita,Gupta, Arindam,Tiwari, Priyanka,Basu, Anindya,Duttkonar, Anita
p. 3828 - 3832
(2020/03/19)

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)

NOVEL TRF1 MODULATORS AND ANALOGUES THEREOF
Novel TRF1 modulators and analogues thereof. There is provided compounds of Formula I, wherein R, R1, R2 and X have meanings written in the description. Such compounds are useful as TRF1 inhibitors and, for that reason, as medicaments, in the treatment of cancer, particularly high cancer stem cell cancer like glioblastoma and lung cancer, and can be also useful for the development of additional TRF1 inhibitors and increasing knowledge about TRF1 activity.
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Paragraph 0053; 0164-0165; 0174-0175

(2020/03/26)

Total Synthesis of Herquline B and C
The total syntheses of (-)-herquline B (2) and a heretofore-unrecognized congener, (+)-herquline C (3), are described. The syntheses require 14 and 13 steps, respectively, and feature a key oxazoline reduction that sets the stage for piperazine construction.
Cox, Joshua B.,Kimishima, Aoi,Wood, John L.
supporting information
p. 25 - 28
(2019/01/16)

In search of bioinspired hydrogels from amphiphilic peptides: A template for nanoparticle stabilization for the sustained release of anticancer drugs
The development of potent stimuli-responsive hydrogels has rapidly expanded in the last decades due to their diversified applications in the field of biomedicines. In accordance with this drift, herein, we aimed at modulating a series of amphiphilic peptide analogues with the general formula Me-(CH2)14-CO-NH-CH(X)-COOH, where X = CH2Ph in hydrogelators I (l-Phe) and II (d-Phe) and X = CH2Ph(OH) in hydrogelator III (l-Tyr), which displayed an excellent propensity to immobilize water at room temperature with a minimum gelation concentration of 0.04%/0.05%/0.02% w/v for hydrogelators I-III, respectively, regardless of their configuration at the C-terminal centre. To validate this threshold concentration difference, we performed computational analysis that demonstrated the ability of the side-chains of hydrogelators I and III to remain highly planar with the methylene units of the amphiphile and aromatic rings, promoting favourable correspondence through van der Waals forces and pi-pi stacking. Consequently hydrogelators I and III self-assembled in an ordered organisation superior to hydrogelator II. Furthermore, the spectroscopic and microscopic experiments revealed that the hydrogelators manifested a β-sheet conformation and nanofibrous morphology at the supramolecular level. As observed visually and additionally confirmed by differential scanning calorimetry (DSC) and rheological measurements, the hydrogels exhibited thermo-reversibility, injectability and high mechanical strength. Importantly, these biomaterials were also found to be resistant towards proteolytic degradation and non-cytotoxic in the cell line HEK 293 using a dose-dependant cell viability assay. To date, the development of a structured approach for the release of drugs in a predictable manner from an optimised formulation, using peptide-based hydrogel nanoparticles as a delivery system remains in its infancy. Hence, we developed hydrogel nanoparticles (HNPs) with our fabricated amphiphilic peptides that exploited the weak noncovalent interactions for their fabrication, unlike other cross-linked polymers that require strong covalent or ionic bonds for their formation. Interestingly, the as-synthesized nanoparticles showed an unprecedented ability to release the anticancer drugs 5-fluoro uracil/doxorubicin at physiological conditions depending on the physico-chemical parameters of the drugs. We believe that the reported injectable, biocompatible, amphiphilic peptide-based hydrogels hold future promise as a potential tool to transport drugs to a targeted site at a greater concentration, thus relieving the patient from surgical injury and simultaneously aiding in a faster recovery.
Mehra, Radha Rani,Tiwari, Priyanka,Basu, Anindya,Duttkonar, Anita
p. 11666 - 11678
(2019/07/31)

