Research

Diversity-oriented synthesis

Rapid, efficient and simulataneous synthesis of diverse, stereochemically complex molecules

Diversity-oriented synthesis can be defined as the rapid, efficient and simulataneous synthesis of structurally diverse molecules.  Ideally, a diversity-oriented synthesis would yield a library of molecules which are stereochemically, substitutionally and skeletally diverse.  We have chosen to focus on the diversity-oriented synthesis of libraries of molecules which retain many of the features of natural products, since such molecules have evolved to interact productively with biological macromolecules.  Active molecules are exploited in chemical genetic studies to elucidate specific biological mechanisms.

Publications in this area:

142 Chris  Arter , Richard  Bayliss , Patrick  Collins, Daniel  Foley , Patrick  McIntyre, Frank  von Delft and Stuart  Warriner , "Construction of a Shape‐Diverse Fragment Set: Design, Synthesis and Screen against Aurora‐A Kinase", Chem. Eur. J. 2019, 25, 6831-6839
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

140 Samuel  Liver , Jacob  Masters and Adam  Nelson , "Function-driven Discovery of Bioactive Small Molecules", Chemical and Biological Synthesis: Enabling Approaches for Understanding Biology 2018, , 138-152
Keywords: "Diversity-oriented synthesis"

139 Adam  Nelson and Nicholas  Westwood, "Synthetic Tools for Elucidating Biological Mechanisms", Chemical and Biological Synthesis: Enabling Approaches for Understanding Biology 2018, , 1-7
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

138 Adam  Nelson and Nicholas  Westwood, "Chemical and Biological Synthesis: Enabling Approaches for Understanding Biology", Royal Society of Chemistry 2018, ,  ISBN: 978-1-78262-948-1
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

137 Anthony  Aimon , Mark  Dow , Tuomo  Kalliokoski, George  Karageorgis , Steve  Marsden , Remy  Morgantin , Adam  Nelson and Didier  Roche, "Translation of innovative chemistry into screening libraries: an exemplar partnership from the European Lead Factory", Drug Discovery Today 2018, 23, 1578-1583
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

136 Shiao  Chow , Samuel  Liver and Adam  Nelson , "Streamlining bioactive molecular discovery through integration and automation", Nat. Rev. Chem. 2018, 2, 174-183
Keywords: "Diversity-oriented synthesis"

135 Anthony  Aimon , Philip  Craven , Mark  Dow , Andy  Eatherton, Daniel  Foley , Tuomo  Kalliokoski, George  Karageorgis , Hugues  Lemoine, Steve  Marsden , Jacob  Masters , Remy  Morgantin , Martin  Ohsten, Didier  Roche , Nicolas  Ruiz-Llamas and Anthony  Willaume, "Realisation of small molecule libraries based on frameworks distantly related to natural products", Org. Biomol. Chem. 2018, 16, 3160-3167
Keywords: "Diversity-oriented synthesis"

134 Haitham  Hassan , Steve  Marsden and Adam  Nelson , "Design and synthesis of a fragment set based on twisted bicyclic lactams", Bioorg. Med. Chem. Lett. 2018, 26, 3030-3033
Keywords: "Diversity-oriented synthesis"

133 Anthony  Aimon , Ian  Churcher, Patrick  Collins, Philip  Craven , Richard  Doveston , Daniel  Foley , Steve  Marsden , Adam  Nelson , Romain  Talon and Frank  von Delft, "Synthesis and Demonstration of the Biological Relevance of sp3-rich Scaffolds Distantly Related to Natural Product Frameworks", Chem. Eur. J. 2017, 23, 15227-15232
Keywords: "Diversity-oriented synthesis"

132 Will  Farnaby, Joan  Mayol Llinas and Adam  Nelson , "Modular synthesis of thirty lead-like scaffolds suitable for CNS drug discovery", Chem. Commun. 2017, 53, 12345-12348
Keywords: "Diversity-oriented synthesis"

129 Katherine  Abrahams, Del  Besra, Mark  Dow , Adam  Nelson , Luis  Vaz and Stuart  Warriner , "Modular Synthesis of Diverse Natural Product-like Macrocycles: Discovery of Hits with Antimycobacterial Activity", Chem. Eur. J. 2017, 23, 7207-7211
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

