Research

Stereochemically diverse libraries

The complete control of the configuration of libraries of stereoisomers

The complete control of stereochemistry - that is, the ability to synthesise any stereoisomer at will - is a challenging goal for the synthetic chemist.  We have developed a wide range of complementary methods for preparing libraries of stereochemically diverse libraries of small molecules.  In particular, we have focussed on the synthesis of libraries of stereochemically diverse sugar mimetics such as C-substituted monosaccharides, C-linked disaccharide analogues, aza-C-linked disaccharide mimetics, sialic acid mimetics and aminoglycoside analogues.  Where possible, we have tried to exploit the hidden symmetry of our target molecules.  We have shown, for example that even unsymmetrical disaccharide mimetics may be prepared using a two-directional approach, which greatly reduces the number of synthetic steps required.

Publications in this area:

91 Steve  Marsden , Adam  Nelson and Paolo  Tosatti , "Recent advances and applications of iridium-catalysed asymmetric allylic substitution", Org. Biomol. Chem 2012, 10, 3157-3163
Keywords: "Stereochemically diverse libraries"

63 Chris  Adams, Alison  Ashcroft, Andy  Baron, Blandine  Clique , Alan  Ironmonger , Adam  Nelson , Peter  Stockley and Ben  Whittaker , "Scanning conformational space with a library of stereo- and regiochemically diverse aminoglycoside derivatives: The discovery of new ligands for RNA hairpin sequences", Org. Biomol. Chem. 2007, 5, 1081-1086
Open Access Version
Keywords: "Stereochemically diverse libraries" "Chemical Genetics"

61 Alan  Berry , Lorna  Farnsworth , Adam  Nelson , Gavin  Williams and Thomas  Woodhall , "Creation of a Pair of Stereochemically Complementary Biocatalysts", J. Am. Chem. Soc. 2006, 128, 16238-16247
Keywords: "Stereochemically diverse libraries" "Directed evolution"

55 Alex  Bullock, J. E.  Debreczeni, O. Y.  Fedorov, Stefan  Knapp, Brian  Marsden and Adam  Nelson , "Structural Basis of Inhibitor Specificity of the Human Protooncogene Proviral Insertion Site in Moloney Murine Leukemia Virus (PIM-1) Kinase", J. Med. Chem. 2005, 48, 7604-7614
Keywords: "Stereochemically diverse libraries" "Chemical Genetics"

54 Simon  Barrett , Steve  Bartlett , Amanda  Bolt , Alan  Ironmonger , Catherine  Joce , Adam  Nelson and Thomas  Woodhall , "Configurational stability of bisindolylmaleimide cyclophanes: From conformers to the first configurationally stable, atropisomeric bisindolylmaleimides", Chem. Eur. J. 2005, 11, 6277-6285
Open Access Version
Keywords: "Stereochemically diverse libraries"

53 Andrew  Kennedy , Adam  Nelson and Alexis  Perry , "Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives", Beilstein J. Org. Chem. 2005, 1, 2
Keywords: "Stereochemically diverse libraries" "New strategies for asymmetric synthesis"

52 Steve  Bartlett , Godfrey  Beddard, Richard  Jackson, Veysel  Kayser, Colin  Kilner , Andrew  Leach, Adam  Nelson , Peter  Oledzki, Peter  Parker, Gavin  Reid and Stuart  Warriner , "Comparison of the ATP binding sites of Protein Kinases using conformationally diverse bisindolylmaleimides", J. Am. Chem. Soc. 2005, 127, 11699-11708
Keywords: "Stereochemically diverse libraries" "Chemical Genetics"

51 Alan  Berry , Adam  Nelson , Gavin  Williams and Thomas  Woodhall , "Structure-guided saturation mutagenesis of N-acetylneuraminic acid lyase for the synthesis sialic acid mimetics", Prot. Eng. Des. Sel. 2005, 18, 239-246
Keywords: "Stereochemically diverse libraries" "Directed evolution"

50 Blandine  Clique , Jackie  Colley , Alan  Ironmonger , Adam  Nelson , Peter  Stockley, James  Titchmarsh and Ben  Whittaker , "Synthesis of a library of stereo- and regiochemically diverse aminoglycoside derivatives", Org. Biomol. Chem. 2005, 3, 2776-2785
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries" "Chemical Genetics"

