Article
Chemistry, Physical
Jian-Hua Liu, Qing Zhou, Yao Lin, Zhu-Lian Wu, Tian Cai, Wei Wen, Yan-Min Huang, Qi-Xiang Guo
Summary: In this study, a highly efficient atom-economic asymmetric alpha-allylation method using chiral-aldehyde/palladium catalyst was reported. This method enables the asymmetric alpha-allylation of different 1,3-dienes and allenes with N-unprotected amino acid esters, leading to the synthesis of alpha,alpha-disubstituted chiral alpha-amino acid esters with high efficiency, good yields, and stereoselectivities. No N-allylation byproducts were observed in these reactions. Two reaction models were proposed based on mechanistic control experiments. Overall, this work demonstrates a new approach for preparing structurally diverse chiral amino acids and provides insights for developing chiral-aldehyde catalytic systems.
Article
Chemistry, Multidisciplinary
Guangying Tan, Fritz Paulus, Angel Renteria-Gomez, Remy F. Lalisse, Constantin G. Daniliuc, Osvaldo Gutierrez, Frank Glorius
Summary: Radical addition reactions of olefins are widely used in organic synthesis, but mainly limited to polymerization or 1,2-difunctionalization. This study presents an unprecedented radical relay 1,4-oxyimination of two electronically differentiated olefins using a class of bifunctional oxime carbonate reagents through an energy transfer strategy. The reaction is highly selective and diverse, providing rapid access to valuable products.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Lu Xiao, Xin Chang, Hui Xu, Qi Xiong, Yanfeng Dang, Chun-Jiang Wang
Summary: Cooperative bimetallic catalysis enables regio-/stereodivergent asymmetric alpha-allylations of aldimine esters. By employing Et3B as the key activator, racemic allylic alcohols can be directly ionized to form Pd or Ir-pi-allyl species in the presence of achiral Pd or chiral Ir complexes, respectively. The reaction exhibits high regioselectivity and excellent stereoselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Dandan Yang, Hai Huang, He Zhang, Li-Ming Yin, Mao-Ping Song, Jun-Long Niu
Summary: The study achieved the Co-H-catalyzed intermolecular hydroamination of unactivated alkenes with various amine electrophiles by introducing a removable directing group. The catalytic system showed substrate-dependent regioselectivity, broad substrate scope, and simplified reaction conditions, providing a general and flexible protocol for the preparation of various amino acid derivatives.
Article
Chemistry, Organic
Georgina Kirby, Guillaume Prestat, Farouk Berhal
Summary: Herein, an atom-economical intermolecular iron-catalyzed oxyamination of alkenes is reported. The insertion of oxygenated and nitrogenated moieties from the hydroxylamine substrate was observed with full regio- and chemo-selectivity for terminal alkenes in good yields. HFIP solvent appeared to synergistically promote the formation of the oxyaminated products with the iron catalyst. Preliminary mechanistic studies suggest a pathway involving aziridination followed by in situ ring opening.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mukesh Pappoppula, Kathryn L. Olsen, Devin R. Ketelboeter, Aaron Aponick
Summary: A highly enantioselective alkynylation of pyridine is reported. The reaction is enabled by StackPhos and proceeds with excellent regioselectivity (25 : 1), enantioselectivity (up to 99 % ee), and yield (up to 99 %). Terminal alkynes with a wide range of functional groups work well in the transformation, including acetylene gas, paving the way for the use of these feedstock starting materials to rapidly access highly useful synthetic intermediates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Zhiping Yang, Qingwei Du, Yanxin Jiang, Jun (Joelle) Wang
Summary: In this study, a highly efficient, versatile, and universal method for synthesizing gamma-amino acid and gamma-amino phosphonic acid derivatives was developed. The method allows for good yields of chiral products with high levels of enantiocontrol and regioselectivity.
