- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
-
Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
- Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
-
supporting information
p. 8297 - 8302
(2021/03/01)
-
- Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
-
Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
- Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
-
p. 1080 - 1090
(2020/05/25)
-
- Determination of Chemical and Enantiomeric Purity of α-Amino Acids and their Methyl Esters as N-Fluorenylmethoxycarbonyl Derivatives Using Amylose-derived Chiral Stationary Phases
-
Liquid chromatographic enantiomer separation and simultaneous determination of chemical and enantiomeric purity of α-amino acids and their methyl esters as N-fluorenylmethoxycarbonyl (FMOC) derivatives was performed on three covalently bonded type chiral stationary phases (CSPs) derived from amylose derivatives. The enantiomer separation of α-amino acid esters as N-FMOC derivatives was better than that of the corresponding acids, especially for CSP 1 and 2. Chemical impurities as the corresponding racemic acids present in several commercially available racemic amino acid methyl esters were observed to be 0.49–17.50%. Enantiomeric impurities of several commercially available L-amino acid methyl esters were found to be 0.03–0.58%, whereas chemical impurities as the corresponding racemic acids present in the same analytes were found to be 0.13–13.62%. This developed analytical method will be useful for the determination of chemical and enantiomeric purity of α-amino acids and/or esters as N-FMOC derivatives using amylose-derived CSPs.
- Islam, Md. Fokhrul,Adhikari, Suraj,Paik, Man-Jeong,Lee, Wonjae
-
p. 332 - 338
(2019/04/13)
-
- Unwanted hydrolysis or α/β-peptide bond formation: How long should the rate-limiting coupling step take?
-
Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
- Goldschmidt G?z, Viktória,Nagy, Adrienn,Farkas, Viktor,Keszei, Ern?,Perczel, András
-
p. 30720 - 30728
(2019/10/28)
-
- Structure-guided engineering of: Meso -diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
-
meso-Diaminopimelate dehydrogenase (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding d-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a Symbiobacterium thermophilum DAPDH (StDAPDH) gave rise to a double-site mutant W121L/H227I, which showed dramatically improved enzyme activities towards various 2-keto acids including these sterically bulky substrates. Several d-amino acids were prepared in optically pure form. The molecular docking of substrates into the active sites of wild-type and mutant W121L/H227I enzymes revealed that the substrate binding cavity of the mutant enzyme was reshaped to accommodate these bulky substrates, thus leading to higher enzyme activity. These results lay a foundation for further shaping the substrate binding pocket and manipulating the interactions between the substrate and binding sites to access highly active d-amino acid dehydrogenases for the preparation of synthetically challenging d-amino acids.
- Cheng, Xinkuan,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
-
p. 4994 - 5002
(2018/10/17)
-
- Desyl and phenacyl as versatile, photocatalytically cleavable protecting groups: A classic approach in a different (visible) light
-
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
-
p. 6821 - 6826
(2017/11/06)
-
- ALDEHYDE CAPTURE LIGATION TECHNOLOGY FOR SYNTHESIS OF AMIDE BONDS
-
The present invention relates to ligation agents and their use in making an amide ligation product. Methods of making the ligation agents are also disclosed.
- -
-
Paragraph 0125
(2017/09/13)
-
- Visible-light photoredox-catalyzed desulfurization of thiol- and disulfide-containing amino acids and small peptides
-
A scalable protocol for the desulfurization of cysteine by using visible light, the photocatalyst Ir(dF(CF3)ppy)2(dtb-bpy)PF6 and triethylphosphite under biphasic reaction conditions has been developed. The loading of the catalyst can be as low as 0.01?mol%, which can be efficiently removed during the workup (≤0.3?ppm), giving rise to the corresponding desulfurized product in high yields. This method has been applied also to cystine, penicillamine, and reduced and oxidized glutathione. The desulfurization has been found to be pH sensitive, with an optimal pH value of 6.5 and 7.0 for the cysteine derivatives and glutathione, respectively. In addition, during the desulfurization of a decapeptide containing cysteine and methionine, concurrent oxidation of the two sulfur-containing residues to disulfide and sulfoxide has been observed. Therefore, whereas the presented protocol allows a straightforward visible light-mediated desulfurization of simple thiols by using very low catalyst loading and a cost-effective trialkylphosphite as thiyl radical trapping agent, its application to complex substrates needs to be carefully validated. Copyright
- Lee, Myungmo,Neukirchen, Saskia,Cabrele, Chiara,Reiser, Oliver
-
p. 556 - 562
(2017/08/14)
-
- Fmoc-OPhth, the reagent of Fmoc protection
-
Fmoc-OSu has been widely used for Fmoc protection of amino groups, especially amino acids, in solid phase peptide synthesis. However, it has been recognized that Fmoc-βAla-OH is formed as a by-product via the Lossen rearrangement during the reaction. Since we reconfirmed the formation of Fmoc-βAla-OH during the preparation of Fmoc-AA-OH by Fmoc-OSu, Fmoc-OPhth was designed and synthesized as a new Fmoc reagent to avoid the formation of Fmoc-βAla-OH. Furthermore, Fmoc protection by Fmoc-OPhth and Fmoc-SPPS were evaluated. The various Fmoc-amino acids prepared by Fmoc-OPhth were carried out in good yields and these are applicable in Fmoc-SPPS.
- Yoshino, Ryo,Tokairin, Yoshinori,Kikuchi, Mari,Konno, Hiroyuki
-
supporting information
p. 1600 - 1603
(2017/04/03)
-
- Synthesis and biological evaluation of novel FK228 analogues as potential isoform selective HDAC inhibitors
-
Novel C4- and C7-modified FK228 analogues were efficiently synthesized in a highly convergent and unified manner. This synthesis features the amide condensation of glycine-d-cysteine-containing segments with d-valine-containing segments for the direct assembly of the corresponding seco-acids, which are key precursors of macrolactones. The HDAC inhibition assay and cell-growth inhibition analysis of the synthesized analogues revealed novel aspects of their structure-activity relationship. This study demonstrated that simple modification at the C4 and C7 side chains in FK228 is effective for improving both HDAC inhibitory activity and isoform selectivity; moreover, potent and highly isoform-selective class I HDAC1 inhibitors were identified.
- Narita, Koichi,Matsuhara, Keisuke,Itoh, Jun,Akiyama, Yui,Dan, Singo,Yamori, Takao,Ito, Akihiro,Yoshida, Minoru,Katoh, Tadashi
-
p. 592 - 609
(2016/07/06)
-
- A kind of amino acid tanshinone phenolic derivative and its preparation method
-
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.
- -
-
Paragraph 0055
(2016/10/09)
-
- Site-selective chemical cleavage of peptide bonds
-
Site-selective cleavage of extremely unreactive peptide bonds is a very important chemical modification that provides invaluable information regarding protein sequence, and it acts as a modulator of protein structure and function for therapeutic applications. For controlled and selective cleavage, a daunting task, chemical reagents must selectively recognize or bind to one or more amino acid residues in the peptide chain and selectively cleave a peptide bond. Building on this principle, we have developed an approach that utilizes a chemical reagent to selectively modify the serine residue in a peptide chain and leads to the cleavage of a peptide backbone at the N-terminus of the serine residue. After cleavage, modified residues can be converted back to the original fragments. This method exhibits broad substrate scope and selectively cleaves various bioactive peptides with post-translational modifications (e.g. N-acetylation and -methylation) and mutations (d- and β-amino acids), which are a known cause of age related diseases.
- Elashal, Hader E.,Raj, Monika
-
supporting information
p. 6304 - 6307
(2016/05/24)
-
- HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
-
Provided herein are novel heteroaromatic derivatives, or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a prodrug, a pharmaceutically acceptable salt or a prodrug thereof, and pharmaceutical compositions containing such compounds. Also provided herein are uses of such compounds or pharmaceutical compositions thereof in the manufacture of a medicament for treating respiratory diseases, especially chronic obstructive pulmonary disease (COPD).
- -
-
Paragraph 00730
(2015/11/10)
-
- Aqueous MW eco-friendly protocol for amino group protection
-
In this paper a new catalyst-free and on-water method for protection of amines and amino acids with di-tert-butyl dicarbonate, 9-fluorenylmethoxycarbonyl chloride, acetyl chloride and tosyl chloride is presented. The protection can be realized in a few minutes under microwave-assistance. The reaction proved to be chemoselective in presence of ambident nucleophiles and water solution of di-tert-butyl carboxylic acid or chloride acid are the only wastes produced.
