- RETRACTED ARTICLE: Asymmetric Synthesis of Apratoxin e
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An efficient method for asymmetric synthesis of apratoxin E 2 is described in this report. The chiral lactone 8, recycled from the degradation of saponin glycosides, was utilized to prepare the non-peptide fragment 6. In addition to this "from nature to nature" strategy, olefin cross-metathesis (CM) was applied as an alternative approach for the formation of the double bond. Moreover, pentafluorophenyl diphenylphosphinate was found to be an efficient condensation reagent for the macrocyclization.
- Mao, Zhuo-Ya,Si, Chang-Mei,Liu, Yi-Wen,Dong, Han-Qing,Wei, Bang-Guo,Lin, Guo-Qiang
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Read Online
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
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Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders as well as other disorders.
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Page/Page column 36
(2019/08/26)
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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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- Controlled ring-opening polymerization of α-amino acid N-carboxy-anhydride by frustrated amine/borane Lewis pairs
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In this communication, we presented a novel strategy to control the ROP of α-amino acid N-carboxy-anhydrides using the concept of frustrated Lewis pairs (FLPs). An FLP intermediate containing an interaction between the bulky borane Lewis acid and the amine groups of the propagation chain end is essential to accomplish the polypeptide synthesis with well-defined structures under mild conditions.
- Zhang, Hongyuan,Nie, Yanzhao,Zhi, Xinmei,Du, Haifeng,Yang, Jing
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supporting information
p. 5155 - 5158
(2017/07/12)
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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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- DRUG DERIVATIVES
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The present invention relates to derivatives of known active pharmaceutical compounds. These derivatives are differentiated from the parent active compound by virtue of being redox derivatives of the active compound. This means that one or more of the functional groups in the active compound has been converted to another group in one or more reactions which may be considered to represent a change of oxidation state. We refer to these compounds generally as redox derivatives. The derivatives of the invention may be related to the original parent active pharmaceutical compound by only a single step transformation, or may be related via several synthetic steps including one or more changes of oxidation state. In certain cases, the functional group obtained after two or more transformations may be in the same oxidation state as the parent active compound (and we include these compounds in our definition of redox derivatives). In other cases, the oxidation state of the derivative of the invention may be regarded as being different from that of the parent compound. In many cases, the compounds of the invention have inherent therapeutic activity on their own account. In some cases, this activity relative to the same target or targets of the parent compound is as good as or better than the activity which the parent compound has against the target or targets.
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Paragraph 0425; 0426
(2013/09/12)
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- DRUG DERIVATIVES
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The present invention relates to derivatives of known active pharmaceutical compounds. These derivatives are differentiated from the parent active compound by virtue of being redox derivatives of the active compound. This means that one or more of the functional groups in the active compound has been converted to another group in one or more reactions which may be considered to represent a change of oxidation state. We refer to these compounds generally as redox derivatives. The derivatives of the invention may be related to the original parent active pharmaceutical compound by only a single step transformation, or may be related via several synthetic steps including one or more changes of oxidation state. In certain cases, the functional group obtained after two or more transformations may be in the same oxidation state as the parent active compound (and we include these compounds in our definition of redox derivatives). In other cases, the oxidation state of the derivative of the invention may be regarded as being different from that of the parent compound. In many cases, the compounds of the invention have inherent therapeutic activity on their own account. In some cases, this activity relative to the same target or targets of the parent compound is as good as or better than the activity which the parent compound has against the target or targets.
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Page/Page column 115
(2012/05/31)
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- Synthesis and biological evaluation of boron peptide analogues of Belactosin C as proteasome inhibitors
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A series of boron peptides 11, 13, 15 and 17 were designed and synthesized as proteasome inhibitors based on the structure of Belactosin C. Matteson homologation was a key step in the synthesis of the boron peptides. Compounds 11a and 13 showed significant inhibition of 20S proteasome chymotrypsin-like (β5) activity (IC50 = 0.28 and 0.51 μM, respectively). Furthermore, like PS-341, compound 11a increased the G2/M cell distribution. A biparametric cytofluorimetric analysis with FITC-labeled annexin V and propidium iodide showed induction of apoptosis by compound 11a at >1 μM concentrations of compound.
- Nakamura, Hiroyuki,Watanabe, Mizuyoshi,Ban, Hyun Seung,Nabeyama, Wataru,Asai, Akira
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scheme or table
p. 3220 - 3224
(2010/04/05)
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- NOVEL INTEGRIN BINDING RGD-LIPOPEPTIDES WITH GENE TRANSFER ACTIVITIES
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The present invention provides synthesis of a novel series of cationic lipopeptides with integrin-binding RGD functionalities. The invention also provides phenomenally high L27 (transformed Sl 80, mouse sarcoma cells) cell tropic gene transfer properties of these novel RGD-lipopeptides. Since L27 cell surface contains over expressed integrins, the present class of lipopeptides with integrin-binding RGD ligands are likely to find future applications in targeting anti-cancer genes/drugs to the endothelial cells of tumor vasculatures (possessing over expressed integrins).
