Article
Chemistry, Organic
Beata Zdun, Tamara Reiter, Wolfgang Kroutil, Pawel Borowiecki
Summary: We developed chemoenzymatic routes using low-cost starting materials and enzyme preparations to synthesize tenofovir. The key step involved stereoselective reduction or kinetic resolution using alcohol dehydrogenase or lipase as biocatalysts. By employing immobilized lipase in a mixture of vinyl acetate and toluene, the desired (R)-ester was obtained with high yield and optical purity. Alternatively, reduction of a ketone using lyophilized E. coli cells containing recombinant alcohol dehydrogenase resulted in excellent conversion and yield of the corresponding (R)-alcohol. The enzymatic strategy could be applied in the synthesis of tenofovir prodrug derivatives.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Alexander Rittner, Mirko Joppe, Jennifer J. Schmidt, Lara Maria Mayer, Simon Reiners, Elia Heid, Dietmar Herzberg, David H. Sherman, Martin Grininger
Summary: This study reports a strategy to introduce fluorine into complex polyketides during biosynthesis. By exchanging a domain of the polyketide synthase, the ability to incorporate fluorine during polyketide chain extension was achieved. The results demonstrate the potential application of this method in the chemoenzymatic synthesis of fluorinated compounds.
Article
Chemistry, Organic
Evan O. Romero, Jonathan C. Perkins, Jessica E. Burch, David A. Delgadillo, Hosea M. Nelson, Alison R. H. Narayan
Summary: The first asymmetric synthesis of the pentacyclic fungal marine natural product Xyloketal B is described using a chemoenzymatic strategy. The approach utilizes a biocatalytic benzylic hydroxylation and a [4 + 2] cycloaddition to access key intermediates enroute to (+)-xyloketal B. MicroED is used to confirm the relative configuration of an intermediate, and a reductive approach is employed to access a second key intermediate, culminating in the stereoselective synthesis of (+)-xyloketal B.
Review
Chemistry, Multidisciplinary
Suman Chakrabarty, Evan O. Romero, Joshua B. Pyser, Jessica A. Yazarians, Alison R. H. Narayan
Summary: The total synthesis of structurally complex natural products remains an exciting area of research, with recent advancements in biocatalysis allowing for the application of enzymes in constructing complex molecules. The utilization of enzymes alongside small molecule-based approaches has enabled concise chemoenzymatic routes to natural products, demonstrating the potential for selective oxidation reactions and late-stage diversification of complex scaffolds.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Plant Sciences
Manuel G. Schriefer, Rainer Schobert
Summary: In this study, the six recently isolated berkeleylactones E, J, K, M, N, and O were successfully synthesized for the first time using a divergent strategy from a common intermediate in the synthesis of berkeleylactone A. Key achievements include the stereoselective formation of the gamma,delta-dihydroxy-alpha,beta-unsaturated ester moiety and the development of a general protection group strategy. Additionally, a short and high-yielding formal synthesis of the commonly synthesized antibiotic A26771B was established.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Organic
Jordan T. Brazeau-Henrie, Andre R. Paquette, Allison Q. . O'Rourke, Michael G. Darnowski, Christopher N. Boddy
Summary: The total and chemoenzymatic synthesis of the depsipeptide natural product seongsanamide E, 3, is described. The synthetic C-terminal N-acetylcysteamine thioester of linear natural product 1 was macrolactonized by the excised recombinant purified seongsanamide thioesterase (Sgd-TE) domain, generating 3. Sgd-TE also effects the ring opening of 3. Chemical synthesis provided 3 through a macrolactamization strategy. This work confirms the biosynthesis of 3 and demonstrates the power of Sgd-TE as a biocatalyst.
Article
Multidisciplinary Sciences
Tao Cai, Hongbing Sun, Jing Qiao, Leilei Zhu, Fan Zhang, Jie Zhang, Zijing Tang, Xinlei Wei, Jiangang Yang, Qianqian Yuan, Wangyin Wang, Xue Yang, Huanyu Chu, Qian Wang, Chun You, Hongwu Ma, Yuanxia Sun, Yin Li, Can Li, Huifeng Jiang, Qinhong Wang, Yanhe Ma
Summary: Researchers have developed an artificial starch anabolic pathway (ASAP) in a cell-free system for starch synthesis from CO2 and hydrogen, achieving a significantly higher rate than traditional methods. This approach paves the way for future chemo-biohybrid starch synthesis from CO2.
