Centre for Molecular and Biomolecular Informatics
Radboud University Nijmegen
|Analysis of Complex Synthetic Problems|
The total synthesis of structurally complex compounds is a challenging undertaking, in intellectual as well as practical respects. Whereas simple compounds can usually be made by synthesis routes comprising a few reaction steps (say two to five), complicated molecules may require a lengthy sequence of reactions, not seldom more than twenty. Most such multi-step syntheses are executed, or at least attempted, according to a plan designed beforehand on paper or blackboard. How do chemists arrive at such synthetic plans? Traditionally, synthesis design was based upon associative thinking processes, the most important of which were:
The last of these represents an attempt to reduce the complexity of the design problem, but the selection of a suitable intermediary structure is still a highly intuitive process. The associative approach to synthesis design becomes less opportune as the complexity of the problem, and hence the number of steps required, increases.
These structures, made by total synthesis during the past century, illustrate the ever-increasing complexity of the synthesis tasks that chemists have imposed upon themselves, each success prompting an even more challenging undertaking. None of the targets above give obvious handholds for synthesis design by association; each of their syntheses was a `first' and neither starting materials nor promising intermediary structures stand out. A more systematic and generally applicable problem-solving technique is clearly called for, and is presented by retrosynthetic analysis.
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|Page author: Martin Ott||Last update: Wednesday, 1 September 2004|