Administration of ferrocene-modified amino acids induces changes in synaptic transmission in the CA1 area of the hippocampus
A series of ferrocene-modified amino acid methyl esters with pyrazole linker was prepared in good to quantitative yields starting from easy accessible ferrocene pyrazole carbaldehyde and amino acids in racemic and enantio enriched forms under reductive amination conditions (NaBH (OAc)3, reflux, 3 hr). The resulting enantiomers were resolved using analytical HPLC on modified cellulose or amylose as chiral selectors. In vivo electrophysiological experiments were performed in the CA1 field of the hippocampus on 3a Fc-Gly, (L)-3b Fc-Ala, and (D)-3b Fc-Ala compounds. An increasing in the amplitudes of responses of local potentials (up to 25%) of the CA1 region in the studied groups was found after intraperitoneal administration of ferrocene compounds 3a and (D)-3b compared with control rats treated with saline.
Dobryakova, Yulia V.,Ilyin, Mikhail M.,Markevich, Vladimir A.,Rodionov, Alexey N.,Simenel, Alexander A.,Snegur, Lubov V.
(2020/01/24)

Synthesis and biological evaluation of clovamide analogues with catechol functionality as potent Parkinson's disease agents in vitro and in vivo
In this study, seven clovamide analogues (1–7) were designed and synthesized, and the neuroprotection of 1–7 as well as 8–15 (prepared in our previous work) against H2O2-induced oxidative stress was evaluated in SH-SY5Y cells. Results showed that 1–7 with catechol groups exhibited better neuroprotective effects than 8–15, and their EC50 values ranged from 4.26 to 23.83 μM, especially 1, indicating that the moiety of catechol governed the activities of these compounds. Furthermore, oral administration of 1 (10 or 20 mg/kg) was demonstrated to possess anti-PD effect through alleviating apoptosis and oxidative stress in vitro and in vivo, and to up-regulate the expression of heme oxygenase-1 (HO-1) via PI3K/AKT/mTOR pathway. Finally, the pharmacokinetic (PK) assessment of 1 was determined in rats. These findings suggested that 1 might be an effective candidate for PD therapy.
Feng, Jia-Hao,Hu, Xiao-Long,Lv, Xian-Yu,Wang, Bao-Lin,Lin, Jun,Zhang, Xiao-Qi,Ye, Wen-Cai,Xiong, Fei,Wang, Hao
supporting information
p. 302 - 312
(2018/11/27)

Synthesis, CYP 450 evaluation, and docking simulation of novel 4-aminopyridine and coumarin derivatives
Four series of novel compounds based on 4-aminopyridine, glatiramer acetate, pyrone, and coumarin backbones were sufficiently synthesized and identified by spectroscopic methods. CYP enzyme inhibition assays of five predominate human P450 isozymes indicate that all compounds, except for 4-hydrazide pyridine 1c, seem to be less toxic than 4-aminopyridine. Further investigation of the compounds using molecular docking experiments revealed different, the same, or stronger binding modes for most of the synthesized compounds, with both polar and hydrophobic interactions with the 1WDA and 1J95 receptors compared to benzoyl l-arginine amide and 4-aminopyridine, respectively. These results introduce the synthesized compounds as K+ channel blockers that could be considered for in vivo CNS disease studies.
Ghalehshahi, Hajar G.,Balalaie, Saeed,Sohbati, Hamid R.,Azizian, Homa,Alavijeh, Mohammad S.
(2019/01/21)

Visible-Light-Induced [4+2] Annulation of Thiophenes and Alkynes to Construct Benzene Rings
The [4+2] annulation represents an elegant and versatile synthetic protocol for the construction of benzene rings. Herein, a strategy for visible-light induced [4+2] annulation of thiophenes and alkynes, to afford benzene rings, is presented. Under simple and mild reaction conditions, the ready availability and structural diversity of thiophenes and alkynes permit the facile synthesis of several substituted aromatic rings. Valuable drugs and amino acids are also well tolerated. Moreover, DFT calculations explain the high regioselectivity of the reaction.
Song, Chunlan,Dong, Xin,Wang, Zhongjie,Liu, Kun,Chiang, Chien-Wei,Lei, Aiwen
supporting information
p. 12206 - 12210
(2019/07/31)