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Page/Page column 22
(2008/06/13)
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- Design and synthesis of all diastereomers of cyclic pseudo-dipeptides as mimics of cyclic CXCR4 pentapeptide antagonists
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The four diastereomers of 2,5-bis[(3-guanidino)propyl]-1-[3-(4- hydroxyphenyl)propionyl]-7-(2-naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (54-57) and of 2,5-bis[(3-guanidino)propyl]-1-(4-hydroxyphenylacetyl)-7-(2- naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (58-61) were synthesized by a divergent methodology from l- and d-glutamic acids. The 11-membered ring core was made by ring closing metathesis of linear bis(allylamines), and the guanidyl functions were introduced by a simultaneous double Mitsunobu reaction using bis(Boc)guanidine. These compounds were designed to mimic cyclic pentapeptide FC131 (c[Gly-d-Tyr-Arg-Arg-Nal]). The Royal Society of Chemistry.
- Cluzeau, Jerome,Oishi, Shinya,Ohno, Hiroaki,Wang, Zixuan,Evans, Barry,Peiper, Stephen C.,Fujii, Nobutaka
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p. 1915 - 1923
(2008/02/10)
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- Enzymatic removal of carboxyl protecting groups. III. Fast removal of allyl and chloroethyl esters by Bacillus subtilis esterase (BS2)
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(Chemical Equation Presented) An esterase from Bacillus subtilis (BS2) allows the fast and selective removal of allyl, 2-chloroethyl, and 2,2,2-chloroethyl esters under mild conditions in high yields. In addition, BS2 easily hydrolyzes phenacyl esters, while the hydrolysis of sterically hindered diphenylmethyl esters is slow, requiring longer reaction time and higher enzyme/substrate ratio.
- Fotakopoulou, Irene,Barbayianni, Efrosini,Constantinou-Kokotou, Violetta,Bornscheuer, Uwe T.,Kokotos, George
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p. 782 - 786
(2007/10/03)
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- Synthesis and neuroprotective activity of analogues of glycyl-L-prolyl-L- glutamic acid (GPE) modified at the α-carboxylic acid
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The synthesis of nine GPE* analogues, wherein the α-carboxylic acid group of glutamic acid has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-l-proline 2 with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
- Trotter, Nicholas S.,Brimble, Margaret A.,Harris, Paul W.R.,Callis, David J.,Sieg, Frank
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p. 501 - 517
(2007/10/03)
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- A novel and efficient method for cleavage of phenacylesters by magnesium reduction with acetic acid
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(Equation Presented) In the present study, we use magnesium turnings as a new deprotection reagent for the phenacyl group during orthogonal organic synthesis in the presence of other esters and sensitive protecting groups. By applying the new magnesium turnings/acetic acid deprotection method, phenacyl group can be more easily combined with other protecting groups that are not compatible with the zinc/acetic acid method.
- Kokinaki, Stella,Leondiadis, Leondios,Ferderigos, Nikolas
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p. 1723 - 1724
(2007/10/03)
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- Ready protease-catalyzed synthesis of carbohydrate-amino acid conjugates.
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The protease-catalyzed synthesis of amino acid est-carbohydrate conjugates as glycopeptide analogues has been achieved in a highly regioselective and carbohydrate-specific manner using amino acid vinyl ester acyl donors and minimally or completely unprotected carbohydrate acyl acceptors, which together probed active sites of proteases to reveal yield efficiencies that are modulated by the carbohydrate C-2 substitutent, and that may be exploited to allow selective one-pot syntheses.
- Boyer,Stanchev,Fairbanks,Davis
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p. 1908 - 1909
(2007/10/03)
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- The hydrolysis of primary amide groups in Asn/Gln-containing peptides
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Peptides Boc-Ala-Asn/Gln-OH and Boc-Asn/Gln-Ala-OH were saponified with barium hydroxide to corresponding Asp/Glu-containing peptides. Under the conditions of saponification, Boc-Asn-Ala-OH additionally afforded Boc-Asp-OH, isopeptide Boc-Asp(Ala)-OH, and Boc-NHSuc > Ala-OH, with the third being the key intermediate in these transformations. Boc-Asp(OMe)-Ala-OMe underwent similar transformations under treatment with diazomethane or triethylamine. Saponification with barium hydroxide was accompanied by a high epimerization of N-terminal amino acid residues, whereas the products of the diazomethane treatment of Boc-Asp(OMe)-Ala-OMe had a low degree of epimerization.
- Onoprienko,Yelin,Miroshnikov
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p. 361 - 368
(2007/10/03)
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- Preferential hydrogenolysis of NAP esters provides a new orthogonal protecting group strategy for carboxylic acids
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Selective hydrogenolysis of 2-naphthylmethyl (NAP) esters in the presence of a benzyl ester has been observed with a wide range of dicarboxylic acids. Orthogonal deprotection of NAP esters with challenging substrates can be achieved if the other carboxylic acids in the molecule are protected with 4-trifluoromethyl benzyl group instead of benzyl groups.
