Prof Stephen Caddick - Organic Chemistry and Chemical Biology

Chemical Biology Organic Synthesis Catalysis Synthetic Methodology Diversity Oriented Synthesis Protein Ligand Interactions Structure based design Medicinal chemistry

Publications list tel: +44 (0)20 7679 7482 fax: +44 (0)20 7679 4603 internal: 27482 email: s.caddick@ucl.ac.uk Biographical Details

Research is focused in three main areas

• Chemical Biology and Medicinal Chemistry
• Organometallic Chemistry and Catalysis
• Synthetic Methodology and Natural Product Synthesis

Chemical Biology and Medicinal Chemistry

Our interests in this area include: (a) Studies on protein-ligand complexes of the natural product Neocarzinostatin (D. N. Woolfson, Chemistry & Biochemistry, Bristol); (b) Functional studies on human and bacterial methylarginine processing enzymes (Leiper, Singer, UCL, Medicine & Intensive Care); (c) Studies on the mechanism of nuclear transport of HIV (with Fassati, UCL Virology); (d) Development of novel NMDA receptor ligands (with Kullmann, UCL Inst. of Neurology); (e) Studies on beta-receptor antagonists (with Tinker, UCL Medicine & J. Black, KCL); (f) Treatment of septic shock (with Leiper, Singer).

Organometallic Chemistry and Catalysis

With Prof F. G. Cloke at Sussex we have a long-standing programme directed toward development of methods for the generation of new NHC-M complexes and studying their mechanism of activity. We discovered the first class of two coordinate Pd-NHC complex, demonstrated its effectiveness in a wide range of catalytic processes. We also have collaborative links with Gois and Afonso in Portugal on the generation and activity of rhodium-NHC complexes and with Lewis (UCL) on Ni and Fe-NHC complexes. Our combined structural, mechanistic and organic synthesis approach has been productive (12 papers) and the publications well-cited.

Synthetic Methodology and Natural Product Synthesis

The research group has a strong interest in the development of new methods for natural product synthesis and synthetic methodology and recent / ongoing work includes: (a) Development of new methods for amino-acids using Dynamic Kinetic Resolution; (b) Development of new methods for sulfonamide synthesis; (c) Development of methods for Diversity-oriented synthesis for Chemical Biology and Medicinal Chemistry; (d) Synthesis of natural and non-natural enediynes; (e) Development of Novel Free-Radical Methods for Organic Synthesis