Article
Chemistry, Organic
Lu-Wen Zhang, Xiao-Jun Deng, Dong-Xu Zhang, Qin-Qin Tian, Wei He
Summary: This study introduces a novel method for the synthesis of amino lactones and explores the influence of the iodoarene precatalyst structure on reaction rate, demonstrating its selective adjustment effect in aminolactonization and oxylactonization. Furthermore, the feasibility of asymmetric aminolactonization catalyzed by a chiral iodoarene precatalyst was verified through preliminary experiments.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Minghui Zhu, Qinglong Zhang, Weiwei Zi
Summary: The study presents a dual-metal catalyzed diastereodivergent coupling method for the synthesis of beta-amino alcohols with multiple stereoisomers, enabling the concise preparation of natural products such as mycestericins F and G.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Jin-Tao Xia, Ling Li, Xiang-Ping Hu
Summary: A copper-catalyzed asymmetric decarboxylative propargylic alkylation has been successfully achieved, allowing for the highly stereoselective formation of acyclic vicinal tri- and tetrasubstituted stereocenters. This strategy has demonstrated high potential in resolving challenges present in traditional catalytic propargylic alkylation by preparing optically active quaternary alpha-amino acid esters with chiral tertiary propargylic moieties in high yields and good to excellent diastereo- and enantioselectivities.
Article
Multidisciplinary Sciences
Hao Zheng, Chang-Hui Liu, Shi-Yu Guo, Gu-Cheng He, Xiang-Ting Min, Bo-Chao Zhou, Ding-Wei Ji, Yan-Cheng Hu, Qing-An Chen
Summary: This study reports an electrochemically driven method for the efficient synthesis of phosphorylated metallocenes, providing guidance for the C-H functionalization of symmetric metallocenes.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Xiangji Yang, Kemiao Hong, Sujie Zhang, Zhijing Zhang, Su Zhou, Jingjing Huang, Xinfang Xu, Wenhao Hu
Summary: In this study, an asymmetric aminohydroxylation method using hydroxylamine derivatives was developed. This method involves N-O bond activation, fragment modification, and reassembly cascade process, forming multiple bonds in one reaction. The resulting chiral compounds have two adjacent tertiary chiral centers.
Article
Chemistry, Multidisciplinary
Hiroto Uno, Koki Kawai, Taichi Araki, Motoo Shiro, Norio Shibata
Summary: Gem-difluoromethylene moieties are attractive in medicinal chemistry due to their ability to mimic other more ubiquitous functional groups. A novel asymmetric method for their construction was developed, allowing easy access to chiral 1,3-dioxanes that contain a tetrasubstituted difluoroalkyl stereogenic center. The gem-difluoro substitution pattern promotes the reaction, and various substrates were suitable for this method.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Jun Zheng, Ali Nikbakht, Bernhard Breit
Summary: A dual palladium/photoredox-catalyzed regio- and enantioselective decarboxylative hydroaminoalkylation of allenes with amino acids was reported. This method allows efficient access to protected vinyl 1,2-amino ethers with high levels of branched and enantioselectivity.
Article
Chemistry, Applied
Qian Li, Yan Liu, Can Li
Summary: English Summary: Chiral unprotected 3-amino-2-quinolinone and 2-quinolinone-based cyclic amino acids are important in the structures of drugs and bioactive molecules. A Pd(0)-catalyzed enantioselective sequential decarboxylative allylation/desymmetrization protocol is reported for the synthesis of these structures. The reaction exhibits high enantioselectivities (up to 96% ee) and good diastereoselectivities (up to 15:1 dr), and the products can be further transformed into chiral 3-amino-2-quinolinone derivatives.