- Nardi,Cano, N. Herrera,Costanzo,Oliverio,Sindona,Procopio
-
p. 18751 - 18760
(2015/06/15)
-
- Structure Revision of Similanamide to PF1171C by Total Synthesis
-
The total synthesis of the proposed structure of similanamide, a cyclic hexapeptide recently isolated from the marine sponge-associated fungus Aspergillus similanensis KUFA 0013, was achieved by solid-phase synthesis of a linear precursor and solution-phase macrolactamization. The NMR spectra of our synthetic final product were not identical to those of the isolated material and led us to conclude that similanamide is identical to PF1171C, a previously reported diastereomeric hexapeptide.
- Masuda, Yuichi,Tanaka, Ren,Ganesan,Doi, Takayuki
-
p. 2286 - 2291
(2015/10/12)
-
- Efficient and practical procedure for the esterification of the free α-carboxylic acid of amino acid residues with β-(trimethylsilyl)ethoxymethyl chloride and triisopropylsilyl chloride
-
An efficient and practical procedure for the free α-carboxylic acid esterification of amino acid residues with β-(trimethylsilyl)ethoxymethyl chloride and triisopropylsilyl chloride is described. The reaction takes place under mild conditions and the expected protected amino acids are obtained in good to excellent yields. Our method provides a useful alternative for the C-terminal carboxylic acid protection of amino acids and peptides. Moreover, the removal of such protection was also achieved under mild conditions, without affecting either the other protecting groups at the α-amino moiety and side chains or the optical integrity at the α-position of the amino acid residues. Examples of their use in peptide synthesis are also illustrated.
- Suppo, Jean-Simon,De Sant'Ana, Danilo Pereira,Dias, Luiz Carlos,De Figueiredo, Renata Marcia,Campagne, Jean-Marc
-
p. 3075 - 3084
(2015/01/08)
-
- Heating and microwave assisted SPPS of C-terminal acid peptides on trityl resin: The truth behind the yield
-
Despite correct purity of crude peptides prepared on trityl resin by Fmoc/tBu microwave assisted solid phase peptide synthesis, surprisingly, lower yields than those expected were obtained while preparing C-terminal acid peptides. This could be explained
- Echalier, Cecile,Al-Halifa, Soultan,Kreiter, Aude,Enjalbal, Christine,Sanchez, Pierre,Ronga, Luisa,Puget, Karine,Verdie, Pascal,Amblard, Muriel,Martinez, Jean,Subra, Gilles
-
p. 1395 - 1403
(2014/01/06)
-
- A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
-
The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.
- Siciliano, Carlo,De Marco, Rosaria,Guidi, Ludovica Evelin,Spinella, Mariagiovanna,Liguori, Angelo
-
p. 10575 - 10582
(2013/02/22)
-
- Cyanoacetamide-based oxime carbonates: An efficient, simple alternative for the introduction of Fmoc with minimal dipeptide formation
-
Nowadays, most peptides are chemically achieved by using the Fmoc/tBu protection strategy, due to its fully orthogonal character, mild temporary group removal and resin cleavage steps. However, its introduction into N-unprotected amino acids is not exempt of synthetic inconveniences, such as dipeptide formation. Lately, novel oxime carbonates were introduced in the arsenal of reagents for the introduction of Fmoc, presenting almost negligible percentage of side-products. Herein, an enforced version of this family of Fmoc-carbonates is presented, containing stable and highly acidic cyanoacetamide-based oximes as leaving group. Such reactive species, affordable in only two steps from simple, readily available starting materials, show unusual ability to obtain the corresponding Fmoc-protected residues in high yield and minimal impact of detrimental side-products, mainly Fmoc-dipeptides.
- Khattab, Sherine N.,Subirós-Funosas, Ramon,El-Faham, Ayman,Albericio, Fernando
-
experimental part
p. 3056 - 3062
(2012/06/01)
-
- An efficient and expeditious Fmoc protection of amines and amino acids in aqueous media
-
A new and environmentally friendly Fmoc protection of a variety of aliphatic and aromatic amines, amino acids, amino alcohols and amino phenols is reported in aqueous media under mild and catalyst-free conditions. The reaction proved to be chemoselective in presence of ambident nucleophiles.
- Gawande, Manoj B.,Branco, Paula S.
