Article
Chemistry, Organic
Marianne B. Haarr, Oscar Lopez, Jose G. Fernandez-Bolanos, Emil Lindback, Magne O. Sydnes
Summary: The efficient synthesis of enantiomeric pairs of iminosugars with different functional groups was described, and their activities against glycosidases were tested. The DAB analogues showed enhanced activity compared to the LAB analogues, especially the D-arabino-configured amidine as a potential inhibitor of alpha-mannosidase.
SYNTHESIS-STUTTGART
(2022)
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
Chemistry, Organic
Yi-Xian Li, Jun-Zhe Wang, Atsushi Kato, Yuna Shimadate, Maki Kise, Yue-Mei Jia, George W. J. Fleet, Chu-Yi Yu
Summary: In this study, four diastereomers belonging to the family of casuarines were synthesized, with 6-epi-casuarine exhibiting enhanced inhibition of trehalase and 6,7-diepi-casuarine leading to specific inhibition of trehalase.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Valeria Pingitore, Macarena Martinez-Bailen, Ana T. Carmona, Zuzana Meszaros, Natalia Kulik, Kristyna Slamova, Vladimir Kren, Pavla Bojarova, Inmaculada Robina, Antonio J. Moreno-Vargas
Summary: Two libraries of mono- and dimeric pyrrolidine iminosugars were synthesized and screened for inhibition of enzymes from Jack beans and human lysosomal hexosaminidases, resulting in the identification of potent and selective inhibitors for human nucleocytoplasmic beta-N-acetylglucosaminidase.
BIOORGANIC 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
Chemistry, Multidisciplinary
Yao Xu, Hai-Xiang Gao, Chengkai Pan, Yue Shi, Chi Zhang, Genping Huang, Chao Feng
Summary: By using photoredox catalysis, we have achieved the (3+3) dipolar cycloaddition of nitrones with aryl cyclopropanes. This reaction exhibits excellent regio- and stereoselectivity and can be applied to a variety of aryl cyclopropane substrates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Sha Zhu, Yerri Jagadeesh, Anh Tuan Tran, Shuki Imaeda, Alisdair Boraston, Dominic S. Alonzi, Ana Poveda, Yongmin Zhang, Jerome Desire, Julie Charollais-Thoenig, Stephane Demotz, Atsushi Kato, Terry D. Butters, Jesus Jimenez-Barbero, Matthieu Sollogoub, Yves Bleriot
Summary: In the study, a pharmacological chaperone approach was explored to enhance the activity of NAGLU in patient fibroblasts affected by Mucopolysaccharidosis type IIIB. By synthesizing a library of iminosugar C-glycosides, it was found that a non-functionalized and wrongly configured beta-homoiminosugar acted as the most promising pharmacological chaperone, promoting a 2.4 fold activity enhancement of mutant NAGLU at its optimal concentration.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Alexander Aksenov, Dmitrii A. Aksenov, Nicolai A. Aksenov, Anton A. Skomorokhov, Elena Aleksandrova, Michael Rubin
Summary: This study utilized a highly efficient one-pot procedure to prepare diastereomerically selective 4'H-spiro[indole-3,5'-isoxazoles] by combining conjugate addition of Grignard reagents to (2-nitroalkenyl)indoles with subsequent Bronsted acid-assisted spirocyclization. The use of alkyl Grignard reagents provided easy access to 4'-alkylsubstituted derivatives that are difficult to obtain by other means.
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
Chemistry, Applied
Hao Yuan, Dong-Liu Lu, Cui Liang, Dong-Liang Mo
Summary: Various spirooxindole-benzo[d]oxazoles and dihydrobenzofurans were successfully synthesized via transition metal-free [3 + 2] cycloaddition and selective rearrangement. The substituent on the N-vinyl group of the nitrone was found to control the [1,3]- or [3,3]-rearrangement of the cycloadduct due to steric effects. This method demonstrates broad substrate scope, good functional group tolerance, controllable rearrangement, and diverse oxindole scaffolds.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Applied
Rayhane Hammami, Pascale Maldivi, Christian Philouze, Sebastien Carret, Benjamin Darses, Soufiane Touil, Jean-Francois Poisson
Summary: A variety of 4-phosphinylpyrrolidin-3-ones were synthesized via a [3+2] cycloaddition reaction between aryl aldonitrones and phosphinylallenes. The products were obtained as unique 4,5-trans diastereomers in yields ranging from 47% to 80% for 23 examples. Chiral racemic allenes exhibited a moderate 2:1 to 4:1 2,5-diastereoselectivity. Under the reaction conditions, the cycloadducts undergo a rearrangement to selectively afford the corresponding pyrrolidin-3-ones. DFT calculations provided insights into the mechanism involving the homolytic cleavage of the N-O bond of the cycloadduct.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Lin-Feng Yang, Ming Zhang, Yuna Shimadate, Atsushi Kato, Tian-Yang Liu Hou, Yi-Xian Li, Yue-Mei Jia, George W. J. Fleet, Chu-Yi Yu
Summary: A series of iso-allo-DNJ and L-isoDALDP derivatives were synthesized through sequential and highly diastereoselective Ho and Hentry reactions, as well as aziridinium intermediate-mediated ring rearrangement. The glycosidase inhibition assay revealed that four of them were selective alpha-glucosidase inhibitors, with compound 30 showing the strongest inhibition activity (IC50 = 9.3 μM). Molecular docking study showed different docking modes of the derivatives compared to their parent compounds, and compound 30 showed similarity to isofagomine.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
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
Biochemistry & Molecular Biology
Alejandro Puet, Gema Dominguez, Francisco Javier Canada, Javier Perez-Castells
Summary: The study demonstrated the synthesis of new cyclopropane-containing piperidines from L-serine and L-alanine, with the possibility of mimicking L-fucose. The final compounds, bearing S configurations, were tested as potential inhibitors of different glycosidases, showing low inhibition activity but selectivity and unexpected activity enhancement in some cases.
Article
Chemistry, Organic
Qing-Hui Shi, Yu-Heng Wang, Zi-Yue Chen, Xi-Rui Wang, Wen-Hui Zhang, Fang-Li Tian, Li-Jun Peng, Ying Zhou, Xiong-Li Liu
Summary: This study describes an unexpected discovery of accessing bispiro[oxindole-oxazinane] hybrids inspired by natural products dehydrocostus lactone/parthenolide through a skeletal-editing step of formal oxygen atom insertion into a carbon-nitrogen bond. These structurally diverse and medicinally important compounds, containing up to six adjacent stereocentres including two quaternary spiro-stereocentres, were successfully synthesized in two steps with excellent results. This protocol represents the first example of skeletal editing of a pyrrolidine skeleton to a 1,2-oxazinane skeleton and expands the applicability of single-atom skeletal-editing technologies.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Franca M. Cordero, Alberto Brandi
Summary: This paper describes a unique method for preparing beta-lactam and beta-homoproline derivatives that are not easily accessible through traditional processes. The method was developed based on a serendipitous discovery made in the lab in 2000, involving heating a reaction mixture. Investigation of the process revealed an alternative synthetic method based on acid-induced rearrangement, with experimental and computational studies presented on the mechanism involved.
Article
Chemistry, Organic
Debora Pratesi, Andrea Sodini, Camilla Matassini, Francesca Cardona, Andrea Angeli, Fabrizio Carta, Marta Ferraroni, Claudiu T. Supuran, Andrea Goti
Summary: Synthesis of twelve new aza-sugar-benzenesulfonamides by connecting benzenesulfonamides to a triazole armed aza-sugar resulted in significant effects on the inhibition profile of human carbonic anhydrases. Some new compounds demonstrated selective inhibitory effects, with four of them showing particular efficacy on therapeutically relevant hCAs II and VII isoforms.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Lorenzo Briccolani-Bandini, Marco Pagliai, Franca M. Cordero, Alberto Brandi, Gianni Cardini
Summary: The regioselectivity in the 1,3-dipolar cycloaddition between cyclic nitrone and methylenecyclopropane has been studied through DFT calculations. The electrostatic interaction plays a central role in the regioselectivity of the reactions, with the electronic effect of substituents determining the polarization of the alkene double bond and interaction with nitrones.
JOURNAL OF PHYSICAL CHEMISTRY A
(2021)
Article
Chemistry, Organic
Francesca Clemente, Camilla Matassini, Sara Giachetti, Andrea Goti, Amelia Morrone, Macarena Martinez-Bailen, Sara Orta, Pedro Merino, Francesca Cardona
Summary: A straightforward synthetic strategy was reported for preparing trihydroxypiperidine azasugars as potential inhibitors of the lysosomal enzyme glucocerebrosidase. The best ligand for GCase, compound 15, was obtained in remarkable yields through a series of reactions starting from low-cost D-mannose. MD simulations helped identify the chair conformation with the best binding affinity.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anna Ranzenigo, Franca M. Cordero, Martina Cacciarini, Mogens Brondsted Nielsen
Summary: Photochromic molecules can form high-energy isomers through photoisomerization, showing potential applications in solar energy storage. Substituents at the ortho position of DHA-Ph can significantly increase the half-life of VHF-Ph. However, ortho-bridged DHA-DHA may lead to degradation.