Tuning the reaction pathways of phenanthroline-Schiff bases: Routes to novel phenanthroline ligands
Pyrido-phenanthrolin-7-one compounds are structural analogues of the cytotoxic alkaloid, ascididemin, and would be expected to have interesting biological activities. Synthetic strategies are reported for a novel simple route to form this class of ligand. 1,10-Phenanthrolin-5,6-dione reacts with l-phenylalanine alkyl esters and their para-substituted analogues to form both a phenanthroline-oxazine and a pyrido-phenanthrolin-7-one product. The nature of the major product is dependent on the electronic properties of the para substituent. Successful metal coordination to the pyrido-phenanthrolin-7-one ligand is also presented.
Ahmed, Muhib,Rooney, Denise,McCann, Malachy,Casey, Jamie,O'Shea, Katie,Twamley, Brendan
p. 15283 - 15289
(2019/10/22)

Selective Photoredox Trifluoromethylation of Tryptophan-Containing Peptides
For application in drug discovery and biomedicine, it is crucial to develop new biocompatible methods to modify polypeptides. Herein, a visible-light-induced photoredox trifluoromethylation of tryptophan-containing peptides is reported. Under a mild, biocompatible, and straightforward condition, this strategy could incorporate the trifluoromethyl group into tryptophan residue with excellent chemo- and site-selectivity. The use of lower photocatalyst loading in 2 mol-% and cheap CF3SO2Na salt represents a great catalytic activity and economic CF3 source. This direct trifluoromethylation strategy allows the ready study of fluorinated peptides exploiting 19F-NMR. Additionally, the development of this protocol enables the study of biochemical systems and potentially modulates the function of biomolecules. Careful mechanistic studies (Stern-Volmer fluorescence quenching, EPR, and radical inhibition/trapping experiments) indicate that the reaction would proceed with a radical–radical cross-coupling procedure.
Ding, Bo,Weng, Yue,Liu, Yunqing,Song, Chunlan,Yin, Le,Yuan, Jiafan,Ren, Yanrui,Lei, Aiwen,Chiang, Chien-Wei
p. 7596 - 7605
(2019/12/15)

((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-β-lactamase inhibitors: Synthesis, kinetic and crystallographic studies
The emergence and global spread of metallo-β-lactamase (MBL) mediated resistance to almost all β-lactam antibacterials poses a serious threat to public health. Since no clinically useful MBL inhibitors have been reported, there is an urgent need to develop new potent broad-spectrum MBL inhibitors effective against antibacterial resistance. Herein, we synthesized a set of 2-substituted ((S)-3-mercapto-2-methylpropanamido) acetic acid derivatives, some of which displayed potent inhibition with high ligand efficiency to the clinically relevant MBL subtypes, Verona Integron-encoded MBL (VIM)-2 and New Delhi MBL (NDM)-1. Kinetic studies revealed that the inhibitors are not strong zinc chelators in solution, and they bind reversibly to VIM-2 but dissociate very slowly. Crystallographic analyses revealed that they inhibit VIM-2 via chelating the active site zinc ions and interacting with catalytically important residues. Further cell- and zebrafish-based assays revealed that the inhibitors slightly increase susceptibility of E. coli cells expressing VIM-2 to meropenem, and they have no apparent toxicity to the viability of HEK293T cells and the zebrafish embryogenesis.
Liu, Sha,Jing, Li,Yu, Zhu-Jun,Wu, Chengyong,Zheng, Yongxiang,Zhang, En,Chen, Qiang,Yu, Yamei,Guo, Li,Wu, Yong,Li, Guo-Bo
p. 649 - 660
(2018/02/10)

