A Synthesis Programme at Cambridge
Lead Research Organisation:
University of Cambridge
Department Name: Chemistry
Abstract
The research presented in this proposal, encompasses a broad range of challenging projects. The total syntheses will require the development of existing reactions and the invention of new processes. We will develop new synthetic methods and new tools for molecular synthesis. There is much to commend an integrated programme of science as presented in this document. The desire for more efficient syntheses stimulates the discovery of new reactivities to solve particular problems. New reactions can open up areas for total synthesis and analogue generation that were previously inaccessible. These drivers impact on the development of new methods for synthesis. The added value that arises from having a closely coupled programme containing the development of new synthetic methods, new ways of performing reactions and total synthesis is considerable. All these disciplines will drive the creative process. It is undoubtedly a grand challenge, but one we feel is worthy of investment.
Organisations
People |
ORCID iD |
Steven Ley (Principal Investigator) |
Publications
Battilocchio C
(2013)
Flow Synthesis and Biological Studies of an Analgesic Adamantane Derivative That Inhibits P2X7-Evoked Glutamate Release.
in ACS medicinal chemistry letters
Newton S
(2012)
Asymmetric Homogeneous Hydrogenation in Flow using a Tube-in-Tube Reactor
in Advanced Synthesis & Catalysis
Hornung C
(2010)
A Palladium Wall Coated Microcapillary Reactor for Use in Continuous Flow Transfer Hydrogenation
in Advanced Synthesis & Catalysis
Frost JR
(2012)
Convergent total syntheses of callipeltosides A, B, and C.
in Angewandte Chemie (International ed. in English)
Oelke AJ
(2010)
Total synthesis of chloptosin.
in Angewandte Chemie (International ed. in English)
Newton S
(2014)
Accelerating spirocyclic polyketide synthesis using flow chemistry.
in Angewandte Chemie (International ed. in English)
Polyzos A
(2010)
The Continuous-Flow Synthesis of Carboxylic Acids using CO 2 in a Tube-In-Tube Gas Permeable Membrane Reactor
in Angewandte Chemie International Edition
Ley SV
(2013)
Camera-enabled techniques for organic synthesis.
in Beilstein journal of organic chemistry
Baumann M
(2011)
An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals.
in Beilstein journal of organic chemistry
Roper KA
(2011)
The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors.
in Beilstein journal of organic chemistry
Baxendale IR
(2013)
The synthesis of neurotensin antagonist SR 48692 for prostate cancer research.
in Bioorganic & medicinal chemistry
Bourne S
(2012)
Flow Chemistry Syntheses of Styrenes, Unsymmetrical Stilbenes and Branched Aldehydes
in ChemCatChem
Browne D
(2013)
Continuous Cold without Cryogenic Consumables: Development of a Convenient Laboratory Tool for Low-Temperature Flow Processes
in Chemical Engineering & Technology
Lange H
(2011)
A breakthrough method for the accurate addition of reagents in multi-step segmented flow processing
in Chemical Science
Kraus H
(2013)
Synthesis of spongistatin 2 employing a new route to the EF fragment
in Chemical Science
O'Brien M
(2011)
Hydrogenation in flow: Homogeneous and heterogeneous catalysis using Teflon AF-2400 to effect gas-liquid contact at elevated pressure
in Chemical Science
Oelke AJ
(2011)
Total synthesis of chloptosin: a dimeric cyclohexapeptide.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Ley SV
(2009)
Total synthesis of rapamycin.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Carter CF
(2011)
Diastereoselective chain-elongation reactions using microreactors for applications in complex molecule assembly.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Battilocchio C
(2013)
A Machine-Assisted Flow Synthesis of SR48692: A Probe for the Investigation of Neurotensin Receptor-1
in Chemistry - A European Journal
Petersen TP
(2012)
The oxygen-mediated synthesis of 1,3-butadiynes in continuous flow: using Teflon AF-2400 to effect gas/liquid contact.
in ChemSusChem
Gross U
(2014)
A General Continuous Flow Method for Palladium Catalysed Carbonylation Reactions Using Single and Multiple Tube-in-Tube Gas-Liquid Microreactors
in European Journal of Organic Chemistry
Koos P
(2012)
Continuous stream processing: a prototype magnetic field induced flow mixer
in Green Processing and Synthesis
Battilocchio C
(2013)
Flow-Based, Cerium Oxide Enhanced, Low-Level Palladium Sonogashira and Heck Coupling Reactions by Perovskite Catalysts
in Israel Journal of Chemistry
Guetzoyan L
(2014)
Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography
in Med. Chem. Commun.