-
supporting information; experimental part
p. 3355 - 3359
(2012/01/06)
-
- Liquid-chromatography quantitative analysis of 20 amino acids after derivatization with FMOC-CI and its application to different origin Radix isatidis
-
We developed a simple, rapid and reliable method for determination of 20 common amino acids based on derivatization with 9-fluorenylmethyl chloroformate (FMOC-CI) and RP-LC/UV, this method was first introduced into quantitative analysis of amino acids. The amino groups of amino acids were trapped with FMOC-CI to form amino acid-FMOC-Cl adducts which can be suitable for LC-UV. Chromatographic separation was performed on a C18 column with a mobile phase gradient consisting of acetonitrile and sodium acetate solution. This method was shown to be sensitive for 20 common amino acids. In the intra-day precisions assay, the range of RSDs was 3.21-7.67% with accuracies of 92.34-102.51%; for the inter-day precisions assay, the range of RSDs was 5.82-9.19% with accuracies of 90.25-100.63%. The results also indicated that solutions of amino acids-FMOC-Cl can be kept at room temperature for at least 24 h without showing significant losses in the quantified values. The validated method was successfully applied to the determination of major four kinds of amino acids in R. isatidis samples (Arg, Pro, Met and Val). The total content of amino acids in different origin R. isatidis was 13.32-19.16 mg/g. The differences between R. isatidis samples were large using HCA.
- Zhou, Wei,Zhang, Xiao-Yan,Duan, Geng-Li
-
experimental part
p. 509 - 515
(2012/01/04)
-
- Derivates of Polyethylene Glycol Modified Thymosin Alpha 1
-
Pharmaceutical compositions that include thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol, and their pharmaceutical acceptable salts, are generally disclosed. Also, new methods used to prepare these thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol are generally provided. The presently disclosed compounds and their salts can be prepared administered to humans to treat immune disease and can also be used in adjuvant treatment.
- -
-
-
- Basic techniques of working on a solid phase: From ABC of the peptide synthesis to libraries of non-natural amino acids
-
Libraries of hardly available amino acids bearing a heteroaromatic ring (2-pyrimidyl, substituted 2-pyridyl or 2-thiazolyl) at the amino group were prepared using solid-phase synthesis on various resins. The synthesized compounds are structurally similar to some known antidiabetic drugs. The paper combines features of a review (elementary introduction to the solid-phase synthesis methodology and technique for beginners and selected methods from peptide chemistry) and step-by-step experimental protocols (tested by the authors) useful as a methodic tool. The presented protocols (immobilization and modification of amino acids, placing and removal of common protective groups) require no sophisticated equipment and may be useful as pictorial introductory tasks for students education. Pleiades Publishing, Ltd., 2010.
- Babaev,Ermolat'ev
-
experimental part
p. 2572 - 2589
(2011/04/15)
-
- FLUORENE COMPOUND
-
Particular compounds having a fluorene skeleton are superior in broad utility and stability, as a protecting reagent for liquid phase synthesis of amino acids and/or peptides.
- -
-
-
- Reversible hydrogen transfer between cysteine thiyl radical and glycine and alanine in model peptides: Covalent H/D exchange, radical-radical reactions, and l - To D -Ala conversion
-
The reversible intramolecular hydrogen transfer reaction of peptide Cys thiyl radicals with Gly and Ala residues was studied in model peptides, where thiyl radicals were either generated through photochemical cleavage of disulfide bonds or through the rea
- Mozziconacci, Olivier,Kerwin, Bruce A.,Sch?neich, Christian
-
experimental part
p. 6751 - 6762
(2011/01/03)
-
- (2,6-Dichloro-4-alkoxyphenyl)-(2,4-dichlorophenyl)methyl trichloroacetimidates: Protection of alcohols and carboxylic acids in solution or on polymer support
-
(2,6-Dichloro-4-methoxyphenyl)-(2,4-dichlorophenyl)-methyl trichloroacetimidate can be efficiently activated by TMSOTf (10-100 mol%) to react with alcohols and carboxylic acids. Under these conditions a wide variety of alcohols can be transformed into the corresponding ethers in excellent yields with a slight excess of the trichloroacetimidate. The resulting ethers are not susceptible to typical deprotection conditions for benzyl and 4-methoxybenzyl ether groups, however, they can be conveniently deprotected by treatment with 30-50% trifluoroacetic acid in dichloromethane. Polymer-bound (2,6-dichloro-4-alkoxyphenyl)-(2,4-dichlorophenyl)methyl trichloroacetimidate is useful for immobilization of alcohols and carboxylic acids.