Review
Biochemistry & Molecular Biology
Giacomo Biagiotti, Ilaria Perini, Barbara Richichi, Stefano Cicchi
Summary: The article discusses the success of the rational bottom-up approach to nanostructured carbon materials and the discovery of the importance of doping with heteroatoms, as well as the significance of controlling geometry and position of the heteroatoms. These factors influence the chemical-physical properties and applications of the compounds, transforming fundamental research into cutting-edge technology research.
Article
Biochemistry & Molecular Biology
Costanza Vanni, Anne Bodlenner, Marco Marradi, Jeremy P. Schneider, Maria de los Angeles Ramirez, Sergio Moya, Andrea Goti, Francesca Cardona, Philippe Compain, Camilla Matassini
Summary: In this study, water dispersible gold nanoparticles coated with iminosugar deoxynojirimycin (DNJ) and simple monosaccharides were prepared, leading to enhanced inhibitory activity towards Jack bean alpha-mannosidase. A novel strategy involving longer amphiphilic linker and trimeric presentation of the inhitope was employed, resulting in a significant increase in inhibitory potency.
Editorial Material
Biochemistry & Molecular Biology
Francesca Cardona, Camilla Parmeggiani, Camilla Matassini
Article
Biochemistry & Molecular Biology
Elena Petricci, Simone Zurzolo, Camilla Matassini, Samuele Maramai, Francesca Cardona, Andrea Goti, Maurizio Taddei
Summary: A general method for the synthesis of pyrrolizidine derivatives using intramolecular hydroaminomethylation protocol under microwave dielectric heating is reported. The use of ethanol as a solvent provides environmentally friendly conditions, and the ligand/catalyst system can be recycled without significant impact on yield.
Review
Chemistry, Medicinal
Macarena Martinez-Bailen, Francesca Clemente, Camilla Matassini, Francesca Cardona
Summary: Pharmaceutical chaperones (PCs) are small compounds that can bind and stabilize misfolded proteins, helping them regain their native conformation and biological activity. They are especially beneficial in treating lysosomal storage disorders (LSDs) caused by genetic mutations. However, despite the importance of the GCase enzyme in treating LSDs and neurological disorders, no PC for this enzyme has been approved for market use. This review highlights the efforts made in the past 7 years to identify new PCs for the GCase enzyme, with a focus on glycomimetic-based compounds.
Article
Chemistry, Multidisciplinary
Donatella Giomi, Jacopo Ceccarelli, Antonella Salvini, Marika Pinto, Alberto Brandi
Summary: The reduction of aromatic nitro compounds can be efficiently achieved using Wang-PQM catalyst and NaBH4, leading to high yields of azo and/or hydrazoarenes.
Article
Chemistry, Multidisciplinary
Margherita Cacaci, Giacomo Biagiotti, Gianluca Toniolo, Martin Albino, Claudio Sangregorio, Mirko Severi, Maura Di Vito, Damiano Squitieri, Luca Contiero, Marco Paggi, Marcello Marelli, Stefano Cicchi, Francesca Bugli, Barbara Richichi
Summary: The worldwide crisis of bacterial resistance to traditional antibiotics has prompted research into the development of silver-based nanomaterials with enhanced antibacterial activity. This study describes the synthesis of three different silver nanoparticle hybrids using organic and inorganic supports. The tuning of the silver nanoparticles' shape and size according to the type of support used was also investigated. The resulting composite materials showed effective antibacterial activity against clinically relevant multi-drug-resistant bacteria and the fungus Candida albicans.
Article
Chemistry, Organic
Paolo Della Sala, Costanza Vanni, Carmen Talotta, Luca Di Marino, Camilla Matassini, Andrea Goti, Placido Neri, Sergej Sestak, Francesca Cardona, Carmine Gaeta
Summary: The synthesis of multivalent ligands anchored to resorcinarene scaffolds showed significant multivalent effects towards GMIIb, a recombinant Drosophila homolog of over-expressed human Golgi alpha-mannosidase II, indicating promising inhibitory potency. Computational studies helped to understand the origin of the multivalent effect and the relative inhibitory potency of the new architectures.
ORGANIC CHEMISTRY FRONTIERS
(2021)