CHINESE JOURNAL OF CATALYSIS
(2023)
Article
Engineering, Biomedical
Fatemeh Karimi, Varsha Jagannath Thombare, Craig A. Hutton, Andrea J. O'Connor, Greg G. Qiao, Daniel E. Heath
Summary: Functionalization of surfaces with nanoclusters of ligands that bind integrin and syndecan-4 cell receptors can regulate a wide range of biophysical cell behaviors in response to shear stress. The presence of both integrin-binding ligands and syndecan-binding ligands is essential for cell alignment in the direction of flow under mechanical stimulation. Surfaces functionalized with both ligand types are more effective in scavenging cells from flow compared to surfaces functionalized with only integrin- or syndecan-binding ligands.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2021)
Article
Chemistry, Multidisciplinary
Jing Shang, Varsha J. Thombare, Carlie L. Charron, Uta Wille, Craig A. Hutton
Summary: The reaction of thiolactams with N-Boc amino acids promoted by Ag-I results in the formation of N-(alpha-aminoacyl) lactam, which can rearrange through an acyl transfer process. Deprotection of Boc leads to the ring expansion adduct, allowing for the insertion of an amino acid into the thioamide bond to generate medium-sized heterocycles. This method is demonstrated for the site-specific insertion of amino acids into cyclic peptides.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemical Research Methods
Andy Pranata, Blake Curtis, Christopher C. Waller, Karen Caldwell, Paul W. Zahra, Steven L. Karamatic, Malcolm D. McLeod
Summary: Samples of the 'dietary supplement' Furazadrol sourced through the internet have been reported to contain designer anabolic androgenic steroids, raising concerns over potential abuse in sports. Metabolism of Furazadrol in greyhounds revealed key urinary metabolites that can aid anti-doping laboratories in regulating greyhound racing.
DRUG TESTING AND ANALYSIS
(2021)
Article
Endocrinology & Metabolism
Carl Jenkinson, Reena Desai, Malcolm D. McLeod, Jonathan Wolf Mueller, Martin Hewison, David J. Handelsman
Summary: This study analyzed the contribution of sulfate and glucuronide vitamin D metabolites relative to unconjugated levels in human serum. The results showed that sulfate conjugates formed a higher proportion of circulating vitamin D metabolites compared to glucuronide conjugates. The findings suggest that a combination of both conjugated and unconjugated measurements may provide a more accurate assessment of vitamin D status.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Chemistry, Organic
Ameer B. Taresh, Craig A. Hutton
Summary: A novel method for lactam stapling of Asp/Lys-containing peptides has been developed. This method does not require coupling agents and involves the incorporation of a backbone thioamide to generate cyclic isoimide intermediates that are then trapped by Lys amine, resulting in the formation of lactam-bridged peptides with i,i+2, i,i+3, and i,i+4 spacings.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Christopher C. J. Fitzgerald, Rikard Hedman, Dimanthi R. Uduwela, Bettina Paszerbovics, Adam J. Carroll, Teresa Neeman, Adam Cawley, Lance Brooker, Malcolm D. McLeod
Summary: The study introduces a new workflow for untargeted metabolic profiling of sulfated metabolites in urine. The method utilizes high-performance liquid chromatography and mass spectrometry coupled with data dependent acquisition for analysis. The utility of the method is demonstrated in two applications: examining the urinary metabolome of a thoroughbred horse after administration of a steroid and studying the hydrolytic activity of sulfatase enzymes on human urine. The method provides a rapid tool for systematic profiling of sulfated metabolites in urine.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Organic
Komba Thomas, Olha Khymenets, Oscar J. Pozo, Malcolm D. McLeod
Summary: The convenient synthesis of two 3-glucuronide conjugates as long-term markers for endogenous androgenic anabolic steroid abuse in doping control studies is reported. These markers are resistant to enzymatic hydrolysis, which may result in them being missed by conventional GC-MS analysis protocols.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemical Research Methods
Christopher C. J. Fitzgerald, Christopher Bowen, Madysen Elbourne, Adam Cawley, Malcolm D. McLeod
Summary: The identification and confirmation of steroid sulfate metabolites in biological samples are crucial in anti-doping analysis and clinical sciences. This study utilized energy-resolved collision-induced dissociation to distinguish isomeric steroid sulfate compounds and guide the synthesis of reference materials for unambiguous confirmation of a steroid sulfate biomarker.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Multidisciplinary
Ameer B. Taresh, Craig A. Hutton
Summary: This study presents a site-specific method for preparing N-glycosylated peptides through the incorporation of a peptide backbone thioamide linkage adjacent to an Asp residue, which facilitates site-specific conversion to N-glycosylated Asn residues in peptides promoted by Ag-I.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Mohammad B. Haskali, Peter D. Roselt, Terence J. O'Brien, Craig A. Hutton, Idrish Ali, Lucy Vivash, Bianca Jupp
Summary: This study investigates the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of clinically suitable [F-18]FMZ 1. Mass spectrometry was used to identify the chemical by-products that were produced under the reaction conditions. The fully automated synthesis of [F-18]FMZ 1 using the iPhase FlexLab radiochemistry module yielded a high radiochemical purity and molar activity.
