Planning Organic Syntheses

The purpose of this research was to explore the representation, manipulation, and utilization of strategic knowledge in organic synthesis planning. The method we decided to explore was to create an axiomatic theory to replace our intuitive theory about chemical synthesis. This formal method of reasoning is very powerful in that it completely eliminates any questions about the method used to reach a conclusion. Since any conclusions reached would be theorems of the axiomatic theory, the acceptability of the conclusions rests completely on the acceptability of the postulates and not upon the method of reasoning. We are then free to focus on the chemical principles which are provided as postulates. 

Expert Systems and Smart Databases as Aids to Organic Synthesis Planning. ... 

Program systems for computer-assisted organic synthesis (CAOS) have been under development since the early 1970s [27]. The program systems for computer-assisted synthesis planning can be subdivided into two groups information-oriented and logic-oriented systems [28]. 

D.P. Curran, Strategy-level separations in organic synthesis from planning to practice, Angew Chem, Int Ed Engl 37 1174-1196 1998. 

Andraos, J. (2005) On Using Tree Analysis to Quantify the Material, Input Energy, and Cost Throughput Efficiencies of Simple and Complex Synthesis Plans and Networks Towards a Blueprint for Quantitative Total Synthesis and Green Chemistry. Organic Process Research and Development, 10, 212-240. 

Bertz, S.H. St Sommer, T.f. (1993) Applications of Graph Theory to Synthesis Planning Complexity, Reflexivity, and Vulnerability. In Organic Synthesis Theory and Applications, Vol. 2 (ed. T. Hudhcky), pp. 67-92. lAI Press, Greenwich, CT. 

Computational techniques in organic chemistry such as for drug design, structure elucidation or synthesis planning quite often investigate enormous numbers of hypothetical molecules, which are not yet... 

D. P. Curran, Strategy-Level Separations in Organic Synthesis From Planning to Practice , Angew. Chem, Int. Ed Engl. 1998, 37,1175. 

In the particular case of natural products, once all the possibilities that the "logic-centred methodology" offers have been explored, it is pertinent to consider the biogenetic pathways by which they are synthesised in Nature since these can be a source of inspiration and may introduce an intrinsic element of elegance into the synthetic plans. In this context, tropine (131 offers a unique example in the history of organic synthesis. In 1902 this rather simple alkaloid was synthesised by Willstatter from cycloheptanone [8] through a sequence of about twenty steps, as shown in Scheme 3.4. 

When planning an organic synthesis in this way, we cannot apply an individual transform only because the corresponding retron is present in the target molecule. It is necessary to carry on an accurate analysis with a perspective (outlook) of several retrosynthetic steps, in order to see if a particularly adequate sequence of transforms exists. 

As an organic chemist I consider reaction mechanisms of crucial importance, both for the classification of reactions and for synthesis-planning. For this reason mechanisms are proposed for almost all the reactions described herein. Most of these mechanisms have not yet been rigorously proven, however, and should be considered as preliminary. 

Dolata, D. P, QED Automated Inference in Planning Organic Synthesis, PhD dissertation, University of California, Santa Cruz 1984. 

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