- Synthesis and biological evaluation of novel 1-Alkyl-tryptophan analogs as potential antitumor agents
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To seek novel antitumor agents, we designed and synthesized new 1-tryptophan analogs based on tryptophan catabolism. 1-Alkyl-tryptophan analogues including 1-ethyl-tryptophan (1-ET), 1-propyltryptophan (1-PT), 1-isopropyltryptophan (1-isoPT) and 1-butyltryptophan (1-BT) were synthesized from tryptophan. We examined whether those compounds had the antiproliferative effects on SGC7901 and HeLa cells line by using MTT assay in vitro, respectively. Compared to tryptophan, all targeted compounds efficiently inhibited proliferation of two cancer cell lines at 2 mmol/L for 48 hours. Among these tryptophan analogs, 1-BT showed the most powerful cytotoxicity against SGC7901 and HeLa cells at 1 mmol/L and 2 mmol/L concentration. These data suggest that some specific tryptophan analogs could be developed as potential anti-neoplastic agents.
- Sun, Ting,Li, Zhao-Long,Tian, Hua,Wang, Shih-Chen,Cai, Jiong
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- Supramolecular helix of an amphiphilic pyrene derivative induced by chiral tryptophan through electrostatic interactions
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An amphophilic pyrene derivative (PyDNH3) bearing positively charged ammonium cations has been synthesized and characterized. Self-assembly of PyDNH3 in the presence of chiral tryptophan derivatives was investigated in ethanol/water by optical and chiroptical spectra, indicating the formation of helical aggregates. Scanning electron microscope (SEM) images showed the formation of ring-shape structures.
- Xiao, Jinchong,Xu, Jialiang,Cui, Shuang,Liu, Huibiao,Wang, Shu,Li, Yuliang
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- Soluble non-cross-linked poly(norbornene) supports for peptide synthesis with minimal reagents
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Solid-phase peptide synthesis has been an attractive method for synthesizing peptides because it is quick and can be automated. The heterogeneous reaction medium in solid-phase peptide synthesis necessitates the use of large equivalents of reagents to drive the reactions to completion. Peptide synthesis using soluble, yet isolable, supports is an attractive alternative to solid-phase peptide synthesis. Reported herein is a soluble poly(norbornene)-derived support containing multiple attachment sites for high loading capacities and solubilizing oligoether/alkyl groups. The Ala-attached support has been used to synthesize tri- to octapeptides in 28 to 97% yields using only 1.2 equiv of amino acids and coupling reagents. The acyclic hexapeptide precursor to natural product segatalin A was synthesized in 41% yield on the support using one-eighth of the equivalents of coupling reagents compared to that in reported procedures. The support could be recovered in up to 98% yield after peptide synthesis, and the recovered support was utilized to synthesize tri- and tetrapeptides that contain amino acids other than Ala at the C-terminus in ca. 80% yields.
- Naganna, Nimmashetti,Madhavan, Nandita
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- Development of N-hydroxybenzamide derivatives with indole-containing cap group as histone deacetylases inhibitors
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Histone deacetylases inhibitors (HDACIs) have captured more and more attention in many diseases therapies, of which cancer is the most intractable. A novel series of N-hydroxybenzamide derivatives containing indole cap group was designed and synthesized. Most compounds exhibited excellent HDACs inhibitory activity, especially 8q-8v with low nanomolar IC50 values (1.5-13.0 nM), which were much more potent than the positive control SAHA. The most potent compound 8r showed slightly higher growth inhibitory activity than SAHA in multiple tumor cell lines, even though, antiproliferative activity of 8r seemed inferior to its HDAC inhibition activity. Poor transcellular permeability obtained from the result of HDAC class I cellular assay could explain the inferior antiproliferative activity. In addition, 8r displayed similar HDAC IIa cellular activity to class I, which indicated 8r might be a potent pan-HDAC inhibitor.
- Li, Xiaoyang,Wu, Jingde,Li, Xiaoguang,Mu, Weiwei,Liu, Xueliang,Jin, Yiming,Xu, Wenfang,Zhang, Yingjie
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- Lead discovery of a guanidinyl tryptophan derivative on amyloid cascade inhibition
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Amyloid cascade, one of pathogenic pathways of Alzheimer's disease (AD), was focused as one of drug discovery targets. In this study, β-secretase (BACE1) inhibitors were designed aiming at the development of multifunctional compounds targeting amyloid pathogenic cascade. Tryptophan was used as a core structure due to its properties of the central nervous system (CNS) penetration and BACE1 inhibition activity. Three amino acid residues and guanidine were selected as linkers to connect the tryptophan core structure and the extended aromatic moieties. The distance between the aromatic systems of the core structure and the extended moieties was kept at the optimal length for amyloid-β (Aβ) peptide binding to inhibit its fibrillation and aggregation. Sixteen designed compounds were evaluated in silico. Eight hit compounds of TSR and TGN series containing serine and guanidine linkers, respectively, were identified and synthesized based on docking results. TSR2 and TGN2 were found to exert strong actions as BACE1 (IC50 24.18 μM and 22.35 μM) and amyloid aggregation inhibitors (IC50 37.06 μM and 36.12 μM). Only TGN2 demonstrated a neuroprotective effect in SH-SY5Y cells by significantly reducing Aβ-induced cell death at a concentration of 2.62 μM. These results support the validity of multifunctional approaches to inhibition of the β-amyloid cascade.
- Jiaranaikulwanitch, Jutamas,Suwanttananuruk, Piyapan,Vajragupta, Opa,Waiwut, Pornthip
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- The (+/-)-1-(4-Methoxyphenyl)ethyl Ester as a Carboxyl Protecting Group
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Unhindered carboxylic acids were converted to their (+/-)-1-(4-methoxyphenyl)ethyl (MPe) esters in good yields by condensation with (+/-)-1-(4-methoxyphenyl)ethanol under mild conditions.The Mpe esters were rapidly and quantitatively cleavable by either 1percent TFA in CH2Cl2 or 10percent DCA in CH2Cl2, conditions which leave Boc, t-butyl ester and either intact.An Mpe ester was removed by hydrogenolysis much more slowsly than the analogous benzyl ester.
- Bernatowicz, Michael S.,Chao, Hann-Guang,Matsueda, Gary R.
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- Conditional changes enhanced production of bioactive metabolites of marine derived fungus Eurotium rubrum
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Metabolites of marine derived fungus Eurotium rubrum MPUC136 differed between cultivation on wheat medium and Czapek-Dox agar medium. Melanin synthesis inhibitory activity of crude extract of culture on wheat medium showed stronger activity than that of crude extract of culture on Czapek-Dox agar medium. A new diketopiperazine compound isoechinulin D (1) and eight reported diketopiperazines (2–9) were isolated from the crude extract of wheat medium. The structure of 1 was established using NMR, MS and IR methods. 2–5 inhibited melanogenesis using B16 melanoma cells (IC50?=?68, 2.4, 83, 9.1?μM each). Structure–Activity-Relationships of diketopiperazines (1–10) indicated the importance of the prenyl groups at C-2, C-5 and C-7, the vinyl group at C-12 to C-25 and the sp2carbons at C-8 and C-9. Isolated compounds (1–9) were not or slightly observed from the extracts of Czapek-Dox agar medium by HPLC analysis, suggesting that different cultivation processes could affect metabolism and enhance bioactivities.
- Kamauchi, Hitoshi,Kinoshita, Kaoru,Sugita, Takashi,Koyama, Kiyotaka
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- Pseudo-peptides as novel antileptospiral agents: Synthesis and spectral characterization
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In this paper, we describe the synthesis of novel class of pseudo-peptides derived by coupling an amino acid with a heterocyclic moiety containing free amine group using suitable coupling agents. The synthesized compounds were characterized using spectral (1H NMR, 13C NMR and MS) techniques. Preliminary pharmacological assays for Leptospirosis were studied by test tube dilution (TDT) and micro dilution technique (MDT). In particular, all the analyses led to the conclusion that the synthesized compound inhibiting the Leptospira a causal organism of Leptospirosis.
- Shivamallu, Chandan,Sharanaiah, Umesha,Kollur, Shiva Prasad,Mallesh, Naveen Kumar R.,Hosakere, Revanasiddappa D.,Balamurugan
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- L-Proline induced self-assembly of indolicidin derived palindromic tripeptide
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We describe the synthesis, crystal structure, and various microscopic studies of the palindromic tripeptide WPW derived from antimicrobial peptide indolicidin. The present study reveals that tripeptide 1 and 2 undergo self-assembly to form vesicular structures after prolonged incubation, thus giving an interesting insight into the contribution of l-proline and flanking tryptophan residues in the self-assembly process. These vesicles were also amenable to simple focused ion beam (FIB)-aided bisection and thus possible to mill these vesicles to create different shapes. The circular dichroism (CD) analysis indicates that incubation promotes and stabilizes the more favorable secondary structures for 1 and 2. Preliminary result shows that tripeptide 1 exhibits appreciable interaction with Tb3+ as determined by quenching in tryptophan fluorescence.
- Joshi, Khashti Ballabh,Singh, Prabhpreet
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- Enantioselective recognition by optically active chiral fluorescence sensors bearing amino acid units
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Chiral fluorescence receptors 1 and 2 were synthesized and their structures characterized by IR, 1H NMR, 13C NMR, MS spectra, and elemental analysis. The chiral recognition abilities of 1 and 2 were studied by 1H NMR and fluorescence spectra. The results demonstrate that receptors 1 and 2 with bis(tetrabutylammonium) dibenzoyl tartrate formed a 1:1 complex. Receptor 2 exhibits an excellent enantioselective recognition ability toward the enantiomers of bis(tetrabutylammonium) dibenzoyl tartrate.
- Xu, Kuo-Xi,He, Yong-Bing,Qin, Hai-Juan,Qing, Guang-Yan,Liu, Shun-Ying
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- Amino acid derivatives, IX [1]: Synthesis and antimicrobial evaluation of α-amino acid esters bearing a tryptophane side chain
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A series of peptide and dipeptide derivatives conjugated with a tryptophane residue were synthesized. The prepared compounds were tested for antimicrobial activity against four different bacterial species displaying different degrees of antibacterial activities or inhibitory actions.
- Hameurlaine, Ahmed,El-Sayed, Wael A.,Abdel-Rahman, Adel A.-H.
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- Design, synthesis, and biological evaluation of non-peptidic ligands at the Xenopus laevis skin-melanocortin receptor
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Taking the tripeptide D-Trp-Arg-Leu-NH2 as a lead for a Xenopus laevis skin-melanocortin (MC) receptor antagonist, thirteen non-peptidic compounds were synthesized and biologically evaluated at Xenopus laevis melanophores. Six competitive antagonists (shown by Schild analysis) and one partial agonist were identified with moderate activity (IC50: 5-10 μM). Tryptophanamides with aliphatic side chains were inactive whereas basic residues restored activity. Introducing an imidazole residue yielded partial agonist activity (EC50: 32 μM). Interestingly, constraining the inactive S-tryptophan-isoamylamide to a β-carboline ring yielded an MC receptor antagonist (42). The specificity for MC receptors was tested at various G-protein coupled receptors. In conclusion, the synthesis of non-peptidic MC receptor antagonists is described which may serve as lead compounds for further studies.
- Tammler, Ursula,Quillan, J. Mark,Lehmann, Jochen,Sadee, Wolfgang,Kassack, Matthias U.
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- Design and synthesis of enantiopure 18F-labelled [18F]trifluoromethyltryptophan from 2-halotryptophan derivatives via copper(I)-mediated [18F]trifluoromethylation and evaluation of its in vitro characterization for the serotonergic system imaging
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We synthesized [18F]trifluoromethyl-l-tryptophan ([18F]CF3-l-Trp) using Cu(I)-mediated [18F]trifluoromethylation to image serotonergic system. Radiochemical yield was 6 ± 1.5% (n = 9), and radiochemical purity was over 99%. The molar activity was 0.44 to 0.76 GBq/μmol. [18F]CF3-l-Trp was stable for up to 6 hours in mouse and human sera at 37°C. Protein-binding was 0.26 ± 0.03% and 0.34 ± 0.02% in human and mouse serum at 60 minutes, respectively. In conclusion, enantiopure [18F]CF3-l-Trp was synthesized as a feasible imaging agent for the serotonergic system.
