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WYKŁADY PLENARNE I ZAPROSZONE

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FIFTY YEARS OF HETEROCYCLIC CHEMISTRY AT MANCHESTER UNIVERSITY

John A. Joule

School of Chemistry, The University of Manchester, UK

This lecture will tracę my career from North Wales to Manchester, then to Princeton and Stanford in the USA, and back to Manchester. Various aspects of Heterocyclic

Chemistry¹ will be illustrated,

extracted from my research from 1961.

Early studies involved isolation and structure

determination of indole alkaloids: pseudakuammigine from the West African tree Picralima nitida; then ellipticine, uleine and congeners, and apparicine from various Brazilian Aspidosperma species, working with Carl Djerassi in Stanford.

Synthetic studies on lycorane-related compounds working with Richard K. Hill in Princeton were based on Diels-Alder chemistry.

Our total synthesis of apparicine depended on Mannich chemistry to form the eight-membered ring.

There are in excess of forty molybdenum and tungsten enzymes, occurring throughout the entire rangę of organisms in the biosphere, that catalyse oxygen atom transfer. They all have the same cofactor, known as

The concept that an enamine (conjugated) is morę stable than its isomeric allylamine was central to our synthesis of uleine.

molybdopterin, that coordinates the metal centre. We synthesized the cofactor, a pteridine derivative, in protected form.

Our total synthesis of ellipticine, a potent antineoplastic agent, allows the preparation of analogues by proceeding through ellipticine quinone.

3-Oxidopyraziniums act as 1,3-dipoles and undergo cycloadditions generating 3,8-diazabicyclo[3.2.1]octanes.

11 ] 'Heterocyclic Chemistry', 1“ Edition, J. A. Joule & G. F. Smith, Van Nostrand Reinhold Co., 1972; 5'" Edition, J. A. Joule & K. Mills, Wiley, 2010. 'Heterocyclic Chemistiv at a Glance'. 2^nd Edition, J. A. Joule & K. Mills, Wiley, 2013.

Initial attempts to synthesise apparicine were unsuccessful but led to the discovery of indole (5-nucleophilic substitution processes, which proved to be generał for the construction of a variety of fused indoles.