Ranking of Synthesis Plans

Abstract Hendrickson s definition of the ideal synthesis serves as a benchmark to assess synthesis plans. Criteria such as convergency, increase in complexity, and robustness are presented to rank synthesis plans and to pinpoint weaknesses therein. 

Any ranking of plans for the synthesis of a given target compound depends on benchmarks which must he defined. Possible criteria may be 

An ideal synthesis has been postulated by Turner [3] and by Wender [4,5] as a one-pot reaction in which all starting materials are mixed, leading directly to the final product. 

Given the present imperfection of one-pot syntheses [6], this definition of the ideal synthesis is utopian, at least for in vitro chemical synthesis. One has to admit, though, that the in vivo biosynthesis of natural products in a living cell by and large fulfