- Clickable glycopeptoids for synthesis of glycopeptide mimic
-
Structurally diverse novel glycopeptoids were synthesized which can be attached to biologically important peptides by click reaction to improve their potential to be used in medicinal chemistry. Triazole-linked αβ-hydrid glycopeptoids were synthesized that mimic the conserved linkage region of N-linked glycoproteins in eukaryotes. The amide bonds were replaced with triazole rings, and αβ-hybrid peptoids were introduced as the backbone modification in peptidomimetics. In addition to their facile synthesis, these modifications have the possibility of introducing otherwise impossible conformations in the peptide backbone.
- Singhamahapatra, Anadi,Sahoo, Laxminarayan,Loganathan, Duraikkannu
-
-
Read Online
- Synthesis and Conformational Analysis of Aminopyrazolonyl Amino Acid (APA)/Peptides
-
Pyrazole, pyrazolone, and aminopyrazolone derived molecules are bioactive molecules and considered as potential therapeutic drug candidates because of their unique structural properties. These molecules have abilities to interact with several bio-macromolecules via non-covalent interactions such as hydrogen bonding and π–π interactions. In structural organization of dipeptides, pyrazole containing aromatic amino acid/dipeptides have been explored and considered as potential amino acid residue. In repertoire of unnatural aromatic amino acids, this report describes the synthesis of 4-aminopyrazolonyl containing amino acids and their crystal structures. The incorporation of 4-aminopyrazolonyl at N-terminal of native amino acid/dipeptides influences the conformational changes of respective peptide which induces the formation of distinctive supramolecular self-assembly structures such as β-sheet and α-helices in their solid-state crystal. The structural conformation of those peptides, here, are also demonstrated in solution phase by 1H-NMR (1D/2D) and [D6]DMSO titration methods which support the formation of inter-/intramolecular hydrogen bonding in solution. Hence, these unnatural amino acid analogues can tune the secondary structure of natural amino acid/peptides by introducing at N-terminal via amide bond.
- Bollu, Amarnath,Sharma, Nagendra K.
-
-
Read Online
- Synthesis of Ethyl cis-2--7-oxo-3-phenyl-6-phthalimido-1-azabicyclohept-3-ene-2-carboxylate and Methyl cis-2-Bromo-3-methyl-8-oxo-7-phthalimido-4-oxa-1-azabicyclooctane-2-carboxylate
-
Th synthesis of Δ1-carbapenem and two β-lactams possessing a Br-atom at the N-substituting center not involved in the lactam ring and bearing the carboxyl group is described.The β-lactams having this kind of Br-substitution are more susceptible to nucleophilic attack than those having a conjugated double bond with the N-atom of the β-lactam ring.DBU is found to be an excellent reagent for the elimination of the silyloxy function.Moreover, a simple method for the addition of diethyl phosphite to an α,β-unsaturated double bond using a catalytic amount of NaH is described.
- Hakimelahi, Gholam H.,Jarrahpour, Ali A.
-
-
Read Online
- NOVEL TRITERPENE DERIVATIVES AS HIV INHIBITORS
-
The present invention relates to novel triterpene derivatives of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, n, and ring (II) are as defined in formula (I). The invention also relates to novel triterpene derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
- -
-
Page/Page column 51
(2021/08/20)
-
- Visible-Light Mediated Tryptophan Modification in Oligopeptides Employing Acylsilanes
-
A method for the selective tryptophan modification and labelling of tryptophan-containing peptides is described. Photoirradiation of acylsilanes generates reactive siloxycarbenes which undergo H?N-insertion into the indole moiety of tryptophan to give stable silyl protected hemiaminals. This method is successfully applied to chemically modify various tryptophan containing oligopeptides. The method enables the selective introduction of alkynes to peptides that are eligible for further alkyne-azide click chemistry. In addition, the dansyl fluorophore can be conjugated to a peptide using this approach.