- Kim, Ho Young,Lee, Ji Youn,Lee, Yun-Sang,Jeong, Jae Min
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- Does water suppress the racemization and decomposition of amino acids?
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Several neutral free amino acids, phenylglycine, leucine, phenylalanine and tryptophan, are heated at 100-130 °C under alkaline or acidic conditions in water or various polar organic solvents. Although serious racemization and decomposition occur in polar organic solvents such as DMF, DMSO, or ethylene glycol under alkaline conditions (K2CO3, KOH, Et3N), these phenomena do not occur, or are largely decreased, in water or water-containing organic solvents under the same alkaline conditions. Serious racemization and decomposition of free phenylglycine are also observed in AcOH, while water or aqueous AcOH (90%) largely suppress the racemization and decomposition. We discuss the possible reasons for this suppression effect of water in terms of differential solvation of bases and states of dissociation of amino acids in aqueous and organic solvents.
- Yokoyama,Hikawa,Murakami
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- Translation of Mycobacterium Survival Strategy to Develop a Lipo-peptide based Fusion Inhibitor**
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The entry of enveloped virus requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad-spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome–lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40-repeat protein suggest that the trp-asp (WD) sequence is placed at distorted β-meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo-peptide sequence (myr-WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo-dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a potential broad-spectrum antiviral agent.
- Sardar, Avijit,Lahiri, Aritraa,Kamble, Mithila,Mallick, Amirul I.,Tarafdar, Pradip K.
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supporting information
p. 6101 - 6106
(2021/02/01)
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- Convenient Synthesis of Alternatively Bridged Tryptophan Ketopiperazines and Their Activities against Trypanosomatid Parasites
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There is an urgent need for the development of new treatments against trypanosomatid parasites; the causative agents of some of the most debilitating diseases in the developing world. This work targets an interesting 6-5-6-6 fused carboline scaffold, accessing a range of substituted derivatives through stereospecific intramolecular Pictet–Spengler condensation. Modification of the cyclisation conditions allowed retention of the carbamate protecting group and gave insight into the reaction mechanism. Compounds’ bioactivities were measured against T. brucei, T. cruzi, L. major and HeLa cells. We have identified promising pan-trypanocidal lead compounds based on the core scaffold, and highlight key SAR trends which will be useful for the future development of these compounds as potent trypanocidal agents.
- Cockram, Peter E.,Slawin, Alexandra M. Z.,Smith, Terry K.,Turner, Callum A.
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supporting information
(2022/01/11)
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- SMALL-MOLECULAR ADJUVANTS AND IMPLEMENTATIONS THEREOF
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The present disclosure describes compounds of the general Formula (I) or its stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates, hydrates, thereof. These compounds or small molecular adjuvants in combination with antibiotics are effective against resistant bacterial infections. The present disclosure also discloses a process of preparation of small-molecular adjuvants, its stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates and hydrates thereof, and to pharmaceutical compositions containing them
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Paragraph 0090; 0092; 00117
(2020/10/27)
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- Cu-Catalyzed Site-Selective C(sp2)-H Radical Trifluoromethylation of Tryptophan-Containing Peptides
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Site-selective functionalization of C-H bonds within a peptide framework poses a challenging task of paramount synthetic relevance. Herein, we report an operationally simple C(sp2)-H trifluoromethylation of tryptophan (Trp)-containing peptides. This fluorination technique is characterized by its chirality preservation, tolerance of functional groups, and scalability and exhibits chemoselectivity for Trp residues over other amino acid and heterocyclic units. As a result, it represents a sustainable tool toward the late-stage peptide modification and protein engineering.
- Correa, Arkaitz,Guerrero, Itziar
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supporting information
p. 1754 - 1759
(2020/03/23)
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- Mild deprotection of the: N-tert -butyloxycarbonyl (N -Boc) group using oxalyl chloride
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We report a mild method for the selective deprotection of the N-Boc group from a structurally diverse set of compounds, encompassing aliphatic, aromatic, and heterocyclic substrates by using oxalyl chloride in methanol. The reactions take place under room temperature conditions for 1-4 h with yields up to 90percent. This mild procedure was applied to a hybrid, medicinally active compound FC1, which is a novel dual inhibitor of IDO1 and DNA Pol gamma. A broader mechanism involving the electrophilic character of oxalyl chloride is postulated for this deprotection strategy. This journal is
- Awuah, Samuel G.,George, Nathaniel,Ofori, Samuel,Parkin, Sean
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p. 24017 - 24026
(2020/07/23)
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- A class of DL-tryptophan compounds, preparation method and applications thereof
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The invention provides a DL-tryptophan compound represented by a general formula I or a pharmaceutically acceptable salt thereof, a preparation method and applications thereof, especially applicationsin preparation of RANKL inhibitors. According to the DL-tryptophan compound or the pharmaceutically acceptable salt thereof, an OPG-RANKL-RANK signal system can be intervened by inhibiting the interaction of RANKL-RANK, and the activity of RANKL in osteoclast precursor cells is regulated and controlled, so that formation of osteoclasts is inhibited, and bone resorption is reduced; and the DL-tryptophan compound or the pharmaceutically acceptable salt thereof is expected to play a role in preventing and treating bone metabolic diseases, and brings good news to bone metabolic disease patients.
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Paragraph 0058-0061
(2020/06/17)
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- A Facile Approach to the Synthesis of Benzothiazoles from N-Protected Amino Acids
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Abstract: –A simple trituration method for the synthesis of 2-substituted benzothiazoles derived from N-protected amino acids and 2-aminothiophenol using molecular iodine as a mild Lewis acid catalyst has been proposed. The reaction occurs in one step for 20–25 min in solve-free conditions and provides the target products in excellent yields.
- Arfan, M.,Fatima, T.,Mannan, A.,Tahira, A.
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p. 292 - 297
(2020/04/21)
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- Compounding of (N-alkyl benzpyrole)-diketopiperazine compound and application of compound as plant growth regulator
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The invention relates to compounding of a (N-alkyl benzpyrole)-diketopiperazine compound and application of the compound as a plant growth regulator. The chemical structural formula of the compound isshown as the general formula (I) and the general formula (II), wherein * in the general formula (I) and the general formula (II) represents chiral center, and spatial configuration is R or S; and R1and R2 represent substituent groups. For more details, please see the instruction.
