Article
Chemistry, Organic
Michal M. Wieclaw, Bartlomiej Furman
Summary: The direct asymmetric synthesis of tetrazole-functionalized 1-deoxynojirimycin derivatives from simple sugars was achieved via a Schwartz's reagent-mediated reductive amide functionalization followed by a variant of the Ugi-azide multicomponent reaction. The anomeric configurations of two products were confirmed by X-ray analysis. Additionally, interesting further transformations of the title products were described, along with surprising observations regarding the mechanism of their formation.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Piotr Szczesniak, Barbara Grzeszczyk, Bartlomiej Furman
Summary: An efficient method has been developed for the synthesis of amino-modified iminosugars, such as ADMDP or higher nojirimycin derivatives, through partial reduction in sugar-derived lactams and tandem stereoselective nucleophilic addition of cyanide or a silyl enol ether according to specific control models.
Article
Biochemistry & Molecular Biology
Anna Osuch-Kwiatkowska, Slawomir Jarosz
Summary: D-Glucose was converted into an orthogonally protected open-chain derivative with different blocks at the C1 and C6 terminal positions, leading to intermediate products of D-gluco-configuration and L-gulo isomer.
CARBOHYDRATE RESEARCH
(2022)
Article
Chemistry, Organic
Somnath, Rajashaker Bantu, Jagadeesh Babu Nanubolu, G. Jithender Reddy, B. V. Subba Reddy
Summary: This article presents a novel strategy for the synthesis of iminosugars using the Ugi reaction. The method allows for the catalyst-free formation of iminosugars in good yields. The reaction proceeds through the formation of a bicyclic N-acyl-iminium intermediate and the subsequent attack of an isonitrile, resulting in the formation of dihydroxypyroglutamic acid, a core structure found in many biologically important natural products.
Article
Chemistry, Organic
Yi-Xian Li, Jun-Zhe Wang, Yuna Shimadate, Maki Kise, Atsushi Kato, Yue-Mei Jia, George W. J. Fleet, Chu-Yi Yu
Summary: The C-7 fluorinated derivatives of casuarine and australine, important polyhydroxylated pyrrolizidines, were successfully synthesized using organocatalytic stereoselective alpha-fluorination of aldehydes as a key step. This strategy can also be applied to the synthesis of challenging fluorinated iminosugars and carbohydrates. Docking studies revealed that the potent inhibitions of trehalase and amyloglucosidase by the fluorinated polyhydroxylated pyrrolizidines are mainly due to the interaction of fluorine atoms in these iminosugars with the amino acid residues of the corresponding enzymes. Additionally, unusual anion-pi interactions were established between the C-7 fluoride and a hydrophobic pocket in amyloglucosidase. These unexpected docking modes and structure-activity relationship studies highlight the significance of fluorination in the design of polyhydroxylated pyrrolizidine glycosidase inhibitors.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Piotr Szczesniak, Bartlomiej Furman
Summary: An efficient method for the synthesis of bicyclic iminosugars has been developed, involving partial reduction and tandem stereoselective nucleophile addition to form polyhydroxylated cyclic amines. Introduction of vinyl or allyl groups to the iminosugar leads to diene derivatives that can be further converted to polyhydroxylated pyrrolizidine, indolizidine, and quinozilidine derivatives through ring-closing metathesis reaction, with good to excellent yields. This method has been successfully applied to the formal synthesis of hyacinthacine A(2), a polyhydroxylated pyrrolizidine alkaloid.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Francesca Clemente, Macarena Martinez-Bailen, Camilla Matassini, Amelia Morrone, Silvia Falliano, Anna Caciotti, Paolo Paoli, Andrea Goti, Francesca Cardona
Summary: This study reports the synthesis of five new trihydroxypiperidine iminosugars and identifies compound 12 as a potential therapeutic agent with chaperoning properties for GM1 gangliosidosis patients.