- Kurosu, Michio,Li, Kai
-
experimental part
p. 3633 - 3641
(2010/03/05)
-
- Total synthesis of (+)-azinothricin and (+)-kettapeptin
-
(Chemical Equation Presented) Asymmetric total syntheses of (+)-azinothricin and (+)-kettapeptin have been completed through a common new pathway that exploits a highly chemoselective coupling reaction between the fully elaborated cyclodepsipeptide 5 and the glycal activated esters 3 and 4 at the final stages of both respective syntheses.
- Hale, Karl J.,Manaviazar, Soraya,George, Jonathan H.,Walters, Marcus A.,Dalby, Stephen M.
-
supporting information; experimental part
p. 733 - 736
(2009/09/30)
-
- Efficient procedure for the preparation of oligomer-free N-fmoc amino acids
-
A two-step method is presented for the peptide-free, high-purity, and high-yield synthesis of N-Fmoc amino acids. The first step involves the preparation of stable dicyclohexylammonium-amino acid ionic adduct in acetone. Subsequently, the ionic adducts, on reaction with Fmoc-Nosu under mild alkaline conditions, give dipeptide-free N-Fmoc amino acids. The positive charge of the dicyclohexylammonium counterion in the ionic salt has a longer radius, moderating the nucleophilicity of the carboxylate ion of the amino acid and preventing by-products by arresting the formation of mixed anhydrides, the precursors of oligopeptide impurities.
- Nowshuddin, Shaik,Rao,Reddy, A. Ram
-
experimental part
p. 2022 - 2031
(2009/11/30)
-
- Fluorogenic ester substrates to assess proteolytic activity
-
The synthesis of a new type of fluorogenic ester substrates is described. Prepared from fluorescein in three steps with common commercially available precursors, they all generate bright green fluorescence upon proteolysis. Their particular structure allows the same substrate be used to report enzymatic activity of various proteases from serine and cysteine superfamilies. The substrate cleavage is sensitive to specific protease inhibitors providing a tool for inhibitor screening.
- Mugherli, Laurent,Burchak, Olga N.,Chatelain, Francois,Balakirev, Maxim Y.
-
p. 4488 - 4491
(2007/10/03)
-
- PHOSPHONIUM SALTS DERIVATIVES AND THEIR USE AS SOLUBILITY CONTROLLING AUXILIARIES
-
The present invention relates to the use of compounds of formula (IA) or (IIA): insert formula (IA) and (IIA) from page 15 of the disclosure wherein A represents various substituted or unsubstituted groups such as furyl, phenyl, pyridyl, naphthyl, or thiophenyl; X- represents an anion; and L1 represents a linker, as solubility controlling auxiliaries. These compounds can also be used as solubility controlling fragments of a molecule. The invention also relates to various methods of controlling the solubility of a molecule or a substrate. Moreover, the invention also relates to various phosphonium supported reagents or various phosphonium salts derivatives.
- -
-
Page/Page column 52
(2010/02/14)
-
- Enzyme-cleavable linkers for peptide and glycopeptide synthesis
-
Hydroxymethylphenoxy linkers that are commonly used in solid phase peptide synthesis are surprisingly susceptible to efficient cleavage by the protease chymotrypsin with a broad range of amino acid residues being tolerated at the scissile bond; this enzyme-cleavable linker system has been applied to peptide and glycopeptide synthesis. The Royal Society of Chemistry 2005.
- Maltman, Beatrice A.,Bejugam, Mallesham,Flitsch, Sabine L.
-
p. 2505 - 2507
(2007/10/03)
-
- A novel and efficient method for cleavage of phenacylesters by magnesium reduction with acetic acid
-
(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
-
p. 1723 - 1724
(2007/10/03)
-
- A mild and selective method for the hydrolysis of esters with trimethyltin hydroxide
-
Mild, selective, and efficient: A new method that involves the use of trimethyltin hydroxide for the hydrolysis of specific ester groups allows chemists to steer clear of unwanted elimination reactions and epimerizations. For example, the conversion of ester 1 into carboxylic acid 2 takes place under mild conditions, with nearly complete retention of stereochemical integrity. 1,2-DCE = 1,2-dichloroethane.
- Nicolaou,Estrada, Anthony A.,Zak, Mark,Lee, Sang Hyup,Safina, Brian S.