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Paragraph 0031-0035
(2019/12/25)
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- Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease
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A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit Aβ42 self-aggregation (58.6 ± 5.1% at 50 μM) as well as hAChE-induced Aβ40 aggregation (48.3 ± 6.3% at 100 μM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia.
- Chalupova, Katarina,Korabecny, Jan,Bartolini, Manuela,Monti, Barbara,Lamba, Doriano,Caliandro, Rosanna,Pesaresi, Alessandro,Brazzolotto, Xavier,Gastellier, Anne-Julie,Nachon, Florian,Pejchal, Jaroslav,Jarosova, Michaela,Hepnarova, Vendula,Jun, Daniel,Hrabinova, Martina,Dolezal, Rafael,Zdarova Karasova, Jana,Mzik, Martin,Kristofikova, Zdena,Misik, Jan,Muckova, Lubica,Jost, Petr,Soukup, Ondrej,Benkova, Marketa,Setnicka, Vladimir,Habartova, Lucie,Chvojkova, Marketa,Kleteckova, Lenka,Vales, Karel,Mezeiova, Eva,Uliassi, Elisa,Valis, Martin,Nepovimova, Eugenie,Bolognesi, Maria Laura,Kuca, Kamil
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p. 491 - 514
(2019/03/08)
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- Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans
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Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 μg/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.
- Jovanovic, Milos,Radivojevic, Jelena,O'Connor, Kevin,Blagojevic, Stevan,Begovic, Biljana,Lukic, Vera,Nikodinovic-Runic, Jasmina,Savic, Vladimir
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supporting information
p. 209 - 217
(2019/03/23)
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- A new type of L-Tertiary leucine-derived ligand: Synthesis and application in Cu(II)-catalyzed asymmetric Henry reactions
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A new series of Schiff bases derived from amino acids were developed as chiral ligands for Cu(II)-catalyzed asymmetric Henry reactions. The optimum ligand 7d exhibited outstanding catalytic efficiency in the Cu(II)-catalyzed asymmetric Henry additions of four nitroalkanes to different kinds of aldehydes to produce 76 desired adducts in high yields (up to 96%) with excellent enantioselectivities, up to 99% enantiomeric excess (ee).
- Cai, Zedong,Lan, Ting,Ma, Pengfei,Zhang, Jingfang,Yang, Qingqing,He, Wei
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- Development of Small-Molecules Targeting Receptor Activator of Nuclear Factor-κB Ligand (RANKL) - Receptor Activator of Nuclear Factor-κB (RANK) Protein-Protein Interaction by Structure-Based Virtual Screening and Hit Optimization
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Targeting RANKL/RANK offers the possibility of developing novel therapeutic approaches to treat bone metabolic diseases. Multiple efforts have been made to inhibit RANKL. For example, marketed monoclonal antibody drug Denosumab could inhibit the maturation of osteoclasts by binding to RANKL. This study is an original approach aimed at discovering small-molecule inhibitors impeding RANKL/RANK protein interaction. We identified compound 34 as a potent and selective RANKL/RANK inhibitor by performing structure-based virtual screening and hit optimization. Disruption of the RANKL/RANK interaction by 34 effectively inhibits RANKL-induced osteoclastogenesis and bone resorption. The expression of osteoclast marker genes was also suppressed by treatment of 34. Furthermore, 34 markedly blocked the NFATc1/c-fos pathway. Thus, our current work demonstrates that the chemical tractability of the difficult PPI (RANKL/RANK) target by a small-molecule compound 34 offers a potential lead compound to facilitate the development of new medications for bone-related diseases.
- Jiang, Min,Peng, Lei,Yang, Kai,Wang, Tianqi,Yan, Xueming,Jiang, Tao,Xu, Jianrong,Qi, Jin,Zhou, Hanbing,Qian, Niandong,Zhou, Qi,Chen, Bo,Xu, Xing,Deng, Lianfu,Yang, Chunhao
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supporting information
p. 5370 - 5381
(2019/06/24)
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- CONTINUOUS, SOLVENT-FREE AND NON-ENZYMATIC PEPTIDE SYNTHESIS BY REACTIVE EXTRUSION
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The present disclosure relates to A a continuous, solvent-free and non-enzymatic method for synthesizing a compound of formula (I): Ra-POLYPEP-Rc (I) wherein: POLYPEP is a poly-amino acid compound, Ra and Rc are as specified in the disclosure, which method comprises the steps of: a) feeding an extrusion reactor with (1) a compound of formula (II) Ra-PEPNt-Rg (II) wherein; PEPNt is a mono- or a poly-aminoacid compound, Ra and Rg are as specified in the disclosure, and (2) a compound of formula (III) H-PEPCt-Rc (III) wherein: PEPCt is a mono- or a poly-amino acid compound, and Rc is as defined in the disclosure in the absence of any solvent, so that the compound of formula (II) and the compound of formula (III) react together for generating a compound of formula (I), and b) collecting the compound of formula (I) from the extrusion reactor.
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Page/Page column 32; 33
(2019/09/04)
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- Synthesis of Main-Chain Ionic Polymers of Chiral Imidazolidinone Organocatalysts and Their Application to Asymmetric Diels–Alder Reactions
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Main-chain ionic polymers incorporating chiral imidazolidinone moieties in the polymer main chain were successfully synthesized by the polyaddition reaction of a chiral imidazolidinone dimer with a disulfonic acid. The organocatalytic activities of these polymers were investigated in the asymmetric Diels–Alder reaction between trans-cinnamaldehyde and 1,3-cyclopentadiene. The catalytic performance of the polymers was found to be sensitive to the chemical structure of the disulfonate units and the imidazolidinone dimer. With the use of these heterogeneous polymeric chiral organocatalysts, enantioselectivities of up to 99% for the endo isomer were obtained. This result was higher than those obtained with corresponding monomeric and dimeric counterparts in a homogeneous solution. The polymeric chiral organocatalyst was recovered and reused several times, maintaining its high enantioselectivity. (Figure presented.).