Article
Chemistry, Organic
Dong Zi, Yuna Shimadate, Jun-Zhe Wang, Atsushi Kato, Yi-Xian Li, Yue-Mei Jia, George W. J. Fleet, Chu-Yi Yu
Summary: A series of DAB-peptide and DAB-dipeptide derivatives were synthesized from d-tartrate-derived nitrone 18. Four of the DAB peptides were found to be weak and selective bovine liver beta-galactosidase inhibitors, with the compound 23b showing the most potent beta-galactosidase inhibition. Molecular docking studies revealed different docking modes of compound 23b compared to other DAB peptides, and partial similarity of compound 23b to DGJ.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Enno Aeissen, Aaron R. von Seggern, Marc Schmidtmann, Jens Christoffers
Summary: In this study, cyclopenta-, benzo-, and cyclohepta[b]-annulated azepane scaffolds were efficiently synthesized from optically active cyclic alpha-allyl-beta-oxoesters. The synthesis involves two steps: ruthenium-catalyzed olefin cross metathesis with acrylonitrile, followed by palladium-catalyzed dihydrogenation consisting of hydrogenation, reductive amination, and cyclization reactions. The annulated azepanes with relative trans-configuration were obtained selectively. The amino and ester functionalities further provide opportunities for diversification of the scaffolds. The enantiopurity and relative trans-configurations of the products were confirmed by chiral phase GLC analysis and X-ray crystallography, respectively.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Daniel Diez-Iriepa, Isabel Iriepa, Francisco Lopez-Munoz, Jose Marco-Contelles, Dimitra Hadjipavlou-Litina
Summary: This study reports the synthesis and evaluation of nine novel heterobisnitrones as antioxidants, with hBN9 showing the highest activity. The results suggest that hBN9 may be a potent antioxidant with potential anti-inflammatory effects.
Article
Biochemistry & Molecular Biology
Martina De Angelis, Ludovica Primitivo, Federica Lizzio, Sonia Agostinelli, Carla Sappino, Ilaria Ben Romdan, Luciano Bonanni, Andrea D'Annibale, Roberto Antonioletti, Alessandra Ricelli, Giuliana Righi
Summary: In this study, we have described a versatile approach for synthesizing the pyrrolizidine alkaloids skeleton by modifying our original strategy used for pyrrolidine iminosugars synthesis. The key steps involve the regio- and stereoselective azidolysis of a suitable chiral vinyl epoxide and the asymmetric dihydmxylation of the corresponding azido alcohol. The synthesized iminosugars possess complete stereocontrol and hold significant importance due to their wide range of biological properties.
CARBOHYDRATE RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Veronica E. Manzano, Lucas Dada, Maria Laura Uhrig, Oscar Varela
Summary: Monosaccharide derivatives with conjugated double bond and carbonyl (sugar enones or enuloses) are important tools in synthesis, serving as starting materials or intermediates for a wide range of biologically and pharmacologically active natural or synthetic compounds. Efforts are focused on developing more efficient and diastereoselective synthetic methods for enone preparation. Enuloses are versatile due to the varied reactions that can occur with alkene and carbonyl double bonds, including halogenation, nitration, epoxidation, reduction, and addition. The synthesis of enuloses and the Michael addition of sulfur nucleophiles to produce thiosugars or thiodisaccharides, along with chemical modifications of the addition products to obtain biologically active compounds, are discussed.
CARBOHYDRATE RESEARCH
(2023)
Article
Chemistry, Organic
Diego Nunez-Villanueva, Adrian Plata-Ruiz, Ignacio Romero-Muniz, Ignacio Martin-Perez, Lourdes Infantes, Rosario Gonzalez-Muniz, Mercedes Martin-Martinez
Summary: Beta-turns are common secondary structures in proteins. A diastereopure azepane-derived amino acid has been found to effectively induce beta-turns when incorporated at the i + 1 position in peptide models. The analysis of the self-assembly of these peptides reveals a supramolecular helical arrangement.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Jilai Wu, Lulu Su, Tongguan Jia, Xiaoming Xu, Yaxin Cui, Chao Wei, Xiaoliu Li, Hua Chen
Summary: A simple and efficient one-pot synthesis method has been developed for the stereoselective synthesis of novel fused multicyclic iminosugars with structural diversity, using an aza-Diels-Alder mechanism. The adaptability of this method has been demonstrated by using a variety of aromatic amines and tosylated sugars.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Takuya Sagawa, Hirokazu Kobayashi, Chinatsu Murata, Yukatsu Shichibu, Katsuaki Konishi, Mineo Hashizume, Atsushi Fukuoka