-
p. 1378 - 1382
(2007/10/03)
-
- GLP-2 compounds, formulations, and uses thereof
-
The present invention relates to novel human glucagon-like peptide-2 (GLP-2) peptides and human glucagon-like peptide-2 derivatives which have a protracted profile of action as well as polynucleotide constructs encoding such peptides, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.
- -
-
-
- One-pot preparation of N-carbamate protected amino acids via the azide
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A convenient and efficient method for the preparation of fluorenylmethyloxycarbonyl (Fmoc) and allyloxycarbonyl (Alloc) amino acids is proposed. This method is particularly attractive due to the fact that the reaction sequence Fmoc/Alloc-chloride to Fmoc/Alloc-azide to Fmoc/Alloc-amino acid can readily be carried out in one pot. A further advantage is the minimization of byproducts, which are easily removed during the workup. Most important, this strategy minimizes the formation of dipeptides that are difficult to remove by crystallization. Thus, Fmoc and Alloc amino acids are obtained in high yield (60-90%) and purity as evidenced by thin-layer chromatography, reversed-phase high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance.
- Cruz, Luis J.,Beteta, Natalia G.,Ewenson, Ariel,Albericio, Fernando
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p. 920 - 924
(2013/09/03)
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- A novel protecting group for constructing combinatorial peptide libraries
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3,4,5-Tris(octadecyloxy)benzyl alcohol, HO-Bzl(OC18)3, was prepared from gallic acid and stearyl bromide. Using conventional step-wise elongation, N,C-protected peptides, Fmoc - AAn - ... - AA1 - OBzl(OC18)3, were synthesized. The substituted benzyl esters were selectively cleaved by a treatment with 4 M hydrogen chloride in ethyl acetate to give Fmoc - AAn - ... - AA1 - OH and HO - Bzl(OC18)3. Thus, the substituted benzyl group is effective for the protection of C-terminal carboxyl groups in liquid-phase peptide synthesis. Because the substituted benzyl group has a moderately high molecular weight, Fmoc - AAn - ... - AA1 - OBzl(OC18)3 can be easily purified by size-exclusion chromatography; all protected peptides are eluted in the void fraction of a Sephadex LH-20 gel-filtration column. The combination of the carboxyl-protecting group Bzl(OC18)3 with simple purification by the gel-filtration gives a novel route for constructing combinatorial peptide libraries in the solution phase.
- Tamiaki, Hitoshi,Obata, Tomoyuki,Azefu, Yasuo,Toma, Kazunori
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p. 733 - 738
(2007/10/03)
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- A new polymer-supported reagent for the Fmoc-protection of amino acids
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A new polymer-supported Fmoc-OSu (Fmoc-P-OSu) has been prepared from polymer-bound N-hydroxysuccinimide (P-HOSu), and used as a solid-supported reagent for the Fmoc-protection of amino groups. The residual P-HOSu generated after the protection reaction can be separated by simple filtration and reused.
- Chinchilla, Rafael,Dodsworth, David,Nájera, Carmen,Soriano, José
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p. 7579 - 7581
(2007/10/03)
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- Selective deprotection of phenacyl, benzyl and methyl esters of N-protected amino acids and dipeptides and N-protected amino acids benzyl ester linked to resins with bis(tributyltin) oxide
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Phenacyl, methyl and benzyl esters of various N-α-Boc, N-α-Cbz or N,N-dimethylamino protected amino acids and dipeptides, as well as esters of N-α-protected amino acids linked to Wang and Pam resins have been efficiently and chemoselectively cleaved by bis(tributyltin) oxide in aprotic solvents to give the corresponding carboxylic acids in good yields. Moreover, the absence of racemization during the deprotection has been demonstrated. A limitation of the method is the instability of the N-ε-Fmoc group in the amino acid esters 8 and 10, N-α-Fmoc-L-alanine linked to Wang resin 23 and the Cbz protecting groups in N-α-Boc-N-ε-Cbz-L-lysine benzyl and methyl esters (5 and 7), respectively, and N-α-Cbz-L-alanyl-L-alanine methyl ester 19. In the case of N-α-protected dipeptides, there was no evidence of free amino acid which indicates that the peptide bond is unaffected.
- Salomon, Claudio J.,Mata, Ernesto G.,Mascaretti, Oreste A.