- Haraguchi, Naoki,Takenaka, Nagisa,Najwa, Aisyah,Takahara, Yuta,Mun, Mah Kar,Itsuno, Shinichi
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supporting information
p. 112 - 123
(2017/12/26)
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- N-methyl-D-aspartate receptor modulators and methods of making and using same
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Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
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Page/Page column 47; 48; 49
(2018/06/25)
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- Amino acid conjugated antimicrobial drugs: Synthesis, lipophilicity- activity relationship, antibacterial and urease inhibition activity
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Present work describes the in vitro antibacterial evaluation of some new amino acid conjugated antimicrobial drugs. Structural modification was attempted on the three existing antimicrobial pharmaceuticals namely trimethoprim, metronidazole, isoniazid. Twenty one compounds from seven series of conjugates of these drugs were synthesized by coupling with some selected Boc-protected amino acids. The effect of structural features and lipophilicity on the antibacterial activity was investigated. The synthesized compounds were evaluated against five standard American type culture collection (ATCC) i.e. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi strains of bacteria. Our results identified a close relationship between the lipophilicity and the activity. Triazine skeleton proved beneficial for the increase in hydrophobicity and potency. Compounds with greater hydrophobicity have shown excellent activities against Gram-negative strains of bacteria than Gram-positive. 4-amino unsubstituted trimethoprim-triazine derivative 7b have shown superior activity with MIC = 3.4 μM (2 μg/mL) for S. aureus and 1.1 μM (0.66 μg/mL) for E. coli. The synthesized compounds were also evaluated for their urease inhibition study. Microbial urease from Bacillus pasteurii was chosen for this study. Triazine derivative 7a showed excellent inhibition with IC50 = 6.23 ± 0.09 μM. Docking studies on the crystal structure of B. pasteurii urease (PDB ID 4UBP) were carried out.
- Ullah, Atta,Iftikhar, Fatima,Arfan, Muhammad,Batool Kazmi, Syeda Tayyaba,Anjum, Muhammad Naveed,Haq, Ihsan-ul,Ayaz, Muhammad,Farooq, Sadia,Rashid, Umer
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p. 140 - 153
(2018/01/10)
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- Synthesis and evaluation of chirally defined side chain variants of 7-chloro-4-aminoquinoline to overcome drug resistance in malaria chemotherapy
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A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methyl-piperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.
- Dola, Vasantha Rao,Soni, Awakash,Agarwal, Pooja,Ahmad, Hafsa,Raju, Kanumuri Siva Rama,Rashid, Mamunur,Wahajuddin, Muhammad,Srivastava, Kumkum,Haq,Dwivedi,Puri,Katti
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- Design, synthesis, and preliminary bioactivity evaluation of N1-hydroxyterephthalamide derivatives with indole cap as novel histone deacetylase inhibitors
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Histone deacetylases inhibitors (HDACIs) have been widely recognized as significant therapeutic approach to cancers. In our efforts to develop novel histone deacetylases inhibitors (HDACIs) as potential anticancer agents, a series of N1-hydroxyterephthalamide derivatives with an indole cap group were designed and synthesized. Compound 12m was identified to be the most potent one (IC50?=?0.074?μm against HeLa nuclear extract) and showed higher inhibitory activity than the positive control SAHA (IC50?=?0.131?μm), which was also verified by further molecular docking studies into active site of HDAC2. The results of selectivity on the inhibition of HDACs exhibited 12m being with similar isoform selective profile with PXD101. In addition, the representative compounds (8d, 12d, 12j, 12m) based on the outcomes of preliminary tumor cell screening demonstrated more potent or comparable to SAHA in the next antiproliferative activity assays. Collectively, the results encouraged further development of this chemical template to provide more potent analogs as HDACIs.
- Wang, Xue,Li, Xiaoyang,Li, Jingyao,Hou, Jinning,Qu, Ying,Yu, Chenggong,He, Feng,Xu, Wenfang,Wu, Jingde
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- Dynamic self-assembled polymer: HCl responsive inversion of supramolecular polymer handedness
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A series of discotic tricarboxyamides with varied amino acid side arm functionality and their HCl responsive diverse self-assembly behavior and formation of dynamic polymer is studied. Discotic trisamide 1 obtained from Boc protected l-Lys self-assembled into a long fibrillar aggregate-like supramolecular P helical polymer. However, on addition of HCl, the supramolecular helical handedness of the assemblies is completely inverted. Irrespective of the chiral centres configuration, supramolecular chiral bias is arising from molecular conformations. FE-SEM reveals the formation of right handed entangled polymeric fibers. However, left handed entangled fibers have appeared on addition of 0.12 M HCl. The trisamide 2 containing Boc protected l-Trp exhibits disk like morphology both in the presence and absence of 0.12 M HCl and does not show a change of supramolecular handedness. This demonstrates how remarkably distinct morphologies originate from stimuli responsive building blocks assembled in a subtly different manner.
- Paikar, Arpita,Haldar, Debasish
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p. 47170 - 47176
(2017/10/13)
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- Non-peptide tachykinin receptor antagonist preparation method
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The invention discloses a non-peptide tachykinin receptor antagonist preparation method. A synthetic route of a non-peptide tachykinin receptor antagonist is as shown in the specification. The non-peptide tachykinin receptor antagonist preparation method has advantages of simplicity and feasibility in operation, cheap and easy in acquisition of raw materials, high reaction efficiency and high repeatability.
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Paragraph 0029; 0030; 0031; 0032
(2017/08/29)
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- The method of synthesis for preparing compound
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A synthesis method of a compound shown as a formula I is provided. The method includes (1) bringing a compound shown as a formula 1 into contact with BOC anhydride to produce a compound shown as a formula 2; (2) bringing the compound shown as the formula 2 into contact with a compound shown as a formula 3 to produce a compound shown as a formula 4; (3) subjecting the compound shown as the formula 4 to amino deprotection to produce a compound shown as a formula 5; and (4) bringing the compound shown as the formula 5 into contact with a compound shown as a formula 6 to produce the compound shown as the formula I that is Tadalafil. The method prepares the Tadalafil through four steps of reactions. The total yield reaches 36.1%. Process steps of the method are simple. Initial raw materials are cheap and easily available. All the intermediates are easy to purify. After-treatment operation is simple. The content of impurities in a finished product is low. The target product is high in purity. Compared with other Tadalafil preparing processes at present, the method obviously reduces environment pollution and benefits industrial production.
