- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
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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.
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supporting information
p. 8297 - 8302
(2021/03/01)
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- Method for preparing Fmoc-Tyr (tBu)-OH
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The invention relates to a method for preparing FmocTyr (tBu)-OH, and belongs to the technical field of medical intermediate chemical engineering. The technical problem to be solved by the invention is to provide a method for preparing Fmoc-Tyr (tBu)-OH with good safety. The method comprises the following steps: a, mixing an Fmoc-Tyr-OR solid, tert-butyl acetate, perchloric acid and tert-butyl alcohol to react, adjusting the pH value to 5-6, separating out a solid, filtering, washing and drying to obtain an Fmoc-Tyr (tBu)-OR solid, wherein R is a C1-C4 alkyl; and b, carrying out hydrolysis onthe Fmoc-Tyr (tBu)-OR solid to obtain an Fmoc-Tyr (tBu)-OH product. The method is improved on the basis of the existing synthetic route, isobutene is not added when tert-butyl is introduced, the operation is simple and controllable, the safety is good, the cost is low, the production steps can be effectively shortened, the production efficiency and the yield are improved, and the method is suitable for modern industrial production.
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- Supported Catalytically Active Supramolecular Hydrogels for Continuous Flow Chemistry
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Inspired by biology, one current goal in supramolecular chemistry is to control the emergence of new functionalities arising from the self-assembly of molecules. In particular, some peptides can self-assemble and generate exceptionally catalytically active fibrous networks able to underpin hydrogels. Unfortunately, the mechanical fragility of these materials is incompatible with process developments, relaying this exciting field to academic curiosity. Here, we show that this drawback can be circumvented by enzyme-assisted self-assembly of peptides initiated at the walls of a supporting porous material. We applied this strategy to grow an esterase-like catalytically active supramolecular hydrogel (CASH) in an open-cell polymer foam, filling the whole interior space. Our supported CASH material is highly efficient towards inactivated esters and enables the kinetic resolution of racemates. This hybrid material is robust enough to be used in continuous flow reactors, and is reusable and stable over months.
- Rodon Fores, Jennifer,Criado-Gonzalez, Miryam,Chaumont, Alain,Carvalho, Alain,Blanck, Christian,Schmutz, Marc,Serra, Christophe A.,Boulmedais,Schaaf, Pierre,Jierry, Lo?c
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supporting information
p. 18817 - 18822
(2019/11/16)
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- A N-(9-fluorenylmethyloxycarbonyl)-O-tert-butyl-L-tyrosine method for the preparation of
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The invention relates to a method for preparing N-(9-fluorenylmethoxy carbony)-O-tertiary butyl-L-tyrosine. The problem that an enantiomer is easily generated is solved. The method comprises the following synthetic steps: (1) dissolving L-Tyr into a methanol solution, adding SOCl2 and then carrying out reflux reaction, so as to obtain Tyr-OMe.HCl; (2) dissolving the Tyr-OMe.HCl into a water solution, adding AcOEt and Na2CO3 and then reacting with Z-Cl, and controlling the pH of the system at 7-10, so as to obtain Z-L-Tyr-OMe; (3) dissolving the Z-L-Tyr-OMe into a CH2Cl2 solution, adding H2SO4 and isobutene, reacting at normal temperature for 1-10 days, so as to obtain Z-L-Tyr(tBu)-OMe; (4) adding the NaOH solution to the Z-L-Tyr(tBu)-OMe to react, so as to obtain Z-L-Tyr(tBu); (5) dissolving the Z-L-Tyr(tBu) into methanol, adding Pd/C, and leading in hydrogen to react, so as to obtain L-Tyr(tBu); (6) dissolving Z-L-Tyr(tBu) into the water solution, adding the Na2CO3 and THF and then reacting with Fmoc-osu, and controlling the pH of the system at 8-10, so as to obtain Fmoc-Tyr(tBu). By adopting the method, generation of the enantiomer is avoided, and the citric acid is taken as an acidifier, so that the product is more stable, and the reaction processes do not relate to high-temperature and high-pressure reaction, and the method is applicable to large-scale production.
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- A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids
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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
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p. 10575 - 10582
(2013/02/22)
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- Efficient procedure for the preparation of oligomer-free N-fmoc amino acids
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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
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experimental part
p. 2022 - 2031
(2009/11/30)
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- Stereoretentive synthesis and chemoselective amide-forming ligations of C-terminal peptide α-ketoacids
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C-Terminal peptide cyanosulfur ylides are readily converted to C-terminal peptide α-ketoacids, poised for chemoselective amide-forming reactions with hydroxylamines. These easily prepared and bench stable ylides are quickly and selectively oxidized with a
- Ju, Lei,Lippert, Alexander R.,Bode, Jeffrey W.
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p. 4253 - 4255
(2008/12/20)
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- A convenient, general synthesis of 1,1-dimethylallyl esters as protecting groups for carboxylic acids
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(Chemical Equation Presented) Carboxylic acids were converted in high yield to their 1,1-dimethylallyl (DMA) esters in two steps. Palladium-catalyzed deprotection of DMA esters was shown to be compatible with tert-butyl, benzyl, and Fmoc protecting groups, and Fmoc deprotection could be carried out selectively in the presence of DMA esters. DMA esters were also shown to be resistant to nucleophilic attack, suggesting that they will serve as alternatives to tert-butyl esters when acidic deprotection conditions need to be avoided.
- Sedighi, Minoo,Lipton, Mark A.
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p. 1473 - 1475
(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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- Photogenerated reagents
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This invention describes reagent precursors and methods for chemical and biochemical reactions. These reagent precursors that can be activated in solution upon irradiation to generate reagents required for the subsequent chemical reactions. Specifically, photogenerated reagents (PGR) are useful for controlling parallel combinatorial synthesis and various chemical and biochemical reactions.
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Page/Page column 20-21
(2008/06/13)
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- Angiopeptin cyclopeptide compounds
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The invention relates to a compound selected from those of formula (I) (SEQ ID NO:1): STR1 in which R1, R2, X1 and X2 are as defined in the description, useful as inhibitor of the proliferation component of vascular smooth muscle cells.
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- Application of t-Butyldimethylsilyl Ethers of Serine, Threonine and Tyrosine in Peptide Synthesis
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The utility of Tbdms (t-butyldimethylsilyl) ethers, prepared conveniently in a one pot procedure from Nα-Fmoc (9-fluorenylmethoxycarbonyl) and Nα-Z (benzyloxycarbonyl) hydroxyamino acids, is demonstrated: peptide bond formation and esterification to 4-alkoxybenzylalcohol resin are achieved readily with these derivatives.The lability of the Tbdms ethers to various reagents enables selective deprotection of the hydroxyl side-chains assembly, desirable, e.g., for phosphorylation of glycosylation.
- Fischer, Peter M.
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p. 7605 - 7608
(2007/10/02)
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