49 Alan  Berry , Adam  Nelson , Gavin  Williams and Thomas  Woodhall , "Creation of an aldolase for the parallel synthesis of sialic acid mimetics", Angew. Chem., Int. Ed. 2005, 44, 2109-2112
Open Access Version
Keywords: "Stereochemically diverse libraries" "Directed evolution"

47 Andrew  Kennedy , Adam  Nelson and Alexis  Perry , "A general, two-directional synthesis of aza-(1 to 1)-C-disaccharide mimetics", Chem. Commun. 2005, , 1646-1648
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries"

46 Alan  Berry , Adam  Nelson , Gavin  Williams and Thomas  Woodhall , "Synthesis of screening substrates for the directed evolution of sialic acid aldolase: Towards tailored enzymes for the preparation of influenza A sialidase inhibitor analogues", Org. Biomol. Chem. 2005, 3, 1795-1800
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries" "Directed evolution"

42 Adam  Nelson , "The development of strategies and methods for the synthesis of biologically active compounds", New J. Chem. 2004, 28, 771-776
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries" "New strategies for asymmetric synthesis" "Natural product synthesis"

41 Andrew  Kennedy , Adam  Nelson and Alexis  Perry , "Highly diastereoselective addition of ketone enolates to N-sulfinyl imines: Asymmetric synthesis of syn- and anti-1,3-amino alcohol derivatives", Synlett 2004, , 967-970
Keywords: "Stereochemically diverse libraries"

40 Steve  Bartlett and Adam  Nelson , "Evaluation of alternative approaches for the synthesis of macrocyclic bisindolylmaleimides", Org. Biomol. Chem. 2004, 2, 2874-2883
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries"

39 Steve  Bartlett and Adam  Nelson , "Towards configurationally stable bisindolylmaleimide cyclophanes: Potential tools for investigating protein kinase function", Chem. Commun. 2004, , 1112-1113
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries" "Chemical Genetics"

31 Steve  Bartlett , Robert  Hodgson , Joanne  Holland , Matthew  Jones , Colin  Kilner , Adam  Nelson and Stuart  Warriner , "Exploiting predisposition in the stereoselective synthesis of mono-, bi- and tetracyclic oxygen heterocycles: Equilibration between, and trapping of, alternative di- and tetraacetals", Org. Biomol. Chem. 2003, 1, 2393-2402
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries" "New strategies for asymmetric synthesis"

29 Michael  Harding , Robert  Hodgson , Tahir  Majid , Kenny  McDowall and Adam  Nelson , "A stereodivergent, two-directional synthesis of stereoisomeric C-linked disaccharide mimetics", Org. Biomol. Chem. 2003, 1, 338-349
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries" "New strategies for asymmetric synthesis"

27 Robert  Hodgson , Tahir  Majid and Adam  Nelson , "Desymmetrisation of meso difuryl alcohols, diols and their derivatives: complementary directed and undirected asymmetric dihydroxylation reactions", J. Chem. Soc., Perkin Trans. 1 2002, , 1631-1643
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries" "New strategies for asymmetric synthesis"

26 Robert  Hodgson , Tahir  Majid and Adam  Nelson , "Towards complete stereochemical control: complementary methods for the synthesis of six diastereoisomeric monosaccharide mimetics", J. Chem. Soc., Perkin Trans. 1 2002, , 1444-1454
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries"

23 Robert  Hodgson , Tahir  Majid and Adam  Nelson , "Directed and undirected asymmetric dihydroxylation reactions: application in the synthesis of a C-linked analogue of allolactose", Chem. Commun. 2001, , 2076-2077
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries"

20 Michael  Harding and Adam  Nelson , "A general, two-directional synthesis of C-(1 to 6)-linked carbohydrate mimetics: synthesis from non-carbohydrate-based starting materials", Chem. Commun. 2001, , 695-696
Open Access Version - provided courtesy of the RSC
Keywords: "Stereochemically diverse libraries"

People currently working in this research area:

George Karageorgis

Steve Marsden

Adam Nelson

Chloe Townley