Prof John Joule

 

Title: Heterocyclic Chemistry – Reactivity and Synthesis

Abstract

he reactivity and synthesis of heterocyclic substances pervades all aspects of organic chemistry – it has been estimated that more than half of all published work concerns one aspect or another of heterocyclic chemistry. Many secondary metabolites possess intriguing, polycyclic heterocyclic frameworks.[1] The vast majority of medicines are heterocyclic ‘small’ molecules, or contain heterocyclic sub-units.[2] A detailed knowledge and understanding of heterocyclic principles and synthesis[3] is clearly essential, then, for the pursuance of medicinal chemistry. This lecture describes two academic investigations, spanning Manchester, Barcelona, and Mauritius, which show how heterocyclic understanding can be put to use in the construction of complex structures.

 

The alkaloid apparicine 1, biosynthetically significant as the first indole alkaloid lacking the tryptophan-derived ethanamine side-chain, has been synthesized from 1-phenylsulfonylindole 2 in eight steps in both Manchester and Barcelona, but using completely different strategies.[4,5]

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The 1,3-dipolar cycloaddition of pyrazinium-3-olates to dipolarophiles can be utilized to construct the carbon skeleton of the anti-tumour antibiotic quinocarcin.[6] More detailed study of such cycloadditions in Manchester and Mauritius has suggested that the previously accepted mechanism may be wrong – this will be discussed.

 

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References

[1]  See for example ‘The Alkaloids; Chemistry and Biology’, Volumes 1–69, 1950-2009, Elsevier.

[2]  See for example ‘Comprehensive Medicinal Chemistry II’, D. Triggle and J. Taylor, (Eds),

     Elsevier, 2006; ‘Molecules and Medicine’, E. J. Corey, B. Czakó, and L. Kürti, Wiley, 2007.

[3]  ‘Heterocyclic Chemistry’, J. A. Joule and K. Mills, Wiley, 2010, 690 pp.

[4]  M.-L. Bennasar, E. Zulaica, D. Solé, and S. Alonso, Chem. Commun., 2009, 3372-3374.

[5]  J. Kettle, P. Allway, D. Roberts, and J. A. Joule, Heterocycles, 2010, 82, in press.

[6]  D. A. Peters, N. D. Yates, D. I. C. Scopes, and J. A. Joule, Heterocycles, 1995, 40, 983-991.