Oelke AJ
(2011)
Piperazic acid-containing natural products: isolation, biological relevance and total synthesis.
in Natural product reports
Smith CJ
(2011)
Flow synthesis of organic azides and the multistep synthesis of imines and amines using a new monolithic triphenylphosphine reagent.
in Organic & biomolecular chemistry
Carter CF
(2009)
Synthesis of acetal protected building blocks using flow chemistry with flow I.R. analysis: preparation of butane-2,3-diacetal tartrates.
in Organic & biomolecular chemistry
Venturoni F
(2010)
The application of flow microreactors to the preparation of a family of casein kinase I inhibitors
in Organic & Biomolecular Chemistry
Hartwig J
(2014)
Continuous flow chemistry: a discovery tool for new chemical reactivity patterns.
in Organic & biomolecular chemistry
Cranwell PB
(2012)
Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal-Knorr pyrrole formation and gas concentration measurement by inline flow titration.
in Organic & biomolecular chemistry
Smith C
(2011)
A fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3-triazoles
in Organic & Biomolecular Chemistry
Hopkin MD
(2013)
An expeditious synthesis of imatinib and analogues utilising flow chemistry methods.
in Organic & biomolecular chemistry
Alves L
(2015)
A practical deca-gram scale ring expansion of (R)-(-)-carvone to (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1
in Organic & Biomolecular Chemistry
Koos P
(2011)
Teflon AF-2400 mediated gas-liquid contact in continuous flow methoxycarbonylations and in-line FTIR measurement of CO concentration.
in Organic & biomolecular chemistry
O'Brien M
(2012)
A prototype continuous-flow liquid-liquid extraction system using open-source technology.
in Organic & biomolecular chemistry
Hu DX
(2012)
Continuous multiple liquid-liquid separation: diazotization of amino acids in flow.
in Organic letters
Francais A
(2010)
Total synthesis of the anti-apoptotic agents iso- and bongkrekic acids.
in Organic letters
Ingham RJ
(2012)
A "catch-react-release" method for the flow synthesis of 2-aminopyrimidines and preparation of the Imatinib base.
in Organic letters
O'Brien M
(2010)
Flow ozonolysis using a semipermeable Teflon AF-2400 membrane to effect gas-liquid contact.
in Organic letters
Browne DL
(2011)
A new enabling technology for convenient laboratory scale continuous flow processing at low temperatures.
in Organic letters
Newby J
(2014)
Reconfiguration of a Continuous Flow Platform for Extended Operation: Application to a Cryogenic Fluorine-Directed ortho -Lithiation Reaction
in Organic Process Research & Development
Carter C
(2010)
ReactIR Flow Cell: A New Analytical Tool for Continuous Flow Chemical Processing
in Organic Process Research & Development
Pastre J
(2013)
Scaling Up of Continuous Flow Processes with Gases Using a Tube-in-Tube Reactor: Inline Titrations and Fanetizole Synthesis with Ammonia
in Organic Process Research & Development
Browne DL
(2012)
Continuous flow reaction monitoring using an on-line miniature mass spectrometer.
in Rapid communications in mass spectrometry : RCM
Ley S
(2009)
Enantioselective Synthesis of the Lyngbouilloside Macrolactone Core
in Synlett
Description | New methods and new tools have been developed for the synthesis of molecules of biological interest. The three major themes of this work are Natural Product Synthesis, New Synthesis Methods, and Emerging Technology and New Tools for Chemical Synthesis. Natural Product Synthesis So far the total syntheses of iso- and bongkrekic acids, chloptosin and O-methyl siphonazole have been accomplished. New Synthesis Methods New synthesis methods that have so far been invented and developed to provide improvements or strategic advantages over existing protocols in organic chemistry include the use of pyrrolidinyl-tetrazole as a versatile organocatalyst in enantioselective synthesis including nitrocyclopropanation reactions and the addition of malonates to enones, and the use of biocatalysis for 'greener' chemical processes. Emerging Technology and New Tools for Chemical Synthesis. We have had great success in developing user-friendly gas reactors for introducing a range of gases into a liquid stream. We have collaborated with instrument manufacturers to invent new in-line reaction monitoring equipment with diagnostic capabilities, and new apparatus has been devised to solve current problems in cryogenic flow chemistry. Novel monolithic constructs have been prepared and used as alternatives to solution-based reagents and substrates. |
Exploitation Route | The scientific community has benefitted by the discovery and demonstration that biocatalysis can be used for 'greener' chemical processes thus reducing the impact on the environment and society as a whole. Our work Emerging Technology and New Tools for Chemical Synthesis has provided the community new equipment that, through our collaboration with manufacturers, can be purchased so as to enable users to be able to reproduce our work and for them to make their own discoveries. |
Sectors | Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Description | Our work has benefitted local equipment manufacturers who we collaborated with us to invent new in-line reaction monitoring equipment with diagnostic capabilities, and new apparatus to solve current problems in cryogenic flow chemistry. Novel monolithic constructs have been prepared and used as alternatives to solution-based reagents and substrates. Global citizens have also benefitted due to reduced resource consumption for the preparation of molecules of biological interest. The large number of students and staff who were supported on the grant made very significant contributions to the science achieved, eg publications as well as receiving an outstanding training. The post-docs have now moved on to pursue careers in academia or industry. |
First Year Of Impact | 2008 |
Sector | Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Title | Other Research Output |
Description | New / Enhanced Equipment / Facility |
Type Of Technology | New/Improved Technique/Technology |
Year Produced | 2010 |
Impact | Development of fluorination methods using continuous-flow microreactors |
Title | Other Research Output |
Description | New / Improved Product / Process |
Type Of Technology | New Material/Compound |
Year Produced | 2010 |
Impact | A fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3-triazoles |
Title | Other Research Output |
Description | New / Improved Technique / Technology |
Type Of Technology | New/Improved Technique/Technology |
Year Produced | 2010 |
Impact | Development of fluorination methods using continuous-flow microreactors |