128 Shiao  Chow and Adam  Nelson , "Embarking on a Chemical Space Odyssey", J. Med. Chem. 2017, 60, 3591-3593
Keywords: "Diversity-oriented synthesis"

126 Andy  Ayscough, Will  Farnaby, Joan  Mayol Llinas and Adam  Nelson , "Assessing molecular scaffolds for CNS drug discovery", Drug Discov. Today 2017, 22, 965-969
Keywords: "Diversity-oriented synthesis"

1 Anthony  Aimon , Patrick  Collins, Philip  Craven , Richard  Doveston , Daniel  Foley , Steve  Marsden , Adam  Nelson , Romain  Talon and Frank  von Delft, "Synthesis and Demonstration of the Biological Relevance of sp3-rich Scaffolds Distantly Related to Natural Product Frameworks", Chemistry - A European Journal 2017, 23, 15227–15232
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

124 Daniel  Foley , Steve  Marsden and Adam  Nelson , "Evaluating New Chemistry to Drive Molecular Discovery: Fit for Purpose?", Angew. Chem. Int Ed. 2016, 55, 13650-13657
Keywords: "Diversity-oriented synthesis"

123 Philip  Craven , James  Firth , Matthew  Lilburn, Steve  Marsden , Adam  Nelson and Axel  Pahl, "A Biosynthesis-Inspired Approach to over Twenty Diverse Natural Product-Like Scaffolds", Chem. Commun. 2016, 52, 9837-9840
Keywords: "Diversity-oriented synthesis"

122 Ian  Churcher, Ignacio  Colomer Utrera , Philip  Craven , Richard  Doveston , Christopher  Empson, Steve  Marsden , Adam  Nelson and Zach  Owen, "A divergent synthetic approach to diverse molecular scaffolds: assessment of lead-likeness using LLAMA, an open access computational tool", Chem. Commun. 2016, 52, 5209-5212
Keywords: "Diversity-oriented synthesis"

116 Anthony  Aimon , Mark  Dow , George  Karageorgis , Adam  Nelson and Stuart  Warriner , "Activity-directed Synthesis with Intermolecular Reactions: Development of a Fragment into a Range of Androgen Receptor Agonists", Angew. Chem. Int. Ed. 2015, 54, 13538-13544
Keywords: "Diversity-oriented synthesis"

115 Jorg  Benningshof, Fabrizio  Giordanetto, Daniel  Hamza, Tuomo  Kalliokoski, Anna  Karawajczyk, Remy  Morgantin , Gerhard  Muller, Adam  Nelson , Alex  Piochet, Kees  Pouwer and Dimitrios  Tzalis, "Expansion of chemical space for collaborative lead generation and drug discovery: the European Lead Factory perspective", Drug Discov. Today 2015, , in press
Keywords: "Diversity-oriented synthesis"

114 James  Firth , Richard  Foster , Rachel  Guilleux, Tuomo  Kalliokoski, Steve  Marsden , Remy  Morgantin , Adam  Nelson , Stuart  Warriner and Rong  Zhang , "Exploitation of the Ugi-Joullié reaction in the synthesis of libraries of drug-like bicyclic hydantoins", Synthesis 2015, , 2391-2406
Keywords: "Diversity-oriented synthesis"

112 Ian  Churcher, Richard  Doveston , Daniel  Foley , Steve  Marsden and Adam  Nelson , "A systematic approach to diverse, lead-like scaffolds from alpha,alpha-disubstituted amine acids", Chem. Commun. 2015, 51, 11174-11177
Keywords: "Diversity-oriented synthesis"

111 Adam  Nelson and Didier  Roche, "Innovative Approaches to the Design and Synthesis of Small Molecule Libraries", Bioorg. Med. Chem. 2015, 23, 2613
Keywords: "Diversity-oriented synthesis"

110 Ololade  Adeniji, George   Burslem , Ignacio  Colomer Utrera , Philip  Craven , Richard  Foster , Tuomo  Kalliokoski, Steve  Marsden , Adam  Nelson , Martin  Rasmussen and Anthony  Willaume, "Aminomethylhydroxylation of alkenes: Exploitation in the synthesis of scaffolds for small molecule libraries", Bioorg. Med. Chem. 2015, , in press
Keywords: "Diversity-oriented synthesis"

