MARINE ALKALOIDS

 

The study of the structures of plant alkaloids dates back to the very beginnings of Organic Chemistry - quinine was isolated in pure form in 1817 and morphine 10 years before that.

 

Oceans cover 70% of the earth's surface and contain 95% of the biosphere.

 

More than 95% of all animals are invertebrates.

 

 

The marine environment has given rise to unique biological and chemical evolution, very different from land-based life.

 

 

Over the last quarter of a century it has been possible to study nitrogenous substances isolated from marine animals - we can call them 'marine alkaloids'. Just as the interest in quinine and morphine was encouraged by the use of such substances in medicine, so it has been shown that many marine alkaloids have biological properties which may prove to be of value to mankind.

Invertebrates such as sponges, soft corals, molluscs, coelenterates, and ascidians produce secondary metabolites of unprecedented structures; sponges and ascidians, in particular, produce nitrogen-containing substances.

Most natural products from the oceans are structurally novel and in addition, many possess potent biological activities. Full biological evaluations of such substances are however severely hampered by the difficulty of obtaining substantial quantities - it is difficult, and indeed ecologically undesirable, to harvest large quantities of the marine creatures from which they are isolated; it is also difficult to grow such animals in the laboratory.

Access to substantial quantities of these novel substances must then be by way of chemical synthesis, which also has the very considerable additional advantage that it, and only it allows analogues to be prepared and thus desirable biological activities to be maximised and any undesirable side-effects minimised - the natural substance is, in the jargon of pharmaceutical industry, a 'lead compound'.

We have been engaged for some time on the development of synthetic routes to several classes of marine alkaloids, including pyrrolo[4,3,2-de]quinolines, pyrido[3´,2´:4,5]pyrrolo[1,2-c]pyrimidines, pyrrolo [2,3,4-kl] acridines, and pyrido[2,3,4-kl]acridines. In some of this work we collaborate with the group of Dr. Mercedes Alvarez in the Laboratori de Química Orgànica, Facultat de Farmàcia, University of Barcelona, Spain, facilitated by exchanges of personnel in both Northerly and Southerly directions.