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TITLE & ABSTRACT of talk - Prof John Joule
Title:
Heterocyclic Chemistry – Reactivity and Synthesis
Abstract
The 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]
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.
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.