- Reimler, Jannik,Studer, Armido
-
supporting information
p. 15392 - 15395
(2021/10/04)
-
- Synthesis method of aztreonam main ring synthesis intermediate N-carbobenzoxy-L-threonine amide
-
The invention provides a synthesis method of aztreonam main ring synthesis intermediate N-carbobenzoxy-L-threonine amide, which comprises the following steps: 1) adding an L-threonine solid and methanol into a reaction kettle, stirring, cooling, dropwisely adding thionyl chloride, carrying out heating reflux reaction, and drying a solvent by distillation; (2) adding methanol into a reactant obtained in the step (1) for dissolving, heating and pressurizing, introducing liquid ammonia, keeping the temperature and the pressure, evaporating the liquid ammonia after the reaction is finished, and evaporating the solvent to dryness; and 3) adding water into a reaction product obtained in the step 2) for dissolving, dropwise adding benzyl chloroformate, dropwise adding an acid-binding agent solution to control the pH value of the reaction system to obtain intermediate N-carbobenzoxy-L-threonine amide, and carrying out filter pressing and drying to obtain a solid.
- -
-
Paragraph 0018-0024
(2020/05/01)
-
- NOVEL TRITERPENE DERIVATIVES AS HIV INHIBITORS
-
The present invention relates to novel triterpene derivatives of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and ring are as defined herein. The invention also relates to novel triterpene derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
- -
-
Page/Page column 34
(2020/08/28)
-
- Catalytic Mechanism Study on the 1,2- and 1,4-Transfer Hydrogenation of Ketimines and β-Enamino Esters Catalyzed by Axially Chiral Biscarboline-Based Alcohols
-
Axial N-O alcohols, which have two large carboline moieties connected to the axis were synthesized and used in catalytic enantioselective 1,2- and 1,4-transfer hydrogenations of total 26 ketimines and β-enamino esters. Excellent levels of enantioselectivity ranging from 91% to 99% were achieved by using catalyst (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. Interestingly, a mixture of (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide and (aR)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide was also able to provide high enantioselectivities up to 95% that is the same as that using pure (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. A plausible catalytic mechanism was suggested and total four kinds of transition states (TS) including almost 60 TS structures were investigated using density functional theory (DFT) with different basis sets such as 6-311G(2d,p). The predicted activation energy data are consistent with the experimental results. (Figure presented.).
- Dong, Mengxian,Wang, Jie,Wu, Shijie,Zhao, Yang,Ma, Yangyang,Xing, Yongfei,Cao, Fei,Li, Longfei,Li, Zhenqiu,Zhu, Huajie
-
supporting information
p. 4602 - 4610
(2019/08/30)
-
- PROCESS AND INTERMEDIATES FOR SYNTHESIS OF PEPTIDE COMPOUNDS
-
Disclosed is a new process and intermediates for preparing dipyrrolidine peptide compounds such as, for example, rapastinel. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.
- -
-
Paragraph 0170
(2019/02/13)
-
- Synthesis method of aztreonam monocyclic mother nucleus
-
The invention discloses a synthesis method of an aztreonam monocyclic mother nucleus, and mainly relates to the technical field of pharmaceutical and chemical industry. The method comprises the stepsthat L-threonine is subjected to methyl esterification; terbutyloxycarbonyl anhydride is used for performing amino BOC protection; ammonia water is subjected to ammonolysis; under the catalysis of a solid basic catalyst, methyl-sulfuric-acyl reaction and sulfonation are performed; cyclization, deprotection and acidification are performed to obtain the aztreonam monocyclic mother nucleus. The raw materials are cheap and can be easily obtained; the yield is high; the cost is low; the synthesis method belongs to a green, energy-saving and environment-friendly practical technology.
- -
-
Paragraph 0046; 0047
(2019/06/13)
-
- Synthesis and evaluation of in vivo anti-hypothermic effect of all stereoisomers of the thyrotropin-releasing hormone mimetic: Rovatirelin Hydrate
-
We discovered the orally active thyrotropin-releasing hormone (TRH) mimetic: (4S,5S)-5-methyl-N-{(2S)-1-[(2R)-2-methylpyrrolidin-1-yl]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl}-2-oxo-1,3-oxazolidine-4-carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100-fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti-hypothermic effect of all stereoisomers of 1, which has the (4S),(5S),(2S),(2R) configuration from the N-terminus to the C-terminus, in order to clarify the structure?activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)-isomer 16 did not show any anti-hypothermic effect. Only the (4S),(5S),(2S),(2S)-isomer 10, which has the (2S)-2-methylpyrrolidine moiety at the C-terminus showed the anti-hypothermic effect similar to 1. Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N-terminus and the (2R) configuration at the middle-part, showed a much lower anti-hypothermic effect than that of 1. On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N-terminus or the (2S) configuration of the C-terminus, have little influence on the anti-hypothermic effect.