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Paragraph 0054-0056
(2017/09/01)
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- New reagent for the introduction of Boc protecting group to amines: Boc-OASUD
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A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.
- Maheswara Rao, B. Leela,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
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supporting information
p. 2127 - 2132
(2017/10/31)
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- Desyl and phenacyl as versatile, photocatalytically cleavable protecting groups: A classic approach in a different (visible) light
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A highly efficient, catalytic strategy for the deprotection of classical phenacyl (Pac) as well as desyl (Dsy) protection groups has been developed using visible light photoredox catalysis. The deliberate use of a neutral two-phase acetonitrile/water mixture with K3PO4 applying catalytic amounts of [Ru(bpy)3](PF6)2 in combination with ascorbic acid is the key to this truly catalytic deprotection of Pac- and Dsy-protected carboxylic acids. Our mild yet robust protocol allows for fast and selective liberation of the free carboxylic acids in very good to quantitative yields, while only low catalyst loadings (1 mol %) are required. Both Pac and Dsy, easily introduced from commercially available precursors, can be applied for the direct protection of carboxylic acids and amino acids, offering orthogonality to a great variety of other common protecting groups. We further demonstrate the general applicability and versatility of these formerly underrated protecting groups in combination with our catalytic cleavage conditions, as underscored by the gained high functional group tolerance. Moreover, this method could successfully be adapted to the requirements of solidphase synthesis. As a proof of principle for an efficient visible light, photocatalytic linker cleavage, a Boc-protected tripeptide was split off from commercially available brominated Wang resin.
- Speckmeier, Elisabeth,Zeitler, Kirsten
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p. 6821 - 6826
(2017/11/06)
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- C ring may be dispensable for β-carboline: Design, synthesis, and bioactivities evaluation of tryptophan analog derivatives based on the biosynthesis of β-carboline alkaloids
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According to our previous work and the latest research on the biosynthesis of β-carboline, and using the reverse thinking strategy, tryptophan, the biosynthesis precursor of β-carboline alkaloids, and their derivatives were synthesized, and their biological activities and structure-activity relationships were studied. This bioassay showed that these compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV); especially (S)-2-amino-3-(1H-indol-3-yl)-N-octylpropanamide (4) (63.3 ± 2.1%, 67.1 ± 1.9%, 68.7 ± 1.3%, and 64.5 ± 3.1%, 500 μg/mL) exhibited the best antiviral activity both in vitro and in vivo. Compound 4 was chosen for the field trials and the acute oral toxicity test, the results showed that the compound exhibited good anti-TMV activity in the field and low acute oral toxicity. We also found that these compounds showed antifungal activities and insecticidal activities.
- Huang, Yuanqiong,Liu, Yongxian,Liu, Yuxiu,Song, Hongjian,Wang, Qingmin
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p. 462 - 473
(2016/01/25)
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- Tryptophan derivative, preparing method and application in preventing and treating plant viruses, killing bacteria and killing insects
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The invention relates to a tryptophan derivative (I), a preparing method of the tryptophan derivative (I), and application of the tryptophan derivative (I) in preventing and treating plant viruses, killing bacteria and killing insects. The formula of the tryptophan derivative (I) is shown in the description, and the meanings of all groups in the formula are shown in the description. The tryptophan derivative expresses especially excellent plant virus resisting activity, and also has broad-spectrum bactericidal activity and insecticidal activity.
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Paragraph 0095; 0096; 0097
(2017/06/02)
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- Substituted pyrimidine derivatives with Akt inhibiting activity, and preparation method and application thereof
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The invention relates to novel substituted pyrimidine derivatives with Akt inhibiting activity and a preparation method thereof, a pharmaceutical composition comprising the substituted pyrimidine derivatives and salts thereof, and application of the substituted pyrimidine derivatives and salts thereof in preparing drugs for preventing and/or treating tumors. The structural formula of the compounds is disclosed as Formula (I) or Formula (II). The compounds have the advantages of novel structure, outstanding Akt inhibiting activity, high safety and low preparation cost, and have favorable application prospects in preparing antineoplastic drugs.
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Paragraph 0149; 0150; 0153
(2016/12/16)
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- Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors
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The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors′ binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121–ligand recognition and speculation into the biological role of the enzyme for Mtb.
- Kavanagh, Madeline E.,Gray, Janine L.,Gilbert, Sophie H.,Coyne, Anthony G.,McLean, Kirsty J.,Davis, Holly J.,Munro, Andrew W.,Abell, Chris
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supporting information
p. 1924 - 1935
(2016/10/06)
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- Dehydrodipeptide Hydrogelators Containing Naproxen N-Capped Tryptophan: Self-Assembly, Hydrogel Characterization, and Evaluation as Potential Drug Nanocarriers
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In this work, we introduce dipeptides containing tryptophan N-capped with the nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids, dehydrophenylalanine (ΔPhe), dehydroaminobutyric acid (ΔAbu), and dehydroalanine (ΔAla) as efficacious protease resistant hydrogelators. Optimized conditions for gel formation are reported. Transmission electron microscopy experiments revealed that the hydrogels consist of networks of micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular dichroism spectroscopy indicate that the self-assembly process is driven by stacking interactions of the aromatic groups. The naphthalene groups of the naproxen moieties are highly organized in the fibers through chiral stacking. Rheological experiments demonstrated that the most hydrophobic peptide (containing C-terminal ΔPhe) formed more elastic gels at lower critical gelation concentrations. This gel revealed irreversible breakup, while the C-terminal ΔAbu and ΔAla gels, although less elastic, exhibited structural recovery and partial healing of the elastic properties. A potential antitumor thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel formed by the hydrogelator containing C-terminal ΔPhe residue. Fluorescence and F?rster resonance energy transfer measurements indicate that the drug is located in a hydrophobic environment, near/associated with the peptide fibers, establishing this type of hydrogel as a good drug-nanocarrier candidate.
