The Need for a Unified Structural Theory of Constitutional Chemistry

A chemical synthesis of a target molecule could be described in terms of the empirical formulas of the starting materials and some representative intermediates which are characteristic of the conversion of the starting materials into the synthetic target. Such a description would, however, be useless for most synthetic purposes, because it would be representative of a too-large equivalence class of syntheses. Perkins attempt to synthetize quinine from aniline, which led to the discovery of the triphenyl methane dyes, is a well documented example for the need of defining and representing equivalence classes of syntheses in a more detailed manner than by some characteristic empirical formulas. 

The number of conceivable synthetic pathways is reduced substantially if we confine the term synthesis to those reasonable sequences of chemical reactions which lead from some readily available starting materials to the desired target compounds without obvious waste of material and labor, and without involving nonsense sequences of operations, i. e., synthetic pathways that contain imnecessary loops . ) For instance, we should not consider a synthesis of NaCl from strychnine hydrochloride and tri-phenylmethyl sodium i ) a reasonable synthetic of NaCl. 

Already in the mid-sixties, the model experiments for peptide syntheses by stereoselective four component condensations demonstrated the potential usefulness of artificial intelligence for the solution of s)mthetic problems. The optimum reaction conditions for the stereoselective synthesis of a given four component condensation product can be found only with some rather detailed knowledge of the very complex reaction mechanism of four component condensations. The latter could be elucidated only with the aid 

This led further to preliminary computer assisted planning study of the synthesis of a variety of proteins, such as the A chain of insulin, by a combination of conventional peptide synthetic methods and stereoselective four component condensations which revealed that, for the latter, there are approximately 139,000,000 syntheses of the above-mentioned type, differing widely with respect to yield expectations andnumber of required steps. 12) Although it would be beyond the capabilities of the presently available advanced computers to generate and compare all of these conceivable pathways according to suitable criteria, it took only a few minutes of computing 

The design of a general S5mthetic design program which is not confined to certain classes of compounds, and is capable of taking into account unprecedented, but conceivable, chemistry, requires a unified mathematical theory of constitutional chemistry on the basis of a few general principles. 

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