Selected Publications

1. Thominet O, Baker JR, Britton H, Etheridge ZC, Soscia MG, Caddick S.
   Synthetic strategies to epoxydiynes and a key synthon of the neocarzinostatin chromophore.
   Org Biomol Chem. 2007 Nov 21;5(22):3703-12. Epub 2007 Oct 3.
2. Gois PM, Trindade AF, Veiros LF, André V, Duarte MT, Afonso CA, Caddick S, Cloke FG.
   Tuning the reactivity of dirhodium(II) complexes with axial N-heterocyclic carbene ligands: the arylation of aldehydes.
   Angew Chem Int Ed Engl. 2007;46(30):5750-3.
3. Baker JR, Woolfson DN, Muskett FW, Stoneman RG, Urbaniak MD, Caddick S.
   Protein-small molecule interactions in neocarzinostatin, the prototypical enediyne chromoprotein antibiotic.
   Chembiochem. 2007 May 7;8(7):704-17.
4. Morris T, Sandham D, Caddick S.
   A microwave enhanced cross-metathesis approach to peptidomimetics.
   Org Biomol Chem. 2007 Apr 7;5(7):1025-7. Epub 2007 Feb 5.
5. Esposito O, Lewis AK, Hitchcock PB, Caddick S, Cloke FG.
   Synthesis and reactivity of alkyl-palladium N-heterocyclic carbene complexes.
   Chem Commun (Camb). 2007 Mar 12;(11):1157-9. Epub 2007 Feb 14.
6. Fitzmaurice RJ, Etheridge ZC, Jumel E, Woolfson DN, Caddick S.
   Microwave enhanced palladium catalysed coupling reactions: a diversity-oriented synthesis approach to functionalised flavones.
   Chem Commun (Camb). 2006 Dec 14;(46):4814-6.
7. Wilden JD, Geldeard L, Lee CC, Judd DB, Caddick S.
   Trichlorophenol (TCP) sulfonate esters: a selective alternative to pentafluorophenol (PFP) esters and sulfonyl chlorides for the preparation of sulfonamides.
   Chem Commun (Camb). 2007 Mar 14;(10):1074-6. Epub 2006 Dec 21.
8. Baker JR, Thominet O, Britton H, Caddick S.
   An efficient synthesis of epoxydiynes and a key fragment of neocarzinostatin chromophore.
   Org Lett. 2007 Jan 4;9(1):45-8.
9. Lewis AK, Mok BJ, Tocher DA, Wilden JD, Caddick S.
   New synthesis of beta-sultams from pentafluorophenyl sulfonates.
   Org Lett. 2006 Nov 23;8(24):5513-5.
10. Caddick S.
    Wiki and other ways to share learning online.
    Nature. 2006 Aug 17;442(7104):744.
11. Caddick S, Muskett FW, Stoneman RG, Woolfson DN.
    Synthetic ligands for apo-neocarzinostatin.
    J Am Chem Soc. 2006 Apr 5;128(13):4204-5.
12. Vallance P, Bush HD, Mok BJ, Hurtado-Guerrero R, Gill H, Rossiter S, Wilden JD, Caddick S.
    Inhibition of dimethylarginine dimethylaminohydrolase (DDAH) and arginine deiminase (ADI) by pentafluorophenyl (PFP) sulfonates.
    Chem Commun (Camb). 2005 Nov 28;(44):5563-5. Epub 2005 Oct 11.
13. Caddick S, Wilden JD, Judd DB.
    Observations on the reactivity of pentafluorophenyl sulfonate esters.
    Chem Commun (Camb). 2005 Jun 7;(21):2727-8. Epub 2005 Apr 15.
14. Treweeke NR, Hitchcock PB, Pardoe DA, Caddick S.
    Controlling diastereoselectivity in the reactions of enantiomerically pure alpha-bromoacyl-imidazolidinones with nitrogen nucleophiles: substitution reactions with retention or inversion of configuration.
    Chem Commun (Camb). 2005 Apr 14;(14):1868-70. Epub 2005 Feb 8.
15. Caddick S, Cloke FG, Hitchcock PB, de K Lewis AK.
    Unusual reactivity of a nickel N-heterocyclic carbene complex: tert-butyl group cleavage and silicone grease activation.
    Angew Chem Int Ed Engl. 2004 Nov 5;43(43):5824-7.
16. Urbaniak MD, Bingham JP, Hartley JA, Woolfson DN, Caddick S.
    Design and synthesis of a nitrogen mustard derivative stabilized by apo-neocarzinostatin.
    J Med Chem. 2004 Sep 9;47(19):4710-5.
17. McCarroll AJ, Sandham DA, Titcomb LR, Lewis AK, Cloke FG, Davies BP, de Santana AP, Hiller W, Caddick S.
    Studies on high-temperature amination reactions of aromatic chlorides using discrete palladium-N-heterocyclic carbene (NHC) complexes and in situ palladium/imidazolium salt protocols.
    Mol Divers. 2003;7(2-4):115-23.

Short Overview of Caddick Group Research

The Caddick group carries out synthetic work to: (a) Develop new methods, and strategies for target and diversity oriented synthesis; (b) To develop molecules for utilisation as probes, diagnostic tools or as therapeutics. The research group is specifically engaged in synthetic methodology in areas such as free-radical chemistry, organometallic chemistry; sulphonamide synthes11 September, 2008inal interest include (a) Studies on protein-ligand complexes of the natural product Neocarzinostatin; (b) Functional studies on human and bacterial methylarginine processing enzymes; (c) Studies on the mechanism of nuclear transport of HIV; (d) Development of novel NMDA receptor ligands; (e) Studies on beta-receptor antagonists; (f) Treatment of septic shock

This page last modified 24 February, 2010