- Kobayashi, Naotake,Sato, Norihito,Sugita, Katsuji,Takahashi, Kouji,Sugawara, Tamio,Tada, Yukio,Yoshikawa, Takayoshi
-
-
- Preparation method of O-methyl-threonine/tyrosine
-
The invention relates to a preparation method of O-methyl-threonine/tyrosine. The preparation method mainly overcomes the disadvantages of the existing method that a toxic reagent is volatile, the reagent is dangerous, the steps are long, the yield is low, and the like. The preparation method of the O-methyl-threonine/tyrosine comprises the following steps: N-t-butyloxycarboryl-threonine/tyrosineis catalyzed by sodium hydroxide and reacts with dimethyl sulfate to generate N-t-butyloxycarboryl-O-methyl-threonine/tyrosine, and then t-butyloxycarboryl is removed from the N-t-butyloxycarboryl-O-methyl-threonine/tyrosine through acid substances to obtain the product O-methyl-threonine/tyrosine. The product has important application in the fields of antibiotics and polypeptide drugs.
- -
-
Paragraph 0013
(2018/06/21)
-
- Serine- and threonine-derived diamine equivalents for site-specific incorporation of platinum centers in peptides, and the anticancer potential of these conjugates
-
A modular strategy that allows introduction of one or more reactive platinum units at chosen locations along a peptide sequence is presented. This makes use of diazides generated from serine and threonine as diamine equivalents which can be conjugated to the peptide under standard coupling conditions. Reduction of these diazides using Pd/C and H2 followed by platination affords the final products in good yields. Following this, we prepared a new class of peptide-platinum conjugates and carried out preliminary cytotoxicity evaluation and DNA interaction studies. Inclusion of lysine residues in the sequence was found to improve DNA interaction and anticancer activities compared to analogous conjugates with hydrophobic side chains.
- Kumbhakonam, Sateeshkumar,Vellaisamy, Kasipandi,Saroj, Soumya,Venkatesan, Nalini,Karunagaran,Manheri, Muraleedharan Kannoth
-
p. 2450 - 2458
(2018/02/19)
-
- Catenulobactins A and B, Heterocyclic Peptides from Culturing Catenuloplanes sp. with a Mycolic Acid-Containing Bacterium
-
The production of two new heterocyclic peptide isomers, catenulobactins A (1) and B (2), in cultures of Catenuloplanes sp. RD067331 was significantly increased when it was cocultured with a mycolic acid-containing bacterium. The planar structures and absolute configurations of the catenulobactins were determined based on NMR/MS and chiral-phase GC-MS analyses. Catenulobactin B (2) displayed Fe(III)-chelating activity and moderate cytotoxicity against P388 murine leukemia cells.
- Hoshino, Shotaro,Ozeki, Masahiro,Awakawa, Takayoshi,Morita, Hiroyuki,Onaka, Hiroyasu,Abe, Ikuro
-
supporting information
p. 2106 - 2110
(2018/09/12)
-
- Unveiling and tackling guanidinium peptide coupling reagent side reactions towards the development of peptide-drug conjugates
-
Peptide coupling reagents and especially uronium/guanidinium salts have been extensively utilized in solid-phase peptide synthesis. However, the impact of these reagents in solution phase synthesis, normally used in the formation of peptide-drug conjugates (PDCs), has not been fully explored. Herein, we identified that when guanidinium salts are used in classical peptide coupling conditions, besides leading to the formation of amide bonds, a uronium derivative can also be installed on specific amino acid scaffolds. The formation of this side product depends on the reaction conditions, as also on the nucleophilicity of the susceptible groups. Conditions to avoid this side product formation and a putative reaction mechanism describing its formation are reported.
- Vrettos, Eirinaios I.,Sayyad, Nisar,Mavrogiannaki, Eftychia M.,Stylos, Evgenios,Kostagianni, Androniki D.,Papas, Serafim,Mavromoustakos, Thomas,Theodorou, Vassiliki,Tzakos, Andreas G.