Structure-activity relationship of clovamide and its related compounds for the inhibition of amyloid β aggregation
Alzheimer's disease (AD), a neurodegenerative disorder, is characterized by aggregation of amyloid β-protein (Aβ). Aβ aggregates through β-sheet formation and induces cytotoxicity against neuronal cells. Inhibition of Aβ aggregation by naturally occurring compounds is thus a promising strategy for the treatment of AD. We have already reported that caffeoylquinic acids and phenylethanoid glycosides, which possess two or more catechol moieties, strongly inhibited Aβ aggregation. Clovamide (1) containing two catechol moieties, isolated from cacao beans (Theobroma cacao L.), is believed to exhibit preventive effects on Aβ aggregation. To investigate the structure-activity relationship of clovamide (1) for the inhibition of Aβ aggregation, we synthesized 1 and related compounds 2–11 through reaction between L-DOPA, D-DOPA, L-tyrosine, or L-phenylalanine and caffeic acid, p-coumaric acid, or cinnamic acid, and compounds 12 and 13 were derived from 1. Among tested compounds 1–13, those containing one or two catechol moieties exhibited potent anti-aggregation activity, whereas the non-catechol-type related compounds showed little or no activity. This suggests that at least one catechol moiety is essential for inhibition of Aβ42 aggregation, and this activity increases depending on the number of catechol moieties. Consequently, clovamide (1) and its related compounds may be a promising therapeutic option for inhibiting Aβ-mediated pathology in AD.
Tsunoda, Tatsuhiko,Takase, Mio,Shigemori, Hideyuki
p. 3202 - 3209
(2018/05/05)

Tertiary-butoxycarbonyl (Boc) – A strategic group for N-protection/deprotection in the synthesis of various natural/unnatural N-unprotected aminoacid cyanomethyl esters
A number of cyanomethyl esters of natural/unnatural aminoacids with un-protected amino functionality were synthesized because of their synthetic and medicinal importance. Critical N-Boc deprotection methods in the presence of labile (hydrolytic sensitivity) cyanomethyl functionality were screened thoroughly and it was found that readily available 4M HCl in 1,4-dioxane solution (2–4 equiv); acetonitrile, 0 °C, 2–4 h was a suitable condition. This condition was generalized and successfully applied to a variety of alkyl, alkynyl, aryl, heteroaryl, benzyl, azido, spiro amino acid cyanomethylesters irrespective of the nature of the amine (primary or secondary) and the distance between the amine and ester group to achieve final deprotected amino esters with high yield, and purity compared to other commonly known N-protecting groups (Cbz, Fmoc, Ac, Bn, Bz etc.). It was also demonstrated that N-Boc protected aminoacid cyanomethylesters are stable enough to carry out further functionalization compared to N-unprotected counterparts.
Karmakar, Ananta,Basha, Mushkin,Venkatesh Babu,Botlagunta, Murali,Malik, Noormohamed Abdul,Rampulla, Richard,Mathur, Arvind,Gupta, Arun Kumar
supporting information
p. 4267 - 4271
(2018/11/03)

An auxin-tyrosine derivative based biocompatible supergelator: A template for fabrication of nanoparticles for sustained release of model drugs
Bioinspired self-assembling peptides serve as powerful building blocks in the manufacturing of nanomaterials with tailored features. Inspired by the supergelating ability of naphthyl-Phe-OH (hydrogelator I), we synthesized naphthyl-Tyr-OH (hydrogelator II) and naphthyl-Trp-OH (hydrogelator III) with the objective of exploring the propensities of the phenolic OH of Tyr and the NH of the indole for controlling the gelation process. However, our experimental investigation reveals that hydrogelator II, containing Tyr as the aromatic core, shows an excellent gelation ability. But the Trp analogue fails to do so under similar conditions. To validate our results we performed MD simulation in an aqueous environment which significantly justifies that hydrogelator II exhibits a better hydrogelation ability than hydrogelators I and III. The characterisation of hydrogelator II was then performed in detail using various analytical and microscopic techniques and its biocompatibility was tested using an MTT assay. To examine the potentiality of hydrogelator II in drug delivery we developed hydrogel nanoparticles (HNPs) using the concept of self-assembly entirely governed by an ecofriendly approach i.e. weak interactions (like H-bonding, π-π and hydrophobic interactions). Our hydrogel nanoparticles display good release kinetics of the model drugs 5-fluorouracil and curcumin from the hydrogel matrix depending on their chemical structure, molecular weight and hydrophobicity. Thus our research shows that the choice of the core residue has a profound impact on the self-assembly process and thus on the gelation properties. Moreover, nanoparticles generated from our novel biocompatible hydrogelator II hold promise for future drug delivery applications.
Tiwari, Priyanka,Basu, Anindya,Sahu, Sonu,Gound, Sadhna,Christman, Ryann M.,Tiwari, Amit K.,Trivedi, Piyush,DuttKonar, Anita
p. 4915 - 4922
(2018/03/30)