Article
Biochemistry & Molecular Biology
Viola Kolarikova, Katerina Brodsky, Lucie Petraskova, Helena Pelantova, Josef Cvacka, Libor Havlicek, Vladimir Kren, Katerina Valentova
Summary: Ten phenolic acids were synthesized into their sulfated metabolites using chemoenzymatic and chemical methods. The study also highlighted the importance of counterions in sulfates. These products will be used as standards in metabolic studies and to determine their biological activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Maximiliano Colobbio, Enrique Pandolfi, Valeria Schapiro
Summary: This study reports the preparation of a new non-natural gabosine, in which chirality is transferred from the biotransformed metabolite of toluene. Further chemical transformations were used to introduce additional functionality and chirality to the molecule.
Article
Biochemistry & Molecular Biology
Sunaina Kiran Prabhu, Chao Li, Guanghui Zong, Roushu Zhang, Lai-Xi Wang
Summary: Core fucosylation plays a crucial role in modulating the structure and biological functions of glycoproteins, but only a few alpha-L-fucosidases are capable of removing core fucose from intact glycoproteins. This study found that bacterial alpha-L-fucosidases from Lactobacillus casei and Bacteroides fragilis could only hydrolyze truncated Fuc alpha 1,6GlcNAc-peptide substrates, while the human alpha-L-fucosidase showed activity in removing core fucose from intact glycopeptides and glycoproteins. Additionally, the human alpha-L-fucosidase was the only enzyme that exhibited some capability to remove core fucose from intact IgG antibodies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Tianzhen Li, Zijian Tan, Zijing Tang, Pi Liu, Haifeng Liu, Leilei Zhu, Yanhe Ma
Summary: An efficient method for synthesizing glycolic acid was reported in this study, utilizing a catalytic C-C coupling reaction of formaldehyde and selective oxidation, with an evolved enzyme showing improved activity at high formaldehyde concentrations.
Article
Chemistry, Physical
Mohammad Faizan Bhat, Alejandro Prats Lujan, Mohammad Saifuddin, Gerrit J. Poelarends
Summary: In this study, we report a simple chemoenzymatic synthesis route for the preparation of chiral dihydrobenzoxazinones and dihydroquinoxalinones. These methods offer high selectivity and yield, and use readily available starting materials.
Article
Chemistry, Organic
Silvia Venturi, Milos Trajkovic, Danilo Colombo, Elisabetta Brenna, Marco W. Fraaije, Francesco G. Gatti, Piero Macchi, Emilio Zamboni
Summary: This article describes the asymmetric synthesis of the most pleasant enantiomer of Jessemal fragrance, with key steps involving one-pot reduction using stereoselective redox enzymes and regioselective epoxide ring-opening using organocuprate or organolithium nucleophiles.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Wei He, Jiacheng Ni, Yu-Cai He, Jianren Ye
Summary: Efficient synthesis of furan-based chemicals from biomacromolecule using chemoenzymatic approaches has been developed in this study. Different biomass sources can produce varying concentrations of furfural, and the conversion of furfural to furfurylamine is inhibited by by-products and soluble sugars produced during the biomass conversion. The amination of furfural to furfurylamine can be achieved by using specific enzymes. This study successfully developed a chemoenzymatic strategy for the conversion of biomacromolecules into valuable furan-based products in an environmentally friendly system.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Multidisciplinary
Lifeng Sun, Pradeep Chopra, Geert-Jan Boons
Summary: A new method for the synthesis of heparan sulfate oligosaccharides composed of unsulfonated fragments of different lengths was reported. Competition binding studies showed that the length of the unsulfonated fragment modulates the binding of chemokines.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Editorial Material
Chemistry, Multidisciplinary
Antony J. Fairbanks
Article
Biochemistry & Molecular Biology
Sivasinthujah Paramasivam, Antony J. Fairbanks
CARBOHYDRATE RESEARCH
(2019)
Article
Chemistry, Organic
Xin Qiu, Antony J. Fairbanks
Article
Chemistry, Organic
Xiaoyi Wang, Anneliese S. Ashhurst, Luke J. Dowman, Emma E. Watson, Henry Y. Li, Antony J. Fairbanks, Mark Larance, Ann Kwan, Richard J. Payne
Article
Biochemistry & Molecular Biology
Antony J. Fairbanks
Summary: 2-Chloro-1,3-dimethylimidazolinium chloride (DMC) and its derivatives are valuable for selectively activating the anomeric center of unprotected reducing sugars in aqueous solution, allowing for efficient synthesis of glycosides and glycoconjugates without traditional protecting group manipulations. This mini-review explores the development and recent applications of DMC in protecting group-free synthesis.