-
p. 50519 - 50526
(2017/11/10)
-
- PROCESSES FOR SYNTHESIS OF DIPYRROLIDINE PEPTIDE COMPOUNDS
-
Disclosed is a new process for preparing dipyrrolidine peptide compounds such as, for example, GLYX-13. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.
- -
-
Paragraph 00103-00106
(2017/12/27)
-
- Halofluorination of N-protected α,β-dehydro-α-amino acid esters—A convenient synthesis of α-fluoro-α-amino acid derivatives
-
N-protected dehydroamino acid methyl esters have been converted to α-fluoro-β-halo amino acid derivatives under halofluorination reaction conditions. The influences of the nitrogen protecting group of the substrates and of the halonium electrophile on the reaction outcome and the stability of the obtained products have been studied. Furthermore, reduction of the halogen substituent (Cl or Br) under radical conditions provided a possibility for follow-up reactions. Nucleophilic substitution reactions, however, failed.
- Ulbrich, Dirk,Daniliuc, Constantin G.,Haufe, Günter
-
supporting information
p. 65 - 75
(2016/07/11)
-
- Ammonia curved the monocyclic parent nucleus method for the preparation of
-
The invention relates to a preparation of Aztreonam monocyclic parent nucleus method, in the method using benzyl chloroformate under strongly acidic conditions the protection, the sodium carbonate is used to carry out closed-loop reaction, the reaction is stable, is greatly improved yield, total yield of 48% the advantages.
- -
-
Paragraph 0030; 0031
(2017/01/26)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 00109; page 39
(2014/08/19)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 0106
(2014/08/19)
-
- HR-MALDI-MS imaging assisted screening of β-Carboline alkaloids discovered from mycena metata
-
Fruiting bodies of Mycena metata were screened for the presence of new secondary metabolites by means of HPLC-UV, LC-HR-ESIMS, and high-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (HRMALDI- MS imaging). Thus, a new β-carboline alkaloid, 6-hydroxymetatacarboline D (1d), was isolated from fruiting bodies of M. metata. 6-Hydroxymetatacarboline D consists of a highly substituted β-carboline skeleton, which is likely to be derived biosynthetically from L-tryptophan, 2-oxoglutaric acid, L-threonine, and L-proline. The structure of the alkaloid was established by 2D NMR spectroscopic methods and HR-ESIMS. Moreover, by extensive application of LC-HR-ESIMS, LC-HR-ESIMS/MS, and LC-HR-ESIMS3 techniques we were able to elucidate the structures of a number of accompanying β-carboline alkaloids, 1a- 1c, 1e-1i, and 2a-2g, structurally closely related to 6-hydroxymetatacarboline D, which are present in M. metata in minor amounts. The absolute configuration of the stereogenic centers of the β-carboline alkaloids was determined by GC-MS comparison with authentic synthetic samples after hydrolytic cleavage and derivatization of the resulting amino acids.
- Jaeger, Robert J. R.,Lamshoeft, Marc,Gottfried, Sebastian,Spiteller, Michael,Spiteller, Peter
-
p. 127 - 134
(2013/06/27)
-
- Comparison of liquid chromatography-isotope ratio mass spectrometry (LC/IRMS) and gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) for the determination of collagen amino acid δ13C values for palaeodietary and palaeoecological reconstruction
-
Results are presented of a comparison of the amino acid (AA) δ13C values obtained by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) and liquid chromatography-isotope ratio mass spectrometry (LC/IRMS). Although the primary focus was the compound-specific stable carbon isotope analysis of bone collagen AAs, because of its growing application for palaeodietary and palaeoecological reconstruction, the results are relevant to any field where AA δ13C values are required. We compare LC/IRMS with the most up-to-date GC/C/IRMS method using N-acetyl methyl ester (NACME) AA derivatives. This comparison involves the analysis of standard AAs and hydrolysates of archaeological human bone collagen, which have been previously investigated as N-trifluoroacetyl isopropyl esters (TFA/IP). It was observed that, although GC/C/IRMS analyses required less sample, LC/IRMS permitted the analysis of a wider range of AAs, particularly those not amenable to GC analysis (e.g. arginine). Accordingly, reconstructed bulk δ13C values based on LC/IRMS-derived δ13C values were closer to the EA/IRMS-derived δ13C values than those based on GC/C/IRMS values. The analytical errors for LC/IRMS AA δ13C values were lower than GC/C/IRMS determinations. Inconsistencies in the δ13C values of the TFA/IP derivatives compared with the NACME- and LC/IRMS-derived δ13C values suggest inherent problems with the use of TFA/IP derivatives, resulting from: (i) inefficient sample combustion, and/or (ii) differences in the intra-molecular distribution of δ13C values between AAs, which are manifested by incomplete combustion. Close similarities between the NACME AA δ13C values and the LC/IRMS-derived δ13C values suggest that the TFA/IP derivatives should be abandoned for the natural abundance determinations of AA δ13C values.