2',6'-dimethyltyrosine derivative and C-H activation methylation synthesis method thereof
The present invention provides a 2',6'-dimethyltyrosine derivative and a C-H activation methylation synthesis method thereof, specifically a compound represented by the following formula I, wherein each group is defined in the specification. The invention further provides a preparation method of the compound. The formula I is defined in the specification.
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Paragraph 0222 - 0224

(2018/04/01)

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)

Anti-parasite and cytotoxic activities of chloro and bromo L-tyrosine derivatives
A series of twenty-one L-tyrosine derivatives with modifications in the halogenation pattern of the aromatic ring and different degree of methylations on the amine and phenolic hydroxyl groups were synthesized. The structures of all the intermediates and target compounds were confirmed unambiguous by spectroscopy analysis. Additionally, all compounds were evaluated against Plasmodium falciparum and Leishmania panamensis parasites between 20-702 μg mL-1. The cytotoxic evaluation was done to determine the selectivity index for each compound. Six compounds had the lower EC50 (effective concentration 50) against L. panamensis. One of these compounds was the most active with an EC50 at 24.13 μg mL-1 (76.07 μM). All derivatives showed no significant activity against P. falciparum and no compound has in vitro antifungal activity at 500 μg mL-1.
Restrepo, Manuel Pastrana,Jaramillo, Elkin Galeano,Martínez, Alejandro Martínez,Arango, Ana Mesa,Restrepo, Sara Robledo
p. 2569 - 2579
(2018/11/06)

Synthesis and trypanocide activity of chloro-l-tyrosine and bromo-l-tyrosine derivatives
Twenty-two halogenated l-tyrosine derivatives were synthesized to examine new substances for the treatment of Chagas disease. The synthesis of these derivatives with different degree of substitution in the amino group with methyl iodide, giving primary, tertiary, and quaternary amino acids. All compounds were tested in vitro against intracellular amastigotes of Trypanosoma cruzi, and the cytotoxicity were evaluated over monocytic cell line U-937. Compound 25 was the most active against T. cruzi with a EC50 of 75.52 μM compared with benznidazole with a EC50 of 58.79 μM. Compounds 3, 4, 7, and 15 were the derivatives with the best selectivity index (SI) with values of 7.5, 8.3,12.1, and 8.6, respectively. Finally, compound 7 was the safer and the more promising derivative against T. cruzi.
Pastrana Restrepo, Manuel,Galeano Jaramillo, Elkin,Martínez Martínez, Alejandro,Robledo Restrepo, Sara
p. 2454 - 2465
(2018/10/02)

Tyrosine [...] hydrochloride, its synthetic method and use thereof (by machine translation)
The invention relates to a synthetic tyrosine [...] hydrochloride. In particular, the method comprises a) make the tyrosine to undergo esterification reaction, in order to get the ester intermediate 2; b) to the ester intermediate 2 in the protection of the amino and phenolic hydroxyl, to obtain the 3 compound; c) suitcase 3 in order to obtain a compound represented by 4 compound; d) oxidized type 4 to obtain the compound represented by the 5 compound; e) the formula 5 with a compound expressed as semicarbazide reaction, to obtain the 6 compound; f) the formula 6 compound represented deprotection, to obtain the 7 said tyrosine [...] hydrochloride; wherein R stands for methyl, ethyl or propyl; R1 As can be used to amino and phenolic hydroxyl protecting group. In addition, the invention also relates to the tyrosine [...] hydrochloride and its use. (by machine translation)
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Paragraph 0057; 0058; 0085

