Article
Chemistry, Multidisciplinary
Hao Yu, Zachary P. Sercel, Samir P. Rezgui, Jonathan Farhi, Scott C. Virgil, Brian M. Stoltz
Summary: This study describes a synthetic approach to aleutianamine and highlights its potent biological activity against human pancreatic cancer cells, making it a potential candidate for therapeutic development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Yun-Peng Zou, Zheng-Lin Lai, Meng-Wei Zhang, Jianzhao Peng, Shuai Ning, Chuang-Chuang Li
Summary: The first total synthesis of (+/-)- and (-)-daphnilloninB, a daphnicyclidin-type alkaloid with a novel hexa-cyclic core, was achieved through a series of chemical reactions. The B/C/D ring system was efficiently constructed using a mild intramolecular cycloaddition and a GrubbsII catalyst-catalyzed radical cyclization. The E/F fused ring system was synthesized via a diastereo-selective intramolecular Pauson-Khand reaction. The challenging hexa-cyclic core was reassembled from a hexa-cyclic framework found in calyciphylline A-type Daphniphyllum alkaloids through a unique Wagner-Meerwein rearrangement.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Karli R. Holman, Allison M. Stanko, Matthieu J. R. Richter, Sean S. Feng, Mahideremariyam N. Gessesse, Sarah E. Reisman
Summary: In this study, radical and transition metal-catalyzed cascade cyclization strategies were explored for the synthesis of the tetracyclic core of the augustamine-type Amaryllidaceae alkaloids. The successful synthesis of noraugustamine and the development of an oxidative Heck/aza-Wacker cascade that forms multiple bonds and a quaternary carbon center in a single step were achieved.
Article
Chemistry, Multidisciplinary
Remi Andres, Qian Wang, Jieping Zhu
Summary: A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been achieved by several key steps, including a catalyst-controlled asymmetric Pictet-Spengler reaction, oxidative cleavage, and intramolecular nucleophilic addition. The synthesis confirmed the absolute configuration of these natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Guang Li, Nicolas Gaeng, Cyril Piemontesi, Qian Wang, Jieping Zhu
Summary: The enantioselective total synthesis of three monoterpene indole alkaloids was successfully achieved by introducing chirality, using MOM ether as a protective group, and employing a domino reaction to construct the indole and piperidine rings. The synthesis confirmed the absolute configuration of these natural products according to the biogenetic hypothesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Shen Tan, Yu-Tao He, Ping Lan, Martin G. Banwell, Lorenzo V. White
Summary: A seven-step total synthesis of (-)-thebaine from simple, commercially available starting materials is reported. Key steps include successive coupling and substitution reactions, as well as a photochemical hydroamination reaction.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Multidisciplinary
Nicholas L. Magann, Erin Westley, Madison J. Sowden, Michael G. Gardiner, Michael S. Sherburn
Summary: The total synthesis of three diastereomeric matrine natural products is reported, which involved the formation of a tetracyclic framework using acyclic precursors and orchestrated intramolecular cycloadditions. The three natural products were obtained through late-stage hydrogenation and strain-release redox epimerizations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Shiyuan Kang, Yinxia Wu, Min Hu, Ying Ma, Xiangdi Huang, Zhen Hao, Xiujuan Li, Wen Chen, Hongbin Zhang
Summary: The asymmetric total synthesis of vinorine, a complex cage-like alkaloid, has been achieved using a flexible approach. Key steps in this synthesis involve a rearrangement/cyclization reaction to form the functional 9-azabicyclo[3.3.1]nonane scaffold, a high yield indole annulation to create a common intermediate for sarpagine-ajamaline type alkaloids, and a rearrangement reaction to construct the C15-C20 bond.
Article
Chemistry, Applied
Heng-Tong Qu, Zeng-Hui Wu, Guo-Chen Zhong, Yan-Chun Zhang, Cheng-Tao Feng, Kun Xu
Summary: An aerobic Mn(III)-catalyzed one-pot three-component synthesis of 5-cyano-pyrazolo[1,5-a]pyrimidines has been developed, which relies on the synergistic combination of Strecker reaction and oxidatively-induced 6 pi-azacyclization. This protocol offers a step-economic, regioselective, and functionally tolerant strategy to obtain 5-cyano-pyrazolo[1,5-a]pyrimidines, distinct from previous reports using toxic cyanating agents or multistep synthesis.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Alexander J. Hughes, Steven D. Townsend
Summary: In this study, we achieved the gram-scale total synthesis of (+/-)-ibogamine in nine steps and with an overall yield of 24%. The key steps include a Mitsunobu fragment coupling and macrocyclic Friedel-Crafts alkylation to establish the nitrogen-containing core of ibogamine. Additionally, a regio- and diastereoselective hydroboration reaction was used to simultaneously form the tetrahydroazepine and isoquinuclidine ring systems via sulfonamide deprotection and intramolecular cyclization.
Article
Chemistry, Organic
Yuta Nakashima, Taichi Inoshita, Mariko Kitajima, Hayato Ishikawa
Summary: The first asymmetric total synthesis of the Lycopodium alkaloid senepodine F, containing a decahydroquinoline ring (AB-ring) and a quinolizidine ring (CD-ring) connected by a methylene tether, has been achieved. The key steps of this synthesis involve an organocatalytic asymmetric Diels-Alder reaction, a diastereoselective intramolecular aza-Michael reaction, and an intramolecular SN2 cyclization to construct nitrogen-containing heterocycles. Furthermore, this total synthesis allowed for the reassignment of the stereochemistry of the decahydroquinoline ring in senepodine F.
