研究领域

Organic Chemistry

My research group's interests are in the areas of synthesis, catalysis and the design of molecular systems. We are developing new catalytic asymmetric carbon-carbon bond forming reactions to rapidly access complex molecules from simple molecules and then apply these methods to the construction of important targets like natural products and clinically used drugs. We are also working to uncover how some of the most basic functions of living systems can be observed in purely synthetic systems with the long-term goal of understanding what is different about living and non-living matter and how to construct new molecular machines. Asymmetric cross-coupling reactions My group has developed a series of Cu- and Rh-catalyzed asymmetric reactions that form C-C bonds under easily accessible conditions. We are particularly interested in developing new catalytic asymmetric variations of widely used cross-coupling reactions like Suzuki-Miyaura coupling that will allow rapid access to complex three dimensional architectures with high diastereo- and enantiomeric control. As well as developing methods we perform mechanistic studies to understand how these transformations work, and have developed an approach to understanding the sources of asymmetric induction so that we can design new ligands and catalysts. We have applied these methods to the synthesis of clinically used drugs and natural products such as fulvestrant, tafluprost, niraparib and the taxol core. Self-replicating systems We are investigating different avenues to learn how small molecules may self-replicate, and have developed new systems involving self-replicating micelles and vesicles. The mechanisms of these processes are very important to us and we use kinetics and other mechanistic studies to understand how these systems can be controlled. We have made many intriguing discoveries during this research, for example how to couple self-reproduction to secondary processes and how ‘selection’ and ‘evolution’ may occur within lipid replicators (i.e. without nucleotides or other biologically based template mechanisms) and we are currently working to understand how lipid self-replication can be used to drive novel macromolecular and microscopic phenomena. Molecular machines and how to transmit information and work across length scales We have previously performed structure-activity relationship studies of how to control photoisomerization in dynamic molecular systems, built systems capable of performing macroscopic work, and learned how to control self-replication in supramolecular systems. Our current aims are to understand how molecular signals can transmit information, or be use to drive processes at different length scales. We are especially interested in how chirality can be amplified to control the geometry and properties of nanoscale materials. We also aim to understand how dynamic supramolecular and microscale systems may be constructed, maintained and controlled using the chemistry of small molecules.

近期论文

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Acceleration of lipid reproduction by emergence of microscopic motion.Babu, D, Scanes, RJH, Plamont, R, Ryabchun, A, Lancia, F, Kudernac, T, Fletcher, SP, Katsonis, N 19 May 2021 doi 10.1038/s41467-021-23022-1 Additions to Racemates: A Strategy for Developing Asymmetric Cross-Coupling Reactions Goetzke, FW, Fletcher, SP 12 April 2021 doi 10.1055/s-0040-1706033 Coupled Metabolic Cycles Allow Out-of-Equilibrium Autopoietic Vesicle Replication. Engwerda, AHJ, Southworth, J, Lebedeva, MA, Scanes, RJH, Kukura, P, Fletcher, SP November 2020 doi 10.1002/anie.202007302 Dissipative self-assembly, competition and inhibition in a self-reproducing protocell model Post, EAJ, Fletcher, SP 21 September 2020 doi 10.1039/d0sc02768e Oligomerization Driven by Phase Separation Myrgorodska, I, Colomer, I, Fletcher, SP September 2020 doi 10.1002/syst.201900059 A molecular assembler that produces polymers. Engwerda, AHJ, Fletcher, SP 19 August 2020 doi 10.1038/s41467-020-17814-0 Emergence and Rearrangement of Dynamic Supramolecular Aggregates Visualized by Interferometric Scattering Microscopy. Lebedeva, MA, Palmieri, E, Kukura, P, Fletcher, SP 18 August 2020 doi 10.1021/acsnano.0c02414 Coupled Metabolic Cycles Allow Out-of-Equilibrium Autopoietic Vesicle Replication Engwerda, A, Southworth, J, Lebedeva, M, Scanes, R, Kukura, P, Fletcher, S 11 August 2020 doi 10.1002/ange.202007302 Synthesis of the Taxol Core via Catalytic Asymmetric 1,4-Addition of an Alkylzirconium Nucleophile. Wang, JYJ, Fletcher, SP June 2020 doi 10.1021/acs.orglett.0c01165 Enantiomerically enriched tetrahydropyridine allyl chlorides Karabiyikoglu, S, Brethome, AV, Palacin, T, Paton, RS, Fletcher, SP 28 April 2020 doi 10.1039/d0sc00377h An Asymmetric Suzuki-Miyaura Approach to Prostaglandins: Synthesis of Tafluprost. Kučera, R, Goetzke, FW, Fletcher, SP April 2020 doi 10.1021/acs.orglett.0c00745 Selection from a pool of self-assembling lipid replicators. Colomer, I, Borissov, A, Fletcher, SP 10 January 2020 doi 10.1038/s41467-019-13903-x Ligand Design for Asymmetric Catalysis: Combining Mechanistic and Chemoinformatics Approaches Ardkhean, R, Fletcher, SP, Paton, RS 1 January 2020 doi 10.1007/3418_2020_47 Highly Enantioselective Hiyama Cross-Coupling via Rh-Catalyzed Allylic Arylation of Racemic Allyl Chlorides Gonzalez, J, Schafer, P, Fletcher, SP 28 October 2019 doi 10.1021/acs.organomet.9b00197 Highly enantioselective rhodium-catalyzed cross-coupling of boronic acids and racemic allyl halides. González, J, van Dijk, L, Goetzke, FW, Fletcher, SP October 2019 doi 10.1038/s41596-019-0209-8 Desymmetrization of meso-bisphosphates via rhodium catalyzed asymmetric allylic arylation Jacques, R, Hell, AML, Pullin, RDC, Fletcher, SP 31 August 2019 doi 10.1016/j.tet.2019.130560 Enantio- and Diastereoselective Suzuki-Miyaura Coupling with Racemic Bicycles. Goetzke, FW, Mortimore, M, Fletcher, SP August 2019 doi 10.1002/anie.201906478 Retooling Asymmetric Conjugate Additions for Sterically Demanding Substrates with an Iterative Data-Driven Approach. Brethomé, AV, Paton, RS, Fletcher, SP August 2019 doi 10.1021/acscatal.9b01814 Allylic Chloro-Tetrahydropyridines: Kinetic Resolutions and Stereospecific Reactions of Enantiomerically Enriched Allyl Chlorides Karabiyikoglu, S, Brethomé, A, Palacin, T, Paton, R, Fletcher, S 28 May 2019 doi 10.26434/chemrxiv.8181686.v1 A chemically fuelled self-replicator. Morrow, SM, Colomer, I, Fletcher, SP March 2019 doi 10.1038/s41467-019-08885-9 Conformational Effects on Physical-Organic Descriptors: The Case of Sterimol Steric Parameters Brethome, AV, Fletcher, SP, Paton, RS March 2019 doi 10.1021/acscatal.8b04043 Desymmetrization of meso-bisphosphates using copper catalysis and alkylzirconocene nucleophiles. Jacques, R, Pullin, RDC, Fletcher, SP 3 January 2019 doi 10.1038/s41467-018-07871-x β-Chloroaldehydes from Trapping Zirconium Enolates Produced in Asymmetric 1,4-Additions. Wang, JYJ, Palacin, T, Fletcher, SP 31 December 2018 doi 10.1021/acs.orglett.8b03520