Summary: Chitin is a rich marine biomass that can be used to produce renewable organonitrogen compounds. This study focuses on the catalytic conversion of 2-acetamide-2-deoxysorbitol (ADS) into oxazolidinones. Specifically, the isomer 2,3-OX, which possesses specific chirality suitable for antibiotic applications, was selectively obtained with a high yield using the ubiquitous base catalyst KHCO3. DFT calculations revealed that innermolecular hydrogen bonds in the transition states play a crucial role in the selective formation of 2,3-OX.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2022)
Article
Chemistry, Organic
J. Bouquet, N. Auberger, R. Ashmus, D. King, A. Bordes, N. Fontelle, S. Nakagawa, Z. Madden, C. Proceviat, A. Kato, J. Desire, D. J. Vocadlo, Y. Bleriot
Summary: The synthesis and evaluation of seven-membered iminosugars derived from a 3S-acetamido-4R,5R,6S-trihydroxyazepane scaffold as inhibitors of functionally related exo-N-acetylhexosaminidases were reported. The study explored the effects of epimerization and C-alkylation at specific positions, leading to the identification of selective inhibitors for different hexosaminidases.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Katsuki Takashima, Takuya Okada, Atsushi Kato, Yuhei Yamasaki, Takeshi Sugouchi, Shin-ichi Akanuma, Yoshiyuki Kubo, Ken-ichi Hosoya, Hiroyuki Morita, Takuya Ito, Takeshi Kodama, Genzoh Tanabe, Naoki Toyooka
Summary: In this study, the divergent synthesis of various poison-frog alkaloids was achieved using stereoselective reactions, resulting in the discovery of potential compounds with inhibitory activity against the cholinergic nervous system.
Article
Chemistry, Medicinal
Jun-Zhe Wang, Yuna Shimadate, Maki Kise, Atsushi Kato, Yue-Mei Jia, Yi-Xian Li, George W. J. Fleet, Chu-Yi Yu
Summary: Enantiomeric series of C-4 hydroxymethyl depleted DAB and LAB derivatives were synthesized and evaluated as potent and selective GCase inhibitors. The study provides a strategy for the development of drugs for the treatment of acid beta-glucosidase related diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jun-Zhe Wang, Bin Cheng, Atsushi Kato, Maki Kise, Yuna Shimadate, Yue-Mei Jia, Yi-Xian Li, George W. J. Fleet, Chu-Yi Yu
Summary: This study designed and synthesized two series of C-4 alkylated and arylated LAB and DAB derivatives, and evaluated their activity against various glycosidases. The results revealed potential inhibitory effects of some derivatives and provided guidance for drug design and development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Yi-Xian Li, Jun-Zhe Wang, Yuna Shimadate, Maki Kise, Atsushi Kato, Yue-Mei Jia, George W. J. Fleet, Chu-Yi Yu
Summary: The C-7 fluorinated derivatives of casuarine and australine, important polyhydroxylated pyrrolizidines, were successfully synthesized using organocatalytic stereoselective alpha-fluorination of aldehydes as a key step. This strategy can also be applied to the synthesis of challenging fluorinated iminosugars and carbohydrates. Docking studies revealed that the potent inhibitions of trehalase and amyloglucosidase by the fluorinated polyhydroxylated pyrrolizidines are mainly due to the interaction of fluorine atoms in these iminosugars with the amino acid residues of the corresponding enzymes. Additionally, unusual anion-pi interactions were established between the C-7 fluoride and a hydrophobic pocket in amyloglucosidase. These unexpected docking modes and structure-activity relationship studies highlight the significance of fluorination in the design of polyhydroxylated pyrrolizidine glycosidase inhibitors.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
David M. Campkin, Yuna Shimadate, Barbara Bartholomew, Paul Bernhardt, Robert J. Nash, Jennette A. Sakoff, Atsushi Kato, Michela Simone
Summary: Novel tetrachlorinated phthalimide analogues with boron-pinacolate ester group were synthesized and evaluated for their potential applications in glycosidase modulation and cancer treatment, showing promising potency and selectivity for certain molecules.
Article
Biochemistry & Molecular Biology
Olumayokun A. Olajide, Victoria U. Iwuanyanwu, Owolabi W. Banjo, Atsushi Kato, Yana B. Penkova, George W. J. Fleet, Robert J. Nash
Summary: This study found that idoBR1, a cucumber-derived iminosugar amino acid, could dose-dependently reduce the inflammatory responses in LPS-activated microglia cells. These findings suggest that idoBR1 may have anti-inflammatory effects and could be further investigated for its potential in other neurodegenerative diseases.