- Vila?a, Helena,Hortel?o, Ana C. L.,Castanheira, Elisabete M. S.,Queiroz, Maria-Jo?o R. P.,Hilliou, Loic,Hamley, Ian W.,Martins, José A.,Ferreira, Paula M. T.
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p. 3562 - 3573
(2015/11/17)
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- Dual Catalytic Decarboxylative Allylations of α-Amino Acids and Their Divergent Mechanisms
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The room temperature radical decarboxylative allylation of N-protected α-amino acids and esters has been accomplished via a combination of palladium and photoredox catalysis to provide homoallylic amines. Mechanistic investigations revealed that the stability of the α-amino radical, which is formed by decarboxylation, dictates the predominant reaction pathway between competing mechanisms.
- Lang, Simon B.,O'Nele, Kathryn M.,Douglas, Justin T.,Tunge, Jon A.
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supporting information
p. 18589 - 18593
(2016/01/25)
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- Synthesis of tryptophans by alkylation of chiral glycine enolate equivalents with quaternary gramines
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Quaternary gramines were found to be a suitable source of the 3-methylindole fragment for diastereoselective alkylation. The best yields and stereoselectivity were obtained for the alkylation of a chiral William's morpholinone enolate. Based on this transformation, a general method for the synthesis of enantiopure, indole ring substituted tryptophan derivatives was developed with good overall yields.
- Reinfelds, Matiss,Kalinins, Konstantins,Katkevica, Dace,Zemribo, Ronalds,Katkevics, Martins
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p. 5882 - 5885
(2015/11/02)
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- Antiplasmodial activity of new 4-aminoquinoline derivatives against chloroquine resistant strain
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Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum. The key feature of the designed molecules is the use of methylpiperazine linked α, β3- and γ-amino acids to generate novel side chain modified 4-aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI = 5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target.
- Sinha, Manish,Dola, Vasanth R.,Agarwal, Pooja,Srivastava, Kumkum,Haq, Wahajul,Puri, Sunil K.,Katti, Seturam B.
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p. 3573 - 3586
(2014/07/07)
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- Design, synthesis and evaluation of novel tacrine-(β-carboline) hybrids as multifunctional agents for the treatment of Alzheimer's disease
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A series of tacrine-(β-carboline) hybrids (11a-q) were designed, synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (BuChE) and self-induced β-amyloid (Aβ) aggregation, Cu2+-induced Aβ (1-42) aggregation, and to chelate metal ions. Especially, 11l presented the greatest ability to inhibit cholinesterase (IC50, 21.6 nM for eeAChE, 63.2 nM for hAChE and 39.8 nM for BuChE), good inhibition of Aβ aggregation (65.8% at 20 μM) and good antioxidant activity (1.57 trolox equivalents). Kinetic and molecular modeling studies indicated that 11l was a mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 11l could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). These results suggested that 11l might be an excellent multifunctional agent for AD treatment.
- Lan, Jin-Shuai,Xie, Sai-Sai,Li, Su-Yi,Pan, Long-Fei,Wang, Xiao-Bing,Kong, Ling-Yi
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p. 6089 - 6104
(2015/02/02)
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- Encapsulation of a catalytic imidazolium salt into avidin: Towards the development of a biohybrid catalyst active in ionic liquids
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Herein, we report the development of biohybrid catalysts that are capable of catalyzing the aldol reaction. The use of biotinylated imidazolium salts in combination with racemic or enantiomerically pure catalytic anions allowed us to study the adaptive and cooperative positioning of the anionic catalyst inside the protein. Supramolecular encapsulation of the biotinylated catalyst into avidin resulted in good selectivity for the aldol reaction performed in ionic liquid/water mixtures. Biohybrid catalysts capable of catalyzing the aldol reaction are prepared from avidin and biotinylated imidazolium salts with either racemic or enantiomerically pure catalytic anions. Supramolecular encapsulation (see figure) of the biotinylated catalyst in avidin resulted in good selectivities for the aldol reaction when performed in ionic liquid/water mixtures and the adaptive and cooperative positioning of the anionic catalyst inside the avidin protein is discussed. Copyright
- Gauchot, Vincent,Branca, Mathieu,Schmitzer, Andreea
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supporting information
p. 1530 - 1538
(2014/03/21)
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- DI-AND TRI-HETEROARYL DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION
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The present invention relates to certain di- and tri-heteroaryl derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, and multiple system atrophy.
- -
-
Paragraph 0125; 0128
(2014/02/15)
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- Synthesis of l -octaarginine through microencapsulated palladium-catalyzed allyl ester deprotection
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Octaarginine has been described as a molecular transporter. We report a useful synthesis of orthogonally protected l-octaarginine by using a method based on a microencapsulated palladium catalyst. Known palladium-based methods for allyl ester deprotection have been modified to facilitate purification of the unprotected intermediates. This improvement in the purification step has also been tested with a variety of allyl α-amino esters and allyl α,β-unsaturated esters.
- Pérez-López, Ana M.,González-Calderón, Dávir,Occorso, Antonio,Galindo-ángel, Javier,Domínguez-Seglar, José F.,Tamayo, Juan A.,Díaz-Gavilán, Mónica,Gómez-Vidal, José A.
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supporting information
p. 2319 - 2322
(2015/08/06)
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- From BACE1 Inhibitor to Multifunctionality of tryptoline and tryptamine triazole derivatives for alzheimer's disease
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Efforts to discover new drugs for Alzheimer's disease emphasizing multiple targets was conducted seeking to inhibit amyloid oligomer formation and to prevent radical formation. The tryptoline and tryptamine cores of BACE1 inhibitors previously identified by virtual screening were modified in silico for additional modes of action. These core structures were readily linked to different side chains using 1,2,3-triazole rings as bridges by copper catalyzed azide-alkyne cycloaddition reactions. Three compounds among the sixteen designed compounds exerted multifunctional activities including β-secretase inhibitory action, anti-amyloid aggregation, metal chelating and antioxidant effects at micromolar levels. The neuroprotective effects of the multifunctional compounds 6h, 12c and 12h on Aβ1-42 induced neuronal cell death at 1 ?M were significantly greater than those of the potent single target compound, BACE1 inhibitor IV and were comparable to curcumin. The observed synergistic effect resulting from the reduction of the Aβ1-42 neurotoxicity cascade substantiates the validity of our multifunctional strategy in drug discovery for Alzheimer's disease.