109 Anthony  Aimon , Philip  Craven , Mark  Dow , Nicolas  Fleury-Bregeot, Richard  Foster , Rachel  Guilleux, Tuomo  Kalliokoski, Steve  Marsden , Remy  Morgantin , Adam  Nelson and Didier  Roche , "Design, synthesis and decoration of molecular scaffolds for exploitation in the production of alkaloid-like libraries", Bioorg. Med. Chem. 2015, , doi:10.1016/j.bmc.2014.12.048
Keywords: "Diversity-oriented synthesis"

108 Amanda  Campbell , Ian  Churcher, Richard  Doveston , Mark  Dow , Daniel  Foley , David  House , Ho Yin (John)  Li , Steve  Marsden , Adam  Nelson and Paolo  Tosatti , "A unified lead-oriented synthesis of over fifty molecular scaffolds", Org. Biomol. Chem. 2015, 13, 859-865
Keywords: "Diversity-oriented synthesis"

107 George  Karageorgis , Adam  Nelson and Stuart  Warriner , "Efficient discovery of bioactive scaffolds by activity-directed synthesis", Nature Chem. 2014, 6, 872-876
Keywords: "Diversity-oriented synthesis"

106 Amanda  Campbell , Joachim  Horn , David  House , Ho Yin (John)  Li , Steve  Marsden and Adam  Nelson , "A convergent rhodium-catalysed asymmetric synthesis of tetrahydroquinolines", Chem. Commun. 2014, 50, 10222-10224
Keywords: "Diversity-oriented synthesis"

104 George   Burslem , Andrew  Grant , Tom   James , Paul  MacLellan , Adam  Nelson , Iain  Simpson , Sri  Sridharan and Stuart  Warriner , "A modular lead-oriented synthesis of diverse piperazine, 1,4-diazepane and 1,5-diazocane scaffolds", Org. Biomol. Chem. 2014, 12, 2584-2591
Keywords: "Diversity-oriented synthesis"

100 Andrew  Grant , Tom   James , Adam  Nelson , Iain  Simpson and Sri  Sridharan , "Modular, gold-catalysed approach to the synthesis of lead-like piperazine scaffolds", Org. Lett. 2013, 15, 6094-6097
Keywords: "Diversity-oriented synthesis"

99 Ramkrishna  Basak , Martin  Fisher , Colin  Fishwick , Arnout  Kalverda , Adam  Nelson and Bruce  Turnbull, "Discovery of novel FabF ligands inspired by platensimycin by integrating structure-based design with diversity-oriented synthetic accessibility", Org. Biomol. Chem. 2014, 12, 486-494
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

98 Richard  Doveston , Steve  Marsden and Adam  Nelson , "Towards the realisation of lead-oriented synthesis", Drug Discov. Today 2014, 7, 813-819
Keywords: "Diversity-oriented synthesis"

96 Mark  Dow , Sushil  Maurya , Adam  Nelson and Stuart  Warriner , "Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks", Beil. J. Org. Chem. 2013, 9, 775-785
Keywords: "Diversity-oriented synthesis"

95 Mark  Dow , Francesco  Marchetti and Adam  Nelson , "Diversity-oriented synthesis of natural product-like libraries", Diversity-oriented synthesis, ed. A. Trabocchi 2013, , chapter 9, pp 291-323
Keywords: "Diversity-oriented synthesis"

94 Paul  MacLellan and Adam  Nelson , "A conceptual framework for analysing and planning synthetic approaches to diverse lead-like scaffolds", Chem. Commun. 2013, , 2383-2393
Keywords: "Diversity-oriented synthesis"

89 Mark  Dow , Martin  Fisher , Tom   James , Francesco  Marchetti and Adam  Nelson , "Towards the systematic exploration of chemical space", Org. Biol. Chem. 2012, , in press
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

88 Amanda  Campbell , David  House , Steve  Marsden , Adam  Nelson and Paolo  Tosatti , "Control in Sequential Asymmetric Allylic Substitution: Stereodivergent Access to N,N-Diprotected Unnatural Amino Acids", J. Org. Chem. 2011, 76, 5495-5501
Keywords: "Diversity-oriented synthesis"

86 Christian  Einzinger , Sushil  Maurya , Ben  McKeever-Abbas , Sarah  Murrison and Adam  Nelson , "Synthesis of Skeletally-Diverse Alkloid-like Small Molecules", Eur. J. Org. Chem. 2011, , 2354-2359
Keywords: "Diversity-oriented synthesis"

