- SIDE REACTIONS AND CADMIUM CATALYSED REMOVAL OF THE TRICHLOROETHOXYCARBONYL (TROC) PROTECTING GROUP.
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The Troc protecting group has been found to be unstable to the hydrogenolytic conditions used for removal of the benzyloxycarbonyl group; an improved method of removal employing cadmium dust in 50percent AcOH/DMF is described.
- Hancock, G.,Galpin, I. J.,Morgan, B. A.
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Read Online
- A kind of amino acid tanshinone phenolic derivative and its preparation method
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The invention relates to amino acid tanshinone phenolic ester derivatives and a preparation method thereof. The derivatives are obtained by reducing tanshinone compounds and performing esterified modification on the reduced tanshinone compounds and an amino acid into prodrugs, wherein the tanshinone compounds are phenanthrenequinone compounds which exist in salvia miltiorrhiza and have an o-quinone structure; the esterified amino acid is alpha-amino acid. The amino acid tanshinone phenolic ester derivatives are compounds having a structure of a general formula (I) or medicinal salts thereof, wherein R1 and R2 represent H or acyl alpha-amino acid and a salt thereof, and R1 and R2 are not H at the same time. The amino acid tanshinone phenolic ester derivatives have the beneficial effects that firstly, the new tanshinone derivatives are provided and the new substances have potential treatment effect on some serious diseases such as tumors, and secondly, amino acid tanshinone phenolic ester derivatives have excellent water solubility and thus can be prepared into injections conveniently in addition to various oral preparations, and therefore, the amino acid tanshinone phenolic ester derivatives are capable of quickly taking effect in disease treatment. As important prodrugs, the amino acid tanshinone phenolic ester derivatives have important application value.
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Paragraph 0105
(2016/10/09)
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- CHEMICAL CROSSLINKERS AND COMPOSITIONS THEREOF
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Chemical crosslinkers and methods of their synthesis are disclosed.
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Paragraph 0283; 0284
(2014/09/16)
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- Orthogonally protected artificial amino acid as tripod ligand for automated peptide synthesis and labeling with [99mTc(OH2) 3(CO)3]+
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1,2-Diamino-propionic acid (Dap) is a very strong chelator for the [ 99mTc(CO)3]+ core, yielding small and hydrophilic complexes. We prepared the lysine based Dap derivative l-Lys(Dap) in which the ε-NH2 group was replaced by the tripod through conjugation to its α-carbon. The synthetic strategy produced an orthogonally protected bifunctional chelator (BFC). The -NH2 group of the α-amino acid portion is Fmoc- and the -NH2 of Dap are Boc-protected. Fmoc-l-Lys(Dap(Boc)) was either conjugated to the N- and C-terminus of bombesin BBN(7-14) or integrated into the sequence using solid-phase peptide synthesis (SPPS). We also replaced the native lysine in a cyclic RGD peptide with l-Lys(Dap). For all peptides, quantitative labeling with the [99mTc(CO)3]+ core at a 10 μM concentration in PBS buffer (pH = 7.4) was achieved. For comparison, the rhenium homologues were prepared from [Re(OH2)3(CO) 3]+ and Lys(Dap)-BBN(7-14) or cyclo-(RGDyK(Dap)), respectively. Determination of integrin receptor binding showed low to medium nanomolar affinities for various receptor subtypes. The IC50 of cyclo-(RGDyK(Dap[Re(CO)3])) for αvβ3 is 7.1 nM as compared to 3.1 nM for nonligated RGD derivative. Biodistribution studies in M21 melanoma bearing nude mice showed reasonable α vβ3-integrin specific tumor uptake. Altogether, orthogonally protected l-Lys(Dap) represents a highly versatile building block for integration in any peptide sequence. Lys(Dap)-precursors allow high-yield 99mTc-labeling with [99mTc(OH2) 3(CO)3]+, forming small and hydrophilic complexes, which in turn leads to peptide radiopharmaceuticals with excellent in vivo characteristics.