- Dunn, Philip J. H.,Honch, Noah V.,Evershed, Richard P.
-
experimental part
p. 2995 - 3011
(2012/05/20)
-
- Synthesis of the N-(tert-butyloxycarbonyl)-O-triisopropylsilyl-d- pyrrolosamine glycal of lomaiviticins A and B via epimerization of l-Threonine
-
An efficient synthesis of the N-(tert-butyloxycarbonyl)-O- triisopropylsilyl-d-pyrrolosamine glycal of lomaiviticin A (1) and lomaiviticin B (2) is described. The synthesis is highlighted by the epimerization of the l-threonine-derived oxazolidine 10 to oxazolidine 11. This key epimerization reaction, which serves to establish the correct relative configuration of the carbohydrate unit, was made possible only after conformational analysis indicated that substituted oxazolidines may adopt conformations that preclude enolization.
- Morris, William J.,Shair, Matthew D.
-
scheme or table
p. 4310 - 4312
(2010/09/20)
-
- Biomimetic synthesis of esters of natural amino acids
-
A method for the synthesis of Gly, Ala, Phe, and Thr esters is proposed and considered as being a stage of possible biomimetic synthesis of peptides. The methyl esters of the said amino acids are obtained via intervention of 2-hydroxypropyl phosphonate. The resulting aminoacyl phosphonates reacts with methanol to produce the amino acid methyl esters, with the release of phosphoric acid. The reaction is carried out at room temperature in water.
- Devedjiev, Ivan T.,Bairyamov, Stanislav G.,Videva, Vladimira S.
-
p. 252 - 255
(2008/09/19)
-
- Coibamide A, a potent antiproliferative cyclic depsipeptide from the panamanian marine cyanobacterium Leptolyngbya sp.
-
Coibamide A (1) is a new, potent antiproliferative depsipeptide which was isolated from a marine Leptolyngbya cyanobacterium collected from the Coiba National Park, Panama. The planar structure of 1 was elucidated by a combination of NMR spectroscopy and mass spectrometry. Exhaustive 1D and 2D NMR spectroscopy included natural abundance 15N and variable temperature experiments; mass spectrometry included TOF-ESI-MSn and FT-MSn experiments. Chemical degradation followed by chiral HPLC- and GC-MS analyses was used to assign the absolute configuration of 1. This highly methylated cyclized depsipeptide exhibited an unprecedented selectivity profile in the NCI 60 cancer cell line panel and appears to act via a novel mechanism. Copyright
- Medina, Rebecca A.,Goeger, Douglas E.,Hills, Patrice,Mooberry, Susan L.,Huang, Nelson,Romero, Luz I.,Ortega-Barria, Eduardo,Gerwick, William H.,McPhail, Kerry L.
-
p. 6324 - 6325
(2008/12/22)
-
- Design, synthesis, and bioactivity of novel inhibitors of E. coli aspartate transcarbamoylase
-
A series of inhibitors of the aspartate transcarbamoylase, an enzyme involved in pyrimidine nucleotide biosynthesis, has been synthesized. These inhibitors are analogues of a highly potent inhibitor of this enzyme, N-phosphonacetyl-l-aspartate (PALA). Analogues have been synthesized with modifications at the α- and β-carboxylates as well as at the aspartate moiety. The ability of these compounds to inhibit the enzyme was evaluated. These studies, with functional group modified PALA derivatives, showed that amide groups can be a useful substitute of the carboxylate in order to reduce the charge on the molecule, and indicate that the relative position of the functional group in the β-position is more critical than the nature of the functional group. Some of the molecules synthesized here are potent inhibitors of the enzyme.