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p. 995 - 999
(2007/10/03)
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- Non-destructive Cleavage of N-Acylsultams Under Neutral Conditions: Preparation of Enantiomerically, Pure Fmoc-Protected α-Amino Acids
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Heating diastereoisomerically pure N-acylsultams 3 or 4 with allyl alcohol/Ti(OR)4 efficiently yields sultams 1 or 2 and allyl esters 5.Esters 5 are hydrolyzed under nonbasic conditions in the presence of Wilkinson's catalyst to give enantiomerically and diastereoisomerically pure carboxylic acids 7.A series of carbonyl-(Fmoc)-protected amino acids 14 were thus prepared from N-acylsultams 12.
- Oppolzer, Wolfgang,Lienard, Philippe
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p. 2572 - 2582
(2007/10/02)
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- A New Synthesis of Thymosin α1
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Thymosin α1, an N-acetylated octacosa thymus peptide, isolated first from thymosin fraction 5, is synthesized by the solid phase method using the p-benzyloxybenzyl alcohol/polystyrene/divinylbenzene resin, Nα-Fmoc-amino acids and those with tert-butyl or Boc side chain protection.All couplings are performed with the Bop reagent.The peptide is purified by a combination of gel chromatography and preparative HPLC, its purity checked by amino acid analysis and analytical HPLC, and the biological activity tested by the E-rosette assay.
- Echner, Hartmut,Voelter, Wolfgang
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p. 1095 - 1098
(2007/10/02)
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- 5-Norbornene-2,3-dicarboximido Carbonochloridate. A New Stable Reagent for the Introduction of Amino-Protecting Groups
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The synthesis of activated carbonates, based on a new carbonochloridate derived from N-hydroxy-5-norbornene-2,3-dicarboximide, is reported.These activated carbonic esters are excellent reagents for the introduction of all currently used urethane protecting groups.
- Henklein, Peter,Heyne, Hans-Ulrich,Halatsch, Wolf-Rainer,Niedrich, Hartmut
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p. 166 - 167
(2007/10/02)
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- 9-Fluorenylmethyl Pentafluorophenyl Carbonate as a Useful Reagent for the Preparation of N-9-Fluorenylmethyloxycarbonylamino Acids and their Pentafluorophenyl Esters
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9-Fluorenylmethyl pentafluorophenyl carbonate is a useful reagent for the efficient, side reaction-free introduction of N-9-fluorenylmethyloxycarbonyl protecting group into amino acids and for the subsequent preparation of their pentafluorophenyl esters.Some new compounds of both types are described.
- Schoen, Istvan,Kisfaludy, Lajos
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p. 303 - 305
(2007/10/02)
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- Solid phase synthesis without repetitive acidolysis. Preparation of leucyl-alanyl-glycyl-valine using 9-fluorenylmethyloxycarbonylamino acids.
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The utility of repetitive nonhydrolytic base cleavage of alpha-amino protective groups in solid phase peptide synthesis is shown by a preparation of the model tetrapeptide leucyl-alanyl-glycyl-valine on a p-benzyloxybenzyl ester polystyrene--1% divinylbenzene resin support. Nalpha-9-Fluorenylmethyloxycarbonyl (Fmoc: Carpino & Han, 1970, 1972) amino acids were coupled by the symmetrical anhydride procedure, followed by Fmoc group cleavage using 50% piperidine in methylene chloride. Quantitative removal of the Fmoc-tetrapeptide from the solid support was effected by treatment with 55% trifluoroacetic acid in methylene chloride. Homogeneous free tetrapeptide was obtained in 87% overall yield. The procedure is proposed to offer advantages over present solid phase methods which use acidolysis for repetitive alpha-amino group deblocking.
- Meienhofer,Waki,Heimer,Lambros,Makofske,Chang
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p. 35 - 42,37,39
(2007/10/06)
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- Solid phase synthesis with base N alpha-protecting group cleavage
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An improved solid phase peptide synthesis method is disclosed utilizing base labile Nα-amino acid protecting groups. Such method provides a more efficient synthesis procedure in that it eliminates acid treatment thereby preventing loss of peptide from the support during each deprotection cycle and eliminates a substantial number of wash cycles in each step. A preferred base labile Nα-amino protecting group is the 9-fluorenylmethyloxycarbonyl group (Fmoc) and a preferred base for deprotection is piperidine.
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