- Shen, Yunjun,Schottelius, Margret,Zelenka, Karel,De Simone, Mariarosaria,Pohle, Karolin,Kessler, Horst,Wester, Hans-Jürgen,Schmutz, Paul,Alberto, Roger
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- Tandem catalysis for the preparation of cylindrical polypeptide brushes
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Here, we report a method for synthesis of cylindrical copolypeptide brushes via N-carboxyanhydride (NCA) polymerization utilizing a new tandem catalysis approach that allows preparation of brushes with controlled segment lengths in a straightforward, one-pot procedure requiring no intermediate isolation or purification steps. To obtain high-density brush copolypeptides, we used a "grafting from" approach where alloc-α-aminoamide groups were installed onto the side chains of NCAs to serve as masked initiators. These groups were inert during cobalt-initiated NCA polymerization and gave allyloxycarbonyl-α-aminoamide-substituted polypeptide main chains. The alloc-α-aminoamide groups were then activated in situ using nickel to generate initiators for growth of side-chain brush segments. This use of stepwise tandem cobalt and nickel catalysis was found to be an efficient method for preparation of high-chain-density, cylindrical copolypeptide brushes, where both the main chains and side chains can be prepared with controlled segment lengths.
- Rhodes, Allison J.,Deming, Timothy J.
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supporting information
p. 19463 - 19467
(2013/02/21)
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- THIAZOLIDINE DERIVATIVE AND MEDICINAL USE THEREOF
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A thiazolidine derivative represented by the formula (I) wherein each symbol is as defined in the specification, and a pharmaceutically acceptable salt thereof exhibit a potent DPP-IV inhibitory activity, and can be provided as an agent for the prophylaxis or treatment of diabetes, an agent for the prophylaxis or treatment of obesity and the like.
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- Stereocontrolled synthesis of onchidins
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(Chemical Equation Presented) The first total synthesis of a molecule possessing the stereochemistry proposed for onchidin is described. The structure synthesized appears to be different from that of the marine natural product.
- Peng, Yungui,Pang, Heung Wing,Ye, Tao
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p. 3781 - 3784
(2007/10/03)
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- Fairly marked enantioselectivity for the hydrolysis of amino acid esters by chemically modified enzymes
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The hydrolysis (deacylation) of enantiomeric substrates by the chemically modified enzymes decanoyl-α-chymotrypsin and decanoyl-trypsin was studied. Reaction activity for decanoyl-α-chymotrypsin was lower than that for the native enzyme, although intriguingly the enantioselectivity was markedly enhanced as compared with the native enzyme. In particular, the apparently complete enantioselective catalysis was attained for the hydrolytic cleavage of p-nitrophenyl N-dodecanoyl- D(L)-phenylalaninates. The enhancement of enantioselectivity, however, was not observed for decanoyl-trypsin. These results suggest that the chemically modified α-chymotrypsin by addition of hydrophobic groups has promoted enantioselectivity for the hydrolysis of hydrophobic esters.
- Yano, Yoshihiro,Shimada, Kenji,Okai, Jiro,Goto, Koichi,Matsumoto, Yoko,Ueoka, Ryuichi
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p. 1314 - 1318
(2007/10/03)
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- Synthesis of L-indospicine
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Preparation of L-indospicine in eight steps by a reaction sequence starting with L-lysine.
- Bence, Aimee K.,Crooks, Peter A.
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p. 2075 - 2082
(2007/10/03)
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- Fibrinolytic and antithrombotic protease from Spirodela polyrhiza.
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A fibrinolytic protease was purified from a Chinese herb (Spirodela polyrhiza). The protease has a molecular mass of 145 kDa and 70 kDa in gel filtration and SDS-polyacrlamide gel electrophoresis (PAGE), respectively, implying it is a dimer. Its optimum p
- Choi,Sa
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p. 781 - 786
(2007/10/03)
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- Purification and properties of fructosyl lysine oxidase from Fusarium oxysporum S-1F4.
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Fructosyl lysine oxidase (FLOD) was examined for its use in the enzymatic measurement of the level of glycated albumin in blood serum. To isolate microorganisms having such an enzyme activity, we used N epsilon-fructosyl N alpha-Z-lysine (epsilon-FL) as a sole nitrogen source in the enrichment culture medium. The isolated fungus, strain S-1F4, showed a high FLOD activity in the cell-free extract and was identified as Fusarium oxysporum. FLOD was purified to an apparent homogeneity on SDS-PAGE. The molecular mass of the subunit was 50 kDa on SDS-PAGE and seemed to exist in a monomeric form. The enzyme had an absorption spectrum characteristic of a flavoprotein and the flavin was found to be covalently bound to the enzyme. The enzyme acted against N epsilon-fructosyl N alpha-Z-lysine and N alpha-fructosyl N epsilon-Z-lysine and showed specificity for fructosyl lysine residues.