Review
Biochemistry & Molecular Biology
Elzbieta Wojaczynska, Franz Steppeler, Dominika Iwan, Marie-Christine Scherrmann, Alberto Marra
Summary: Organocatalysis is a valuable tool for asymmetric synthesis of biologically active compounds, avoiding the use of harmful metals and allowing reactions in benign solvents without the need for anhydrous conditions. In addition to l-proline and cinchona alkaloids, carbohydrates have also been used as organocatalysts in recent decades. This review provides a comprehensive overview of the preparation and catalytic properties of sugar-based organocatalysts.
Article
Chemistry, Multidisciplinary
K. C. Nicolaou, Saiyong Pan, Yogesh Shelke, Qiuji Ye, Dipendu Das, Stephan Rigol
Summary: This study reveals a new synthetic strategy for the total synthesis of norhalichondrin B using a highly convergent approach and a reverse approach for the synthesis of cyclic ether structural motifs. The reported total synthesis was achieved by synthesizing two almost equally complex fragments, with an essential epimerization of the C16 stereocenter occurring concurrently with a simple acid-induced deprotection. This unprecedented strategy within the halichondrin family could have practical applications for synthesizing other natural or designed analogues.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Ryohei Hanzawa, Haruhiko Fuwa
Summary: A collective asymmetric total synthesis of marine tricyclic alkaloids, cylindricines A-H, as well as the proposed structures of cylindricines I and J, was accomplished from a single common spirocyclic pyrrolidine intermediate in a concise manner. A tandem chemoselective oxidation/intramolecular aza-Michael addition/epimerization strategy was utilized to successfully construct the tricyclic skeleton. This work presents a versatile synthetic approach to the cylindricine family of marine tricyclic alkaloids.
Article
Chemistry, Organic
Dongfang Jiang, Yang Chen, Shaozhong Wang
Summary: The total synthesis of marine alkaloids cystodytins A-K has been achieved using commercially available compounds in five to six steps. The synthesis involves an oxidative amination-cyclization reaction and a copper(II)-catalyzed enantioselective Henry reaction. The absolute configuration of the stereogenic centers in cystodytins D-I and K has been determined for the first time, while the stereochemistry of the olefin unit in the side chain of cystodytins H and I has been revised.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
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
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.
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.
Editorial Material
Biochemistry & Molecular Biology
Francesca Cardona, Camilla Parmeggiani, Camilla Matassini
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
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
Francesca Clemente, Maria Giulia Davighi, Camilla Matassini, Francesca Cardona, Andrea Goti, Amelia Morrone, Paolo Paoli, Tomas Tejero, Pedro Merino, Martina Cacciarini
Summary: Piperidine-based photoswitchable derivatives have been developed as potential pharmacological chaperones for Gaucher disease. The compounds inhibit human GCase in a non-competitive manner, with the interaction occurring at an allosteric site. Experiments on GD patients' fibroblasts showed a moderate activity enhancement of the mutant GCase, indicating the potential for further improvement.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Macarena Martinez-Bailen, Camilla Matassini, Francesca Clemente, Cristina Faggi, Andrea Goti, Francesca Cardona
Summary: This study presents a novel stereoselective synthetic method for pentahydroxyazepaneiminosugars. The approach involves a crucial osmium-catalyzed aminohydroxylation reaction of allylic alcohols derived from the addition of vinylmagnesium bromide to a d-mannose-derived aldehyde. This reaction forms a new C-N bond with complete regio- and stereocontrol based on the tethering approach, followed by intramolecular reductive amination to obtain the desired azepanes. This is the first application of the osmium-catalyzed tethered aminohydroxylation reaction in the synthesis of iminosugars.
Article
Chemistry, Organic
Maria Giulia Davighi, Camilla Matassini, Andrea Goti, Marta Ferraroni, Andrea Angeli, Claudiu T. Supuran, Francesca Cardona
Summary: A series of novel mono- and three-tailed derivatives containing a sugar or an iminosugar with a terminal benzenesulfonamide were synthesized to investigate their inhibitory activity and selectivity towards human carbonic anhydrases (hCAs). Copper-catalyzed azide-alkyne cycloaddition followed by an amine-isothiocyanate coupling was used for synthesis. Biological assays revealed that the single-tailed sugar-based compound 10 exhibited better inhibition against three different hCAs compared to the reference compound (AAZ), while the three sugar tailed derivatives 25 and 26 showed potent and selective inhibition. The iminosugar single-tailed compound 31 exhibited promising and selective inhibitory activity towards hCA VII (Ki = 9.7 nM).
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Francesca Buco, Camilla Matassini, Costanza Vanni, Francesca Clemente, Paolo Paoli, Cosimo Carozzini, Alice Beni, Francesca Cardona, Andrea Goti, Sergio Enrique Moya, Maria Grazia Ortore, Patrizia Andreozzi, Amelia Morrone, Marco Marradi
Summary: In this study, gold nanoparticles decorated with monosaccharides or sulfated ligands were designed as multivalent inhibitors for the enzyme GALNS associated with Morquio A. The beta-D-galactoside-coated AuNPs showed the most effective inhibition of GALNS activity. In the case of mixed-ligand AuNPs, alpha-D-mannosides exhibited a synergistic effect with sulfated ligands, leading to significantly stronger inhibition of GALNS.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
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)
