- 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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p. 8297 - 8302
(2021/03/01)
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- Investigation for the cyclization efficiency of linear tetrapeptides: Synthesis of tentoxin B and dihydrotentoxin
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Investigation of the cyclization efficiency of N-methyl linear tetrapeptides using a molecular modeling study and chemical synthesis is described. The linear peptide with two N-methyl groups, MeAla-Leu-MePhe-Gly, forms γ-turn like conformation with the am
- Sato, Ryota,Oyama, Kie,Konno, Hiroyuki
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supporting information
p. 6173 - 6181
(2018/09/17)
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- A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus
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Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2-6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7-13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.
- Bai, Xiaohui,Niu, Youhong,Zhu, Jingjing,Yang, An-Qi,Wu, Yan-Fen,Ye, Xin-Shan
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p. 1163 - 1170
(2016/03/01)
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- A total synthesis of a highly N-methylated cyclodepsipeptide [2S,3S-Hmp]-aureobasidin L using solid-phase methods
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[2S,3S-Hmp]-Aureobasidin L 2 has been successfully synthesised through a combination of solution- and solid-phase peptide synthesis. All of the Fmoc-protected residues including a depsidipeptide, Fmoc-MeVal-Hmp-OH, were prepared in solution phase. Chain e
- Maharani, Rani,Brownlee, Robert T.C.,Hughes, Andrew B.,Abbott, Belinda M.
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p. 2351 - 2358
(2014/04/03)
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- Fluorenylmethoxycarbonyl-N-methylamino acids synthesized in a flow tube-in-tube reactor with a liquid-liquid semipermeable membrane
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Both steps of the N-methylation of 9-fluorenylmethoxycarbonyl (Fmoc) amino acids were carried out in a microstructured tube-in-tube reactor equipped with a semipermeable Teflon AF 2400 membrane as the inner tubing. In the first step, gaseous formaldehyde
- Buba, Annette E.,Koch, Stefan,Kunz, Horst,Loewe, Holger
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supporting information
p. 4509 - 4513
(2013/07/26)
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- Enantioselective total synthesis of eudistomidins G, H, and I
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Asymmetric first total synthesis of eudistomidins G, H, and I, tetrahydro-β-carboline alkaloids from the Okinawan marine tunicate Eudistoma glaucus, has been accomplished with the Bischler-Napieralski reaction and the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configurations of eudistomidins G, H, and I were confirmed from comparison of the 1H and 13C NMR, and CD spectral data of synthetic and natural eudistomidins G, H, and I, respectively.
- Ishiyama, Haruaki,Yoshizawa, Kazuaki,Kobayashi, Jun'ichi
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p. 6186 - 6192
(2012/08/27)
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- A novel synthesis of N-but-3-enyl-α- and β-amino acids
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N-But-3-enyl-α- and β-amino acids can be prepared by cleaving 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones in the presence of allylsilanes and boron trifluoride etherate at room temperature in good to excellent yields. Georg Thieme Verlag Stuttgart.
- Van Nguyen,Brownlee, Robert T. C.,Hughes, Andrew B.
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experimental part
p. 1991 - 1998
(2010/03/24)
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- Improving oral bioavailability of peptides by multiple N-methylation: Somatostatin analogues
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Full methyl jacket? A complete library of the N-methylated somatostatin cyclopeptidic analogue Veber-Hirschmann peptide cyclo(-PFwKTF-) has been prepared with the aim of improving its bioavailability. Several analogues from the library were found to bind
- Biron, Eric,Chatterjee, Jayanta,Ovadia, Oded,Langenegger, Daniel,Brueggen, Joseph,Hoyer, Daniel,Schmid, Herbert A.,Jelinek, Raz,Gilon, Chaim,Hoffman, Amnon,Kessler, Horst
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p. 2595 - 2599
(2008/12/23)
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- Facile synthesis of Fmoc-N-methylated α- and β-amino acids
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A highly efficient and environmentally friendly synthesis of Fmoc-N-methyl α- and β-amino acids from the corresponding Fmoc-amino acid, via intermediate oxazolidinones/oxazinanones, has been developed. Microwave heating for 3 min was required for the synt
- Govender, Thavendran,Arvidsson, Per I.
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p. 1691 - 1694
(2007/10/03)
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- Mild regeneration of the carboxylic group of amino acid alkyl esters by aqueous methanolic sodium hydrogen carbonate via 5-oxazolidinones
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A simple racemization-free procedure allows the regeneration of the carboxylic acid group of amino acid alkyl esters by way of an intermediate 5-oxazolidinone which is hydrolyzed by treatment with sodium hydrogen carbonate in aqueous methanol.
- Allevi, Pietro,Anastasia, Mario
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p. 7663 - 7665
(2007/10/03)
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- Microwave accelerated efficient synthesis of N-fluorenylmethoxycarbonyl/t-butoxycarbonyl/benzyloxycarbonyl-5- oxazolidinones
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The synthesis of N-protected 5-oxazolidinones using amino acids, paraformaldehyde and p-toluene sulfonic acid in a minimum amount of toluene accelerated by microwave irradiation for 3 min in high yield is described.
- Tantry, Subramanyam J.,Kantharaju,Suresh Babu, Vommina V.
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p. 9461 - 9462
(2007/10/03)
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- Synthesis of 9-Fluorenylmethyloxycarbonyl-Protected N-Alkyl Amino Acids by Reduction of Oxazolidinones
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A new two-step synthesis of Fmoc-protected N-alkyl amino acids has been developed.The first step involves acid-catalyzed condensation of an Fmoc-protected amino acid with an aldehyde to form an oxazolidinone.This intermediate is then reduced with triethyl
- Freidinger, Roger M.,Hinkle, Jeffery S.,Perlow, Debra S.,Arison, Byron H.
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