- Jiaranaikulwanitch, Jutamas,Govitrapong, Piyarat,Fokin, Valery V.,Vajragupta, Opa
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experimental part
p. 8312 - 8333
(2012/10/18)
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- Perylen-3-ylmethyl: Fluorescent photoremovable protecting group (FPRPG) for carboxylic acids and alcohols
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Perylen-3-ylmethyl demonstrated as a new fluorescent photoremovable protecting group (FPRPG) for carboxylic acids and alcohols. Carboxylic acids including amino acids were protected as their corresponding esters by coupling with FPRPG, perylen-3-ylmethyl. Photophysical studies of caged esters showed that they all exhibited strong fluorescence properties and their fluorescence quantum yields were in the range of 0.85-0.95. Irradiation of the caged esters using visible light (≥410 nm) in aqueous acetonitrile released the corresponding carboxylic acids in high chemical (94-97%) and quantum (0.072-0.093) yields. The results obtained from the photolysis of the caged ester in different solvents indicated that solvent has influence on the rate of photorelease. Further, we also explored the ability of FPRPG, perylen-3-ylmethyl for the protection of alcohols and phenols.
- Jana, Avijit,Ikbal, Mohammed,Singh, N.D. Pradeep
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experimental part
p. 1128 - 1136
(2012/02/16)
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- A mild method for the cleavage of the 4-picolyloxy group with magnesium under neutral conditions
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A mild and efficient method for the selective hydrolysis of 4-picolyl esters with magnesium in methanol or water in the presence of other esters and sensitive protecting groups is described. 4-Picolyl aryl ethers and thioethers are also smoothly deprotected to give the corresponding phenols and thiophenols. Georg Thieme Verlag Stuttgart. New York.
- Zhu, Jianwei,Miao, Wenjun,Bao, Lingling,Ji, Tao,Tang, Guo,Xu, Pengxiang,Zhao, Yufen
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supporting information; experimental part
p. 142 - 144
(2012/02/04)
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- Guanidine hydrochloride as an organocatalyst for N-Boc protection of amino groups
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A simple and efficient method for the chemoselective N-Boc protection of the amine moiety in a variety of compounds is described using di-tert-butyl dicarbonate and guanidine hydrochloride as an organocatalyst in ethanol at 35-40°C. Selective mono-N-Boc protection of diamines and chemoselective protection of hydroxylamines without formation of any side products is achieved. Amino acids and peptides are N-Boc protected efficiently in excellent yields under convenient reaction conditions.
- Jahani, Fatemeh,Tajbakhsh, Mahmood,Golchoubian, Hamid,Khaksar, Samad
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supporting information; experimental part
p. 1260 - 1264
(2011/04/15)
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- An efficient and highly chemoselective N-Boc protection of amines, amino acids, and peptides under heterogeneous conditions
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A simple and efficient procedure for chemoselective mono-N-Boc protection of various structurally diverse amines, amino acids, and peptides with di-tert-butyl dicarbonate using Amberlyst-15 as catalyst in ethanol is described. The catalyst can be readily separated from the reaction products with simple filtration and recovered for direct reuse. No competitive side-reactions such as formation of isocyanate, urea, oxazolidinone, and N,N-di-Boc derivatives were observed.
- Jahani, Fatemeh,Tajbakhsh, Mahmood,Khaksar, Samad,Azizi, Mohamad Reza
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experimental part
p. 1035 - 1043
(2012/07/27)
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- Design, synthesis and primary activity assay of tripeptidomimetics as histone deacetylase inhibitors with linear linker and branched cap group
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A novel series of tripeptidomimetics with spiro ring containing sulfur atoms as cap group and linear carbochain as linker was designed and synthesized as HDACs inhibitors. Several compounds possessed more potent HDAC8 inhibitory activity than clinically used drug SAHA, although their HDAC1 inhibitory activities and anti-proliferative activities against human breast cancer cell lines (MCF-7, MDA-MB-231) and prostate cancer cell line (PC-3) were not satisfactory. Among them, compounds 11l and 11k showed excellent potency against HDAC8 (IC50 values were 0.021 ± 0.004 μM and 0.035 ± 0.007 μM, respectively, whereas SAHA was 0.70 ± 0.12 μM), and good selectivity over HDAC1. Up to now, few hydroxamic acid derivatives with linear linker were reported to possess HDAC8 selectivity over HDAC1.
- Zhang, Yingjie,Feng, Jinhong,Jia, Yuping,Xu, Yingying,Liu, Chunxi,Fang, Hao,Xu, Wenfang
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experimental part
p. 5387 - 5397
(2011/12/14)
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- Benzotriazole reagents for the syntheses of Fmoc-, Boc-, and Alloc-protected amino acids
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Stable Fmoc-, Boc-, and Alloc-benzotriazoles react with various amino acids including unprotected serine and glutamic acid, in the presence of triethylamine at 20° as reagents to introduce -amino protecting groups to afford Fmoc-, Boc-, and Alloc-protected amino acids (77-94%) free of dipeptide and tripeptide impurities. Fmoc-, and Alloc-Gly-Gly-OH dipeptides were prepared in 90% yields by N-acylation of glycylglycine with Fmoc- and Alloc-benzotriazoles in the presence of triethylamine. Synthesized N-protected amino acids were greater than 99% pure, analyzed by HPLC. Georg Thieme Verlag Stuttgart - New York.
- Ibrahim, Tarek S.,Tala, Srinivasa R.,El-Feky, Said A.,Abdel-Samii, Zakaria K.,Katritzky, Alan R.
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supporting information; experimental part
p. 2013 - 2016
(2011/10/08)
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- Concise total synthesis and stereochemical revision of (+)-naseseazines A and B: Regioselective arylative dimerization of diketopiperazine alkaloids
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Concise and enantioselective total syntheses of (+)-naseseazines A and B are described. Our regioselective and directed dimerization of diketopiperazines provides their critical C3-Csp2 linkages, an assembly with plausible biogenetic relevance. We revise the absolute stereochemistry of (+)-naseseazines A and B.
- Kim, Justin,Movassaghi, Mohammad
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p. 14940 - 14943
(2011/11/04)
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