- Sakai,Yoshida,Isogai,Tani,Kato
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p. 487 - 491
(2007/10/02)
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- Enzymes in organic synthesis: Use of subtilisin and a highly stable mutant derived from multiple site-specific mutations
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A subtilisin mutant (subtilisin 8350) derived from subtilisin BPN' via six-specific mutations (Met50Phe, Gly169Ala, Asn76Asp, Gln206Cys, Tyr217Lys, and Asn218Ser) was found to be 100 times more stable than the wild-type enzyme in aqueous solution at room temperature and 50 times more stable than the wild type in anhydrous dimethylformamide. Kinetic studies using ester, thio ester, and amide substrates, and the transition-state analogue inhibitor Boc-Ala-Val-Phe-CF3, indicate the both the wild-type and the mutant enzymes have very similar specificities and catalytic properties. The inhibition constant (K(i)) = 5.0 μM) for the wild-type enzyme is approximately 5 times that of the mutant enzyme (K(i)) = 1.1 μM), suggesting that the mutant enzyme binds the reaction transition state more strongly than the wild-type enzyme. This result is consistent with the observed rate constants for the corresponding ester and amide substrates; i.e. the k(cat)/k(m) values for the mutant are larger than those for hhe wild-type enzyme. Application of the mutant enzyme and the wild-type enzyme to organic synthesis has been demonstrated in the regioselective acylation of nucleosides in anhydrous dimethylformamide (with 65-100% regioselectivity at the 5'-position), in the enantioselective hydrolysis of N-protected and unprotected common and uncommon amino acid esters in water (with 85-98% enantioselectivity for the L-isomer), and in the synthesis of di- and oligopeptides via aminolysis of N-protected amino acid and peptide esters. The enzymatic peptide synthesis was carried out under high concentrations of DMF (~50%) to improve substrate solubility and to minimize enzymatic peptide cleavage. Low enantioselectivity was observed in the enzymatic transformation of non-amino acid alcohols and acids.
- Wong,Chen,Hennen,Bibbs,Wang,L iu,Pantoliano,Whitlow,Bryan
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p. 945 - 953
(2007/10/02)
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- SYNTHESIS OF N-BENZYLOXYCARBONYL-L-α-AMINOADIPIC ACID, α-BENZYL ESTER
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A new synthesis of N-benzyloxycarbonyl-L-α-aminoadipic acid, α-benzyl ester (1) from L-lysine monohydrochloride (2) is reported.
- Baldwin, Jack E.,Killin, Stephen J.,Adlington, Robert M.,Spiegel, Udo
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p. 2633 - 2636
(2007/10/02)
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- Mild and Simple Biomimetic Conversion of Amines to Carbonyl Compounds
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4-Formyl-1-methylpyridinium benzenesulfonate is a convenient reagent for the chemical modification of primary amines to aldehydes and ketones.This method mimics the biological process for transamination reactions with pyridoxal (vitamin b6).As in that process, it involves imine formation, prototropic rearrangement, and hydrolysis.The conditions are extremely mild and are compatible with a large variety of sensitive functional groups.This process provides a simple and a efficient alternative to the somewhat harsher procedures generally employed for such transformations.
- Buckley, Thomas F.,Rapoport, Henry
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p. 4446 - 4450
(2007/10/02)
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- INTRAMOLECULAR CATALYTIC MECHANISMS INVOLVED IN THE ALKALINE HYDROLYSIS OF p-NITROPHENYL ESTERS OF α-CARBOBENZOXY AMINO ACIDS
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A study on the alkaline hydrolysis of p-nitrophenyl esters of α-carbobenzoxy amino acids, in the presence and absence of free amino acids as catalysts, are reported.The effect of free amino acids represents an interesting model for the study of the cataly
- Ascenzi, Paolo,Sleiter, Giancarlo,Antonini, Eraldo
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p. 307 - 318
(2007/10/02)
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