(2018/10/26)

Improved binding affinities of pyrrolidine derivatives as Mcl-1 inhibitors by modifying amino acid side chains
As an important member of anti-apoptotic Bcl-2 protein, myeloid cell leukemia sequence 1 (Mcl-1) protein is an attractive target for cancer therapy. In this study, a new series of pyrrolidine derivatives as Mcl-1 inhibitors were developed by mainly modifying the amino acid side chain of compound 1. Among them, compound 18 (Ki= 0.077 μM) exhibited better potent inhibitory activities towards Mcl-1 protein compared to positive control Gossypol (Ki= 0.18 μM). In addition, compound 40 possessed good antiproliferative activities against PC-3 cells (Ki= 8.45 μM), which was the same as positive control Gossypol (Ki= 7.54 μM).
Wan, Yichao,Liu, Tingting,Li, Xiaoxian,Chen, Chen,Fang, Hao
p. 138 - 152
(2016/12/22)

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)

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)

Step-Up Synthesis of Periodic Mesoporous Organosilicas with a Tyrosine Framework and Performance in Horseradish Peroxidase Immobilization
New amino-acid-bridged periodic mesoporous organosilicas (PMOs) were constructed by hydrolysis and condensation reactions under acid conditions in the presence of a template. The tyrosine bissilylated organic precursor (TBOS) was first prepared through a multistep reaction by using tyrosine (a natural amino acid) as the starting material. PMOs with the tyrosine framework (Tyr-PMOs) were constructed by simultaneously using TBOS and tetraethoxysilane as complex silicon sources in the condensation process. All the Tyr-PMOs materials were characterized by XRD, FTIR spectroscopy, N2 adsorption–desorption, TEM, SEM, and solid-state 29Si NMR spectroscopy to confirm the structure. The horseradish peroxidase (HRP) enzyme was first immobilized on these new Tyr-PMOs materials. Optimal conditions for enzyme adsorption included a temperature of 40 °C, a time of 8 h, and a pH value of 7. Furthermore, the novel Tyr-PMOs materials could store HRP for approximately 40 days and maintained the enzymatic activity, and the Tyr-PMOs–10 % HRP with the best immobilization effect could be reused at least eight times.
Wang, Jianqiang,Zhang, Wenqi,Gu, Changqing,Zhang, Wenpei,Zhou, Man,Wang, Zhiwei,Guo, Cheng,Sun, Linbing
supporting information
p. 3162 - 3171
(2017/11/22)

Method for synthesizing tyrosine framework type periodic mesoporous organosilicas materials
The invention relates to a method for preparing tyrosine framework type periodic mesoporous organosilicas materials. The method for synthesizing the tyrosine framework type periodic mesoporous organosilicas materials includes esterifying tyrosine in methanol by the aid of thionyl chloride; carrying out acrylation on the tyrosine by the aid of hydrazine hydrate and carrying out reaction on the tyrosine and isocyanic acid propyltriethoxysilane to obtain tyrosine organosilicas precursors; hydrolyzing the tyrosine organosilicas precursors and surfactants under acidic conditions to form PMO (periodic mesoporous organosilicas) materials; removing the surfactants from the PMO materials by means of extraction to ultimately form PMO materials with specific morphological structures. The tyrosine is used as a substrate. The methanol is used as a solvent. The method has the advantages synthesis reaction raw materials are simple and are easily available, synthesis operation is simple and convenient and is easy to implement, and the method is high in yield and low in energy consumption and is safe and inexpensive; the tyrosine framework type periodic mesoporous organosilicas materials prepared by the aid of the method have important application prospects in the fields of biosensors, catalyst carriers, adsorbents, sustained-release medicine capsules, chromatographic separation and the like.
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Paragraph 0024

(2017/08/29)