- Gaunt, Matthew J.,Boschetti, Carlos E.,Yu, Jinquan,Spencer, Jonathan B.
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p. 1803 - 1806
(2007/10/03)
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- The Chiral Synthesis of Thiazole Amino Acid Enantiomers
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An efficient modified Hantzsch reaction is described for the synthesis of optically pure thiazole amino acid derivatives from the corresponding amino acids.The method is exemplified by the synthesis of a derivative of L-(Gln)Thz, the novel chiral thiazole amino acid moiety of dolastatin 3.The Cotton effects of thiazole amino acids correlate well with the absolute stereochemistry of these compounds.
- Bredenkamp, Martin W.,Holzapfel, Cedric W.,Zyl, Wynand J. van
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p. 2235 - 2249
(2007/10/02)
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- Lyotropic Lipo-Amino-Acids: Synthesis and Structural Study
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Lyotropic lipo-amino-acids Cn(AA) where AA is one of the following amino-acids: glycine, alanine, sarcosine, serine, tyrosine, lysine, hydroxyethylglutamine, hydroxypropylglutamine, hydroxypentylglutamine and glutamic acid, and Cn is a paraffinic chain with 12 or 18 carbon atoms have been synthesized.The study by X-ray diffraction of the lipo-amino-acids in concentrated water solution and in the anhydrous state has shown the existence of two types of mesophases: lamellar and hexagonal.The respective influence of the water concentration, the nature of the amino-acid and the length of the paraffinic chain on the domain of stability of the mesophases and on the values of their structural parameters has been established.
- Gallot, B.,Hassan, H. Haj
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p. 195 - 214
(2007/10/02)
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- Synthesis of a putative subtype specific antigenic heptapeptide from Escherichia coli K88 ad protein fimbriae.
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The heptapeptide methyl ester Phe-Asn-Glu-Asn-Met-Ala-Tyr-OMe covering the amino acid sequence of the region 213-219 of Escherichia Coli K88 ad protein fimbriae is synthesized using N alpha-t-butyloxycarbonyl-protection and benzyl groups for side-chain-protection. All condensation reactions are performed in 84-97% yield by preactivation of the protected amino acids by dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt), and reaction of the resulting active ester with amine in the presence of 4-methylmorpholine (NMM). A mechanism is proposed for the nitrile formation in the side-chain of activated asparagine, and the suppression of this side-reaction is investigated. The repetitive deprotection is performed in a mixture of trifluoroacetic acid (TFA), phenol and p-cresol to give the TFA salts in virtually quantitatively yields. The final deprotection of the heptapeptide is carried out in a mixture of 25% hydrogen fluoride (HF) and dimethyl sulfide (DMS) in an overall yield of 48%. The serological and conformational properties of the synthetic peptide are under investigation.
- Meldal
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p. 242 - 249
(2007/10/02)
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- Synthesis of a putative antigenic heptapeptide from Escherichia coli K88 ab protein fimbriae.
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The heptapeptide Tyr-Arg-Glu-Asp-Met-Glu-Tyr-OMe, spanning region 213-219 of Escherichia coli K88 ab protein fimbriae, was synthesized with an overall yield of 37% using dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) preactivation in all condensation reactions. The C-terminal was protected as the methyl ester. The protection scheme of N alpha-tert-butyloxycarbonyl-(Boc) and benzyl-(Bzl) or benzyloxycarbonyl (Z) groups for side chain protection was found to be orthogonal when a mixture of trifluoroacetic acid (TFA), phenol (PhOH) and p-cresol (CrOH) was used for repetitive deprotection. The final deprotection of Boc-Tyr(Bzl)-Arg(Z2)-Glu(Bzl)-Asp(Bzl)-Met-Glu(Bzl+ ++)-Tyr(Bzl)-OMe (17) was accomplished in 80% yield by prolonged treatment with hydrogen fluoride, dimethyl sulfide, p-cresol and p-thiocresol. The BSA-linked synthetic peptide was used in immunisation experiments on rabbits.
- Meldal
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p. 250 - 256
(2007/10/02)
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- Design of the Synthetic Route for Peptides and Proteins Based on the Solubility Prediction Method. I. Synthesis and Solubility Properties of Human Proinsulin C-Peptide Fragments
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The usefulness of the solubility prediction method is demonstrated using relatively small peptide fragments of human proinsulin C-peptide.The propriety of the solubility prediction method for peptides having polar side chains is also examined in the following respects: (1) Peptide intermediates smaller than a heptapeptide have high solubility regardless of their c> values; (2) the c> values of peptide intermediates are useful for judging solubility of peptide intermediates equal to or larger than an octapeptide level; (3) the Pro residue in a central position of a peptide chain is effective for increasing peptide solubility; and (4) there is critical chain length for peptide insolubility caused by a β-sheet aggregation.A strategy suitable for the design of the synthetic route or human proinsulin C-peptide is subsequently discussed on the basis of the solubility prediction of peptide intermediates.
- Narita Mitsuaki,Ogura, Toshihiko,Sato, Kazuhiro,Honda, Shinya
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p. 2433 - 2438
(2007/10/02)
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