Review
Chemistry, Multidisciplinary
Artem Drogalin
Summary: This review discusses the synthesis of D-swainsonine and substituted D-swainsonines over the past 18 years, focusing on the choice of synthetic methods and introduction of relevant substituents.
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
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, Multidisciplinary
Roger A. Ashmus, Yang Wang, Manuel Gonzalez-Cuesta, Dustin T. King, Ben Tiet, Xi Chen, Yanping Zhu, Bryce Kirk, Jose M. Garcia Fernandez, Carmen Ortiz Mellet, Robert Britton, David J. Vocadlo
Summary: Glycoside hydrolases (GHs) are enzymes that play a role in various diseases. Researchers are searching for selective GH inhibitors to understand their functions and explore their therapeutic potential. In this study, a concise synthesis of iminosugar inhibitors of α-N-acetyl-galactosaminidase (α-NAGAL) was described. The newly synthesized inhibitor DGJNGuan exhibited potent and selective inhibition of α-NAGAL both in vitro and within cells, making it a useful tool compound for studying the physiological roles of α-NAGAL.
CHEMISTRY-A EUROPEAN JOURNAL
(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, 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, 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
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, Medicinal
Milos Trajkovic, Milos Pavlovic, Filip Bihelovic, Zorana Ferjancic, Radomir N. Saicic
Summary: A chiral pyrrolidine derivative with 3 contiguous stereocenters was synthesized in only 2 synthetic steps from achiral precursors using a tactical combination of proline catalyzed aldol reaction followed by intramolecular reductive amination. This product, available in both enantiomeric forms, was further utilized as a common intermediate in total syntheses of biologically active iminosugars.
NATURAL PRODUCT COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Tomas Klunda, Michal Hricovini, Sergej Sestak, Juraj Kona, Monika Polakova
Summary: In this study, N-alkylated polyhydroxypyrrolidines were synthesized and tested as inhibitors of Golgi alpha-mannosidase II (GMIIb). The potency of the inhibitors varied depending on the alkyl chain length and capping functional group, with amidines showing the highest activity. Molecular docking and quantum mechanics calculations revealed the importance of alkyl chain length in the interactions with the target enzyme.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tereza Cristina Santos Evangelista, Oscar Lopez, Adrian Puerta, Miguel X. Fernandes, Sabrina Baptista Ferreira, Jose M. Padron, Jose G. Fernandez-Bolanos, Magne O. Sydnes, Emil Lindback
Summary: The synthesis of four heterodimers connecting a 1-deoxynojirimycin moiety with a benzotriazole scaffold using the copper(I)-catalysed azide-alkyne cycloaddition was reported. These heterodimers showed preferential inhibition against butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) in the micromolar concentration range. The most potent inhibitor of BuChE demonstrated a mixed inhibition mode, with the benzotriazole and 1-deoxynojirimycin moiety accommodated in the catalytic anionic site and peripheral anionic site of AChE, respectively. However, the binding mode to BuChE was different, with the benzotriazole moiety accommodated in the catalytic anionic site.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Correction
Chemistry, Organic
Irene Conforti, Alberto Marra
Summary: This paper corrects the information about iminosugars as glycosyltransferase inhibitors, providing new perspectives and evidence.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Costanza Vanni, Francesca Clemente, Paolo Paoli, Amelia Morrone, Camilla Matassini, Andrea Goti, Francesca Cardona
Summary: The synthesis of five new multivalent derivatives of a trihydroxypiperidine iminosugar was achieved through copper catalyzed alkyne-azide cycloaddition. These multivalent compounds showed much more potent inhibitory effects on lysosomal GCase, with the trivalent derivative demonstrating a 2-fold recovery of enzyme activity on Gaucher patient fibroblasts. Furthermore, thermal denaturation experiments indicated its ability to enhance stability of the recombinant enzyme used in therapy.
Article
Multidisciplinary Sciences
Hongjian Gao, Ao Fan
Summary: A green synthetic route was developed for the synthesis of enzyme active hydroxypiperidine iminosugars, resulting in good overall yields. Heterogeneous catalysts and environmentally friendly reagents were utilized in critical reactions, with the Au/Al2O3 catalyst being easily recovered and reused without loss of activity.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Organic
Yadagiri Thummala, Ashok K. Morri, Galla V. Karunakar, Venkata Ramana Doddi
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Chemistry, Applied
Yadagiri Thummala, Galla V. Karunakar, Venkata Ramana Doddi
ADVANCED SYNTHESIS & CATALYSIS
(2019)
Article
Chemistry, Multidisciplinary
Soumya Poshala, Sanjeeva Thunga, Saikumar Manchala, Hari Prasad Kokatla
Article
Chemistry, Organic
Sanjeeva Thung, Soumya Poshala, Naveenkumar Anugu, Ramaiah Konakanchi, Satheesh Vanaparthi, Hari Prasad Kokatla
TETRAHEDRON LETTERS
(2019)
Article
Chemistry, Organic
Ashok K. Morri, Yadagiri Thummala, Ramesh Adepu, Gangavaram V. M. Sharma, Subhash Ghosh, Venkata Ramana Doddi
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2019)
Article
Chemistry, Organic
Sivaparwathi Golla, Soumya Poshala, Ravinder Pawar, Hari Prasad Kokatla
TETRAHEDRON LETTERS
(2020)
Article
Chemistry, Organic
Yadagiri Thummala, Chittala Emmaniel Raju, Dalovai Purnachandar, Gottam Sreenivasulu, Venkata Ramana Doddi, Galla V. Karunakar
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Ashok K. Morri, Yadagiri Thummala, Subhash Ghosh, Venkata R. Doddi
Summary: This unique method demonstrates the efficacy of urea for generating alkynyl radicals from 1-bromoalkynes under metal-free conditions. Urea enables the transformation of 1,1-dirbomoalkenes or 1-bromoalkynes to 1,3-diynes via Homolytic Alkynyl Substitution (HAS), and shows efficiency in synthesizing disubstituted alkyne through cross-coupling reactions. The detection of short-lived alkynyl radicals during the reactions suggests the potential of this method for further studies.
Article
Chemistry, Applied
Naveenkumar Anugu, Sanjeeva Thunga, Sivaparwathi Golla, Hari Prasad Kokatla
Summary: A new regioselective method has been developed for the insertion of isocyanide into the C2-H position of quinoline N-oxides catalyzed by molecular iodine, resulting in rapid access to quinoline 2-formamides with exceptional functional group tolerance, broad substrate scope, and 100% atom-economy. This metal-free reaction has synthesized a library of 33 N-(2-quinolinyl)formamides, which may have potential applications in pharmaceuticals and synthetic chemistry.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Sivaparwathi Golla, Naveenkumar Anugu, Swathi Jalagam, Hari Prasad Kokatla
Summary: A transition-metal and hydride-free reductive aldol reaction has been developed using rongalite for the synthesis of biologically active 3,3'-disubstituted oxindoles from isatin derivatives. This method offers high yields of 3-hydroxy-3-hydroxymethyloxindoles and 3-amino-3-hydroxymethyloxindoles, making it suitable for gram scale synthesis with cost-effective rongalite.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Sivaparwathi Golla, Hari Prasad Kokatla
Summary: A transition metal-and hydride-free protocol has been developed for the chemoselective reduction of alpha-keto esters and alpha-keto amides using rongalite as a reducing agent via a radical mechanism. This method offers high yields and compatibility with other reducible functionalities, and the reducing agent used is inexpensive.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Naveenkumar Anugu, Sanjeeva Thunga, Soumya Poshala, Hari Prasad Kokatla
Summary: A logic-based approach using quinoline N-oxides as a replacement for the carboxylic acid component in the Ugi reaction has been developed. The unique reactivity of N-oxides enables the efficient synthesis of biologically active compounds.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Sivaparwathi Golla, Swathi Jalagam, Soumya Poshala, Hari Prasad Kokatla
Summary: A new synthetic method using rongalite as a reducing agent and donor has been reported for the functionalization of 2-oxindoles without the use of transition metals and hydrides, with yields ranging from 65% to 95%. This method has advantages such as one-pot reaction, low cost, mild reaction conditions, and applicability to large-scale synthesis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Shiva Krishna Moodapelly, Yerramsetti Nanaji, Gangavaram V. M. Sharma, Kanaparthy Suneeel, Venkata Ramana Doddi
Summary: This study demonstrates an efficient synthesis of 1,3-diynes directly from 1,1-dibromoalkenes using DBU.H2O as a sole reagent and CuI catalyst, achieving high efficiency under solvent-free conditions. The proposed mechanism involves 1-bromoalkynes intermediate instead of terminal alkynes.
Article
Chemistry, Multidisciplinary
Purnachandar Dalovai, Galla Venkata Karunakar, Vidya Damodaran Nadar, Venkata Ramana Doddi, Suneel Kanaparthy
Summary: An efficient synthetic method for accessing substituted aminobenzophenones has been developed, catalyzed by gold and forming a new C-C bond through intramolecular 6-endo-dig cyclization. The substituted aminobenzophenones were obtained in good to excellent yields.
JOURNAL OF CHEMICAL SCIENCES
(2021)