CARBOHYDRATE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Moritz Lasse, Anja R. Stampfli, Thomas Orban, Roshit K. Bothara, Juliet A. Gerrard, Antony J. Fairbanks, Neil R. Pattinson, Renwick C. J. Dobson
Summary: The study identified acrolein modifications on hemoglobin using mass spectrometry and found that these modifications have minimal impact on the secondary structure of hemoglobin. Acrolein modifications promote the formation of crosslinked octamers and alter the response to O2 binding. The study provides qualitative evidence for potential targeted mass spectrometric or immunometric assays for acrolein modified hemoglobin as an oxidative stress marker.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Biochemistry & Molecular Biology
Michael J. Currie, Lavanyaa Manjunath, Christopher R. Horne, Phillip M. Rendle, Ramaswamy Subramanian, Rosmarie Friemann, Antony J. Fairbanks, Andrew C. Muscroft-Taylor, Rachel A. North, Renwick C. J. Dobson
Summary: The study found that the enzyme NanE may use a novel substrate-assisted proton displacement mechanism for catalysis, by re-evaluating the central role of Glu180 and the catalytic lysine, and identifying several active-site residues related to the mechanism. This discovery could be helpful in developing inhibitors for the enzyme or producing biocatalysts capable of changing the stereochemistry of molecules through enzyme engineering.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tanzeel Arif, Michael J. Currie, Renwick C. J. Dobson, Harriet L. Newson, Vivek Poonthiyil, Antony J. Fairbanks, Rachel A. North, Phillip M. Rendle
Summary: The synthesis of analogues of natural enzyme substrates can help deduce enzymatic mechanisms, as demonstrated by the investigation into N-acetylmannosamine-6-phosphate 2-epimerase. The study suggests that this enzyme may utilize a substrate-assisted proton displacement mechanism, with two novel analogues showing different binding orientations at the enzyme's active site.
CARBOHYDRATE RESEARCH
(2021)
Correction
Biochemistry & Molecular Biology
Moritz Lasse, Anja R. Stampfli, Thomas Orban, Roshit K. Bothara, Juliet A. Gerrard, Antony J. Fairbanks, Neil R. Pattinson, Renwick C. J. Dobson
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Chemistry, Organic
Xin Qiu, Daniel Chong, Antony J. Fairbanks
Summary: Unprotected sugars can be selectively acetylated in aqueous solution by stirring with acetic anhydride and a weak base, such as sodium carbonate. This reaction specifically targets the anomeric hydroxyl group of mannose, 2-acetamido, and 2-deoxy sugars and can be conducted on a large scale. However, over-reaction and the formation of product mixtures can occur due to competitive intramolecular migration of the 1-O-acetate to the 2-hydroxyl group when these two substituents are in cis configuration.
Article
Chemistry, Multidisciplinary
Xin Qiu, Anna L. Garden, Antony J. Fairbanks
Summary: In this study, a new method for synthesizing glycosides was discovered. Unprotected 2-acetamido sugars were directly converted into their oxazolines in aqueous solution using 2-chloro-1,3-dimethylimidazolinium chloride (DMC) and a suitable base. Freeze drying and acid-catalyzed reaction with an alcohol as solvent yielded 1,2-trans-glycosides in good yield. Alternatively, using an aprotic solvent system and acidic activation with an excess of unprotected glycoside as a glycosyl acceptor led to the stereoselective formation of 1,2-trans-linked disaccharides without any protecting group manipulations. Reactions using aryl glycosides as acceptors were completely regioselective, producing only (1->6)-linked disaccharides.
Meeting Abstract
Biochemistry & Molecular Biology
Sivasinthujah Srikokulan, Antony Fairbanks
Article
Chemistry, Organic
Xin Qiu, Antony J. Fairbanks
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Mikkel Haarslev Schroder Marqvorsen, Sivasinthujah Paramasivam, Ward Doelman, Antony John Fairbanks, Sander Lzaak van Kasteren
CHEMICAL COMMUNICATIONS
(2019)