- Eldo, Joby,Heng, Sabrina,Kantrowitz, Evan R.
-
p. 2086 - 2090
(2007/10/03)
-
- Synthesis of bisaminoacylated pdCpAs and tandemly activated transfer RNAs
-
Described herein is the preparation of new bisacylated tRNAs and their participation in protein synthesis. It has been reported that Thermus thermophilus phenylalanyl-tRNA synthetase can introduce two phenylalanine moieties onto the 3′-terminal adenosine of its cognate tRNA. It is also possible to prepare bisactivated tRNAs in vitro; these participate in protein synthesis [Wang, B.; Zhou, J.; Lodder, M.; Anderson, R. D.; Hecht, S. M. J. Biol. Chem. 2006, 281, 13865]. Presently, the chemical strategy used for the synthesis of the key intermediate bisacylated pdCpAs is described. Bis-S-alanyl- and bis-S-methionyl-pdCpAs were prepared initially. Further, S-threonine, S-allo-threonine, S-homoserine, and (S)-(+)-2-amino-3-hydroxy-3-methylbutyric acid were coupled with the dinucleotide to define preparative methods applicable to more complex amino acids bearing additional functionality in the form of an OH group.
- Duca, Maria,Maloney, David J.,Lodder, Michiel,Wang, Bixun,Hecht, Sidney M.
-
p. 4629 - 4642
(2008/03/13)
-
- Stereoselective synthesis and anti-inflammatory activities of 6- and 7-membered dioxacycloalkanes
-
A class of 5-trifluoroacetylamino-1,3-dioxacycloalkanes, 5-benzoylamino-1,3-dioxacycloalkanes, and 5-amino-1,3-dioxacycloalkane compounds were stereoselectively synthesized as potential anti-inflammatory drug candidates. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model, from which multiple compounds possessing anti-inflammatory properties which surpass aspirin were identified; these compounds were then compared to establish structure-activity relationships.
- Gu, Keli,Bi, Lanrong,Zhao, Ming,Wang, Chao,Dolan, Cheryl,Kao, Michael C.,Tok, Jeffrey B.-H.,Peng, Shiqi
-
p. 1339 - 1347
(2007/10/03)
-
- Synthesis of (2R,3S) 3-amino-4-mercapto-2-butanol, a threonine analogue for covalent inhibition of sortases
-
L-Threonine 2 was converted in seven steps into the protected aminomercaptoalcohol 8, a threonine mimic. This compound 8 was coupled to various oligopeptides to produce two different tetrapeptide analogues, for example, 11 and 17, which were shown to inhibit the Sortase enzymes (SrtA and SrtB) via covalent attachment of the thiol groups of 11 and 17 to the catalytically active cysteine residue of the Sortase enzymes.
- Jung, Michael E.,Clemens, Jeremy J.,Suree, Nuttee,Liew, Chu Kong,Pilpa, Rosemarie,Campbell, Dean O.,Clubb, Robert T.
-
p. 5076 - 5079
(2007/10/03)
-
- Total Synthesis of the Depsipeptide FR-901375
-
The first total synthesis of FR-901375, a novel bicyclic depsipeptide isolated from the fermentation broth of Pseudomonas chloroaphis No. 2522, has been achieved. The synthetic approach involves 13 reaction steps and is achieved in 12% overall yield. The key points in the successful synthetic strategy are a concise asymmetric synthesis of the key building block (3R,4E)-3-hydroxy-7-mercapto-4-heptenoic acid, a mild Mitsunobu macrolactonization step, and an I2-mediated deprotection with concomitant disulfide-bridge formation.
- Chen, Yanping,Gambs, Celine,Abe, Yoshito,Wentworth Jr., Paul,Janda, Kim D.
-
p. 8902 - 8905
(2007/10/03)
-
- A new stereoselective approach to β-hydroxy-α-aminoacids and dipeptides
-
The chiral synthons 1, 2 and 1' were submitted to aldol condensation to achieve both β-hydroxy-α-aminoacids and dipeptides. The configuration of the new stereogenic centers was assigned on the basis of 1H NMR spectroscopic data.