Article
Biotechnology & Applied Microbiology
Akihide Yoshihara, Yota Takamatsu, Susumu Mochizuki, Hiromi Yoshida, Ryoji Masui, Ken Izumori, Shigehiro Kamitori
Summary: In this study, the structural and biochemical characteristics of transketolase from the thermophilic bacterium Thermus thermophilus HB8 (TtTK) were investigated. TtTK showed remarkable thermostability and efficiently catalyzed the formation of 7-carbon ketoses from various sugars. The results demonstrate the potential of TtTK as an enzyme producing a rare sugar, heptulose.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Chemistry, Medicinal
Dong Zi, Ying-Ying Song, Tian-Tian Lu, Maki Kise, Atsushi Kato, Jun-Zhe Wang, Yue-Mei Jia, Yi-Xian Li, George W. J. Fleet, Chu-Yi Yu
Summary: A series of alpha-1-C-alkyl DAB and LAB derivatives have been designed as analogues of broussonetine W and assayed as glycosidase inhibitors. Introducing substituents on the terminal aryl or hydroxyl groups decreased their alpha-glucosidase inhibitions but improved their inhibitions of bovine liver beta-glucosidase and beta-galactosidase. The compounds also showed potent inhibitions of human lysosome beta-glucosidase and docking calculations revealed novel binding modes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Atsushi Kato, Izumi Nakagome, Maki Kise, Kousuke Yoshimura, Nobutada Tanaka, Robert J. Nash, George W. J. Fleet, Yota Kobayashi, Hayato Ikeda, Takuya Okada, Naoki Toyooka
Summary: This study presents a strategy for designing a practical ligand for lysosomal acid alpha-glucosidase (GAA) with a focus on N-alkyl derivatives of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB). The optimized N-4'-(p-trifluoromethylphenyl)butyl-DAB (5g) showed significantly higher affinity for GAA compared to N-butyl-DAB (3f). Docking analysis revealed the accommodation of the phenyl group of 5g in a lipophilic pocket and the stabilizing effect of the p-trifluoromethyl group.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Brendan J. Byatt, Atsushi Kato, Stephen G. Pyne
Summary: The 10 glyphaeaside alkaloids isolated from the roots of Glyphaea brevis were originally believed to be piperidine-based 1-C-alkylated iminosugars with different ring configurations. However, further studies showed that glyphaeaside C is a pyrrolidine-based iminosugar with a revised ring configuration. Synthesis experiments were conducted to confirm the structure of glyphaeaside C and related derivatives. The inhibitory activity of these compounds against glycosidases was also examined, revealing their potential as inhibitors.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Jerome Desire, Zakaria Debbah, David Gueyrard, Jerome Marrot, Yves Bleriot, Atsushi Kato
Summary: A series of L-iminosugar C,C-glycosides containing an allyl group and various substituents at the pseudoanomeric position were synthesized and evaluated for their glycosidase inhibition activity. The compounds adopted a 1C4 conformation and showed weaker glycosidase inhibition compared to previously reported branched L-iminosugars. However, some compounds exhibited micromolar inhibition of human lysosome β-glucocerebrosidase, indicating their potential as potent CGase inhibitors by modifying the structure/length of the pseudoanomeric substituents.
CARBOHYDRATE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Huawen Peng, Kaicheng Yu, Xufei Liu, Jiapeng Li, Xiangguo Hu, Qiang Zhao
Summary: Researchers solved the problems of susceptibility to chlorine degradation and low permeance in current polyamide lithium extraction nanofiltration membranes by designing a new quaternized-spiro piperazine monomer and translating its beneficial properties into large-area membranes. The new membranes have high permeance and chlorine resistance, and their performance is stable even after 400 hours of immersion in sodium hypochlorite. The high performance is attributed to the spiral conformation and secondary amine structures of the monomer.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Dong Zi, Yuna Shimadate, Jun-Zhe Wang, Atsushi Kato, Yi-Xian Li, Yue-Mei Jia, George W. J. Fleet, Chu-Yi Yu
Summary: A series of DAB-peptide and DAB-dipeptide derivatives were synthesized from d-tartrate-derived nitrone 18. Four of the DAB peptides were found to be weak and selective bovine liver beta-galactosidase inhibitors, with the compound 23b showing the most potent beta-galactosidase inhibition. Molecular docking studies revealed different docking modes of compound 23b compared to other DAB peptides, and partial similarity of compound 23b to DGJ.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