Pd-catalyzed dimethylation of tyrosine-derived picolinamide for synthesis of (S)-N-Boc-2,6-dimethyltyrosine and its analogues
A short and efficient synthesis of (S)-N-Boc-2,6-dimethyltyrosine utilizing palladium-catalyzed directed C-H functionalization is described. This represents the first general method for the ortho-dimethylation of tyrosine derivatives and offers a practical approach for preparing this synthetically important building block. Notably, throughout the reaction sequence no racemization occurs at the susceptible a-chiral centers.
Wang, Xuning,Niu, Songtao,Xu, Lanting,Zhang, Chao,Meng, Lingxing,Zhang, Xiaojing,Ma, Dawei
supporting information
p. 246 - 249
(2017/11/27)

Preparation method of alanine derivatives
The invention discloses a method for preparing alanine derivatives disclosed as Formula (I). The alanine derivatives can be used as a synthesis intermediate of an opioid receptor regulator, such as a synthesis intermediate of eluxadoline. By using the cheap and accessible chiral tyrosine as the initial raw material, the invention provides a brand-new synthesis route for preparing alanine derivatives. The whole reaction route has the advantages of high total yield, low cost and mild reaction conditions, is simple and safe for operation, and is suitable for large-scale industrial production.
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Paragraph 0073; 0074; 0075

(2016/10/08)

Hydrogel supported chiral imidazolidinone for organocatalytic enantioselective reduction of olefins in water
Chiral products play an important role particularly in the field of medicinal chemistry, where it is known that enantiomers often have very different biological properties and effects. One of the most powerful tool to obtain a product as a single enantiomer is asymmetric catalysis. Recently, organocatalysis, i.e. the use of small organic molecules to catalyze enantioselective transformations, has emerged as a prominent field in asymmetric synthesis. In this work, the use of hydrogels as a support for a chiral imidazolidinone organocatalyst (MacMillan catalyst) and its application in the reduction of activated olefins mediated by the Hantzsch ester is reported for the first time. Results showed a good activity of hydrogels in respect to both yield and enantioselection.
Sacchetti, Alessandro,Rossi, Filippo,Rossetti, Arianna,Pesa, Roberto,Mauri, Emanuele
p. 436 - 444
(2016/03/08)

Synthesis and evaluation of xanthine oxidase inhibitory and antioxidant activities of 2-arylbenzo[b]furan derivatives based on salvianolic acid C
Xanthine oxidase (XO) is the key enzyme in humans which is related to a variety of diseases such as gout, hyperuricemia and cardiovascular diseases. In this work, a series of 2-arylbenzo[b]furan derivatives were synthesized based on salvianolic acid C, and they were evaluated for xanthine oxidase inhibitory and antioxidant activities. Compounds 5b, 6a, 6e and 6f showed potent xanthine oxidase inhibitory activities with IC50values ranging from 3.99 to 6.36?μM, which were comparable with that of allopurinol. Lineweaver-Burk plots analysis revealed that the representative derivative 6e could bind to either xanthine oxidase or the xanthine oxidase-xanthine complex, which exhibited a mixed-type competitive mechanism. A DPPH radical scavenging assay showed most of the hydroxyl-functionalized 2-arylbenzo[b]furan derivatives possessed the potent antioxidant activity, which was further validated on LPS-stimulated RAW 264.7 macrophages model. The structure-activity relationships were preliminary analyzed and indicated that the structural skeleton of 2-arylbenzo[b]furan and phenolic hydroxyl groups played an important role in maintaining xanthine oxidase inhibitory effect and antioxidant property for the series of derivatives. Meanwhile, molecular docking studies were performed to further confirm the structure-activity relationships and investigate the proposed binding mechanisms of compounds 5d, 6d and 10d binding to the protein.
Tang, Hong-Jin,Zhang, Xiao-Wei,Yang, Lin,Li, Wei,Li, Jia-Huang,Wang, Jin-Xin,Chen, Jun
p. 637 - 648
(2016/09/14)