- Di Felice, Pina,Porzi, Gianni,Sandri, Sergio
-
p. 2191 - 2201
(2007/10/03)
-
- Papuamides A-D, HIV-inhibitory and cytotoxic depsipeptides from the sponges Theonella mirabilis and Theonella swinhoei collected in Papua New Guinea
-
The novel cyclic depsipeptides papuamides A (1), B (2), C (3), and D (4) have been isolated from Papua New Guinea collections of the sponges Theonella mirabilis and Theonella swinhoei. Their structures were determined by a combination of spectroscopic analysis and chemical degradation and derivatization studies. In addition to glycine, alanine, and threonine, these peptides contain a number of unusual amino acids including 3,4- dimethylglutamine, β-methoxytyrosine, 3-methoxyalanine, and 2,3- diaminobutanoic acid or 2-amino-2-butenoic acid residues. Papuamides A-D (1- 4) are also the first marine-derived peptides reported to contain 3- hydroxyleucine and homoproline residues. These peptides also contain a previously undescribed 2,3-dihydroxy-2,6,8-trimethyldeca-(4Z,6E)-dienoic acid moiety N-linked to a terminal glycine residue. Papuamides A (1) and B (2) inhibited the infection of human T-lymphoblastoid cells by HIV-1(RF) in vitro with an EC50 of approximately 4 ng/mL. Compound 1 was also cytotoxic against a panel of human cancer cell lines with a mean IC50 of 75 ng/mL.
- Ford, Paul W.,Gustafson, Kirk R.,McKee, Tawnya C.,Shigematsu, Nobuharu,Maurizi, Laura K.,Pannell, Lewis K.,Williams, David E.,De Silva, E. Dilip,Lassota, Peter,Allen, Theresa M.,Van Soest, Rob,Andersen, Raymond J.,Boyd, Michael R.
-
p. 5899 - 5909
(2007/10/03)
-
- Synthesis of a new serine containing glycotetrapeptide from Mycobacterium xenopi glycopeptidolipid : An unusual structural variant in mycobacterium genus
-
Synthesis of the unique glycotetrapeptide segment of Mycobacterium xenopi glycopeptidolipid is described.
- Gurjar, Mukund K.,Saha, Uttam K.
-
p. 4979 - 4982
(2007/10/02)
-
- 1,4-dihydropyridine-threonine compounds with cardiovascular activity
-
Cardioactive dihydropyridines of the formula STR1 in which Y is STR2 A is H or CH3, B is --NH, --NH--CO--, --NH--CS--, --NH--COO--, --NH--SO2 --or --NH--CO--NH-- or --NH--CS--NH--, and R13 and R14 each independently is H or an organic radical, and salts thereof. The Y can be hydrolyzed off. The other radicals on the dihydropyridine moiety can also be varied.
- -
-
-
- ENANTIOSELECTIVE SYNTHESIS OF NON-PROTEINOGENIC AMINO ACIDS VIA METALLATED BIS-LACTIM ETHERS OF 2,5-DIKETOPIPERAZINES
-
Bis-lactim ethers 1 of 2,5-diketopiperazines contain a chiral inducing center, an acidic CH-bond and two sites susceptible to hydrolysis.They react with BuLi to give Li compounds of type 4, 15, 29 or 32, which possess a prochiral C atom.They readily add electrophiles (such as alkylating agents or carbonyl compounds) with unusually high diastereoface differentiation.In many cases the d.e-value (d.e. = diastereomeric excess = asymmetric induction) of the adduct exceeds 95percent.On hydrolysis the adducts are cleaved liberating the chiral auxiliary (used to build up the bis-lactim ether 1) and the target molecules, the optically active amino acid methyl esters of type 8, 19, 25 or 36.The two amino acid esters are separable either by fractional distillation or (eventually after further hydrolysis to amino acids) by chromatography.Transition state models are discussed that could explain the exceptionally high asymmetric induction and the predictability of the induced configuration.
- Schoellkopf, Ulrich
-
p. 2085 - 2092
(2007/10/02)
-