85 Martin  Fisher and Adam  Nelson , "The Chemical Genetic Approach: The Interrogation of Biological Mechanisms with Small Molecule Probes", New Frontiers in Chemical Biology: Enabling Drug Discovery, ed. M. E. Bunnage 2011,
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

84 Amanda  Campbell , Joachim  Horn , David  House , Adam  Nelson and Paolo  Tosatti , "Iridium-Catalyzed Asymmetric Allylic Amination with Polar Amines: Access to Building Blocks with Lead-Like Molecular Properties", Adv. Synth. Cat. 2010, 352, 3153-3157
Keywords: "Diversity-oriented synthesis"

81 Jerome  Hayes, Tom   James , Tom  Lanyon-Hogg , Stuart  Leach , Adam  Nelson , Catherine  O'Leary-Steele and Palle  Pedersen , "Synthesis of Small Molecules with High Scaffold Diversity: Exploitation of Metathesis Cascades in Combination with Inter- and Intramolecular Diels-Alder Reactions", Chem. Eur. J. 2010, , 9563-9671
Keywords: "Diversity-oriented synthesis"

79 Amanda  Campbell , Joachim  Horn , David  House , Ho Yin (John)  Li , Steve  Marsden , Adam  Nelson , Rachel  Shearer and Gordon  Weingarten , "Convergent synthesis of dihydroquinolones from o-aminoarylboronates", Tetrahedron 2009, 65, 9002-9007
Keywords: "Diversity-oriented synthesis"

77 Chris  Cordier , Jerome  Hayes, Adam  Nelson , Catherine  O'Leary-Steele and Stuart  Warriner , "A fluorous-tagged Safety Catch Linker for Preparing Heterocycles by Ring-Closing Metathesis", Org. Lett. 2009, 11, 915-918
Keywords: "Diversity-oriented synthesis"

76 Steve  Bartlett , Christian  Einzinger , David  Glowacki , Ben  McKeever-Abbas , Sarah  Murrison , Adam  Nelson , James  Titchmarsh and Stuart  Warriner , "Remarkably slow rotation about a single bond between an sp3-hybridised carbon and an aromatic ring without ortho substituents", Chem. Eur. J. 2009, 15, 2185-2189
Keywords: "Diversity-oriented synthesis"

74 Chris  Cordier , Stuart  Leach , Daniel  Morton , Adam  Nelson and Stuart  Warriner , "Synthesis of natural product-like molecules with over eighty distinct skeletons", Angew. Chemie. Int. Ed. 2009, 48, 104-109
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

72 Joachim  Horn , David  House , Steve  Marsden , Adam  Nelson and Gordon  Weingarten , "Convergent, Regiospecific Synthesis of Quinolines from o-Aminophenylboronates ", Org. Lett. 2008, 10, 4117-4120
Keywords: "Diversity-oriented synthesis"

71 Chris  Cordier , Stuart  Leach , Daniel  Morton , Adam  Nelson , Catherine  O'Leary-Steele , Stuart  Warriner and Thomas  Woodhall , "An efficient method for synthesising unsymmetrical silaketals: substrates for ring-closing, including macrocycle-closing, metathesis", Org. Biomol. Chem. 2008, 6, 1734-1737
Keywords: "Diversity-oriented synthesis"

70 Chris  Cordier , Daniel  Morton , Sarah  Murrison , Adam  Nelson and Catherine  O'Leary-Steele , "Natural products as an inspiration in the diversity-oriented synthesis of bioactive compound libraries", Nat. Prod. Rep. 2008, , 719-737
Keywords: "Chemical Genetics" "Diversity-oriented synthesis"

69 Chris  Cordier , Stuart  Leach , Gordon  McKiernan , Daniel  Morton , Adam  Nelson and Stuart  Warriner , "A fluorous-tagged linker from which small molecules are released by ring-closing metathesis", J. Org. Chem. 2008, 73, 2752-2759
Keywords: "Diversity-oriented synthesis"

People currently working in this research area:

Sergio Celis

Richard Foster

Daniel Francis

George Karageorgis

Bobby Lowe

Steve Marsden

Adam Nelson

Ephraim Okolo

Scott Rice

Aisha Syed

Chloe Townley

Stuart Warriner

Nicholas Westwood

Jack White