Synthesis of Met-enkephalin by solution-phase peptide synthesis methodology utilizing para-toluene sulfonic acid as N-terminal masking of l-methionine amino acid
The Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized by the solution-phase synthesis (SPS) methodology employing -OBzl group as carboxyls' protection, while the t-Boc groups were employed for the N-terminal α-amines' protection for the majority of the amino acids of the pentapeptide sequence. The l-methionine (l-Met) amino acid was used as PTSA.Met-OBzl obtained from the simultaneous protection of the α-amino, and carboxyl group with para-toluene sulfonic acid (PTSA) and as-OBzl ester, respectively in a C-terminal start of the 2?+?2?+?1 fragments condensation convergent synthetic approach. The protection strategy provided a short, single-step, simultaneous, orthogonal, nearly quantitative, robust, and stable process to carry through the protected l-methionine and l-phenylalanine coupling without any structural deformities during coupling and workups. The structurally confirmed final pentapeptide product was feasibly obtained in good yields through the current approach.
Khan, Riaz A.
p. 884 - 888
(2016/11/11)

Synthesis of MeO-PEG2000-supported chiral ferrocenyl oxazoline carbinol ligand and its application in asymmetric catalysis
A simple method for the synthesis of a MeO-PEG-supported chiral ferrocenyl oxazoline carbinol ligand has been developed. The chiral ligand was successfully applied to the catalytic asymmetric addition of diethylzinc to aryl aldehydes, affording secondary alcohols in high yields and with excellent enantioselectivities (up to 94% ee). The chiral ligand can be recovered and reused twice with no apparent loss of catalyst efficiency.
Zhao, Wen-Xian,Liu, Guan-Jun,Wang, Jingjing,Li, Feng,Liu, Lantao
p. 1133 - 1144
(2016/11/11)

A N-(9-fluorenylmethyloxycarbonyl)-O-tert-butyl-L-tyrosine method for the preparation of
The invention relates to a method for preparing N-(9-fluorenylmethoxy carbony)-O-tertiary butyl-L-tyrosine. The problem that an enantiomer is easily generated is solved. The method comprises the following synthetic steps: (1) dissolving L-Tyr into a methanol solution, adding SOCl2 and then carrying out reflux reaction, so as to obtain Tyr-OMe.HCl; (2) dissolving the Tyr-OMe.HCl into a water solution, adding AcOEt and Na2CO3 and then reacting with Z-Cl, and controlling the pH of the system at 7-10, so as to obtain Z-L-Tyr-OMe; (3) dissolving the Z-L-Tyr-OMe into a CH2Cl2 solution, adding H2SO4 and isobutene, reacting at normal temperature for 1-10 days, so as to obtain Z-L-Tyr(tBu)-OMe; (4) adding the NaOH solution to the Z-L-Tyr(tBu)-OMe to react, so as to obtain Z-L-Tyr(tBu); (5) dissolving the Z-L-Tyr(tBu) into methanol, adding Pd/C, and leading in hydrogen to react, so as to obtain L-Tyr(tBu); (6) dissolving Z-L-Tyr(tBu) into the water solution, adding the Na2CO3 and THF and then reacting with Fmoc-osu, and controlling the pH of the system at 8-10, so as to obtain Fmoc-Tyr(tBu). By adopting the method, generation of the enantiomer is avoided, and the citric acid is taken as an acidifier, so that the product is more stable, and the reaction processes do not relate to high-temperature and high-pressure reaction, and the method is applicable to large-scale production.
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Paragraph 0045; 0046

(2017/04/11)

A PRODUCING METHOD OF D-FORM OR L-FORM AMINO ACID DERIVATIVES HAVING A THIOL GROUP
This invention provides a producing method of an optical active D-form and/or L-form amino acid having a thiol group on its side chain by a simple method with good yield. This invention provides a producing method of an amino acid derivative having a thiol group on its side chain, and an intermediate thereof, wherein the producing method is characterized by producing an intermediate composition comprising a D-form and L-form of amino acid derivate having a thiol group at β -position, reacting D- or L-amino acid selective hydrolytic enzyme, and isolating the hydrolyzed D- or L-amino acid derivative.
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Paragraph 0164; 0165

(2016/10/31)