Strategic synthesis planning

Apart from its use for solvation and separation of catalysts, the fluorous phase can also be used advantageously for separation processes during workup. Strategic synthesis planning is facilitated by tagging with fluorous residues to overcome the frequently limiting recovery and purification difficulties [1], As in solid-phase syntheses, an excess of components can be used to drive the reactions to completion. Side products can easily be separated if, for example, only the product is tagged with fluorous alkyl residues and therefore precipitates from the reaction mixture or is extracted with the fluorous phase. 

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. 

The Knowledge base-Oriented System for Synthesis Planning (KOSP) was developed by Satoh and Funatsu and uses reaction databases for the retrosynthe-sis approach [115]. KOSP provides strategic site-pattern perception and precursor skeleton generation and evaluates retrosynthetic schemes. This system is based on knowledge bases in which reactions are abstracted by structural or stereo characteristics of reaction sites and their environments. 

The multi-valued predicate calculus logic as implemented in QED has been demonstrated to be suitable for cleanly representing strategic axioms of chemical synthesis. QED is a powerful tool for exploring inference in the planning of synthesis strategies. QED helped us elucidate key strategic concepts and their interdependence and... 

From a tactical perspective, early retrosynthetic removal of the epoxy dienediyne core must dominate all synthetic planning for (+ )-neocarzi-nostatin, since its presence in any intermediate will render that molecule highly susceptible to nucleophilic attack, and will jeopardise the success of all the remaining chemistry. In essence, it would be strategically advisable to install the epoxy dienediyne unit late in a forward total synthesis of ( + )-neocarzinostatin. 

---