Article
Biochemistry & Molecular Biology
Bradley J. Stevenson, Andy Pranata, Malcolm D. McLeod
Summary: Steroid sulfate esters are important metabolites for various fields. Researchers used directed evolution to discover a variant, DRN-PaS, capable of efficiently hydrolyzing alpha-configured steroid sulfates, with improved activity compared to previous variants.
PROTEIN ENGINEERING DESIGN & SELECTION
(2022)
Article
Biochemistry & Molecular Biology
Andy Pranata, Sean Yamada, Sumudu Weththasinghe, Karen Caldwell, Paul W. Zahra, Steven L. Karamatic, Michael G. Gardiner, Malcolm D. McLeod
Summary: Delta 6-Methyltestosterone has been identified as the main active compound in Jungle Warfare, a dietary supplement. It has similar structure to 17 alpha-methyltestosterone but with an extra Delta 6 double bond, leading to concerns about its potential androgenic effects and abuse in sports. In vivo metabolism studies in greyhounds revealed the presence of urinary phase I and phase II metabolites, with the major phase I metabolite identified as 16 alpha,17 beta-dihydroxy-17 alpha-methylandrosta-4,6-dien-3-one. Glucuronide conjugated metabolites were also observed but resistant to hydrolysis. This study provides a method for detecting Jungle Warfare abuse in greyhounds, useful for anti-doping laboratories.
Article
Chemistry, Medicinal
Alicia Corlett, Jo-Anne Pinson, Marwa N. Rahimi, Jessica Van Zuylekom, Carleen Cullinane, Benjamin Blyth, Philip E. Thompson, Craig A. Hutton, Peter D. Roselt, Mohammad B. Haskali
Summary: This study synthesized and characterized a series of Lu-177-labeled peptides ([Lu-177]Lu-2b-4b) and compared them with the reference CCK(2)R-targeting peptide CP04 ([Lu-177]Lu-1b). [Lu-177]Lu-1b-4b showed high chemical purity, low Log D, strong binding affinity to CCK2R, and relatively high protein binding and internalization. Biodistribution studies showed that [Lu-177]Lu-2b-4b had higher uptake in tumors compared to CP04 at different time points. These findings suggest that [Lu-177]Lu-2b-4b could be a promising therapy for CCK2R-expressing tumors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Christopher C. J. Fitzgerald, Malcolm D. McLeod
Summary: This study reports a new stable isotope label for sulfate metabolites, which enables the synthesis of various SIL-steroid conjugates suitable for mass spectrometry detection and internal standards. The method was applied to investigate the mass spectrometry behavior of steroid bis(sulfate) compounds through collision-induced dissociation experiments.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Sadegh Shabani, Yuezhou Wu, Hannah G. Ryan, Craig A. Hutton
Summary: The importance of peptide modifications and the use of C-H activation/functionalization as an effective pathway for peptide modification are discussed. Bidentate directing group strategies are recognized as one of the most efficient methods for site-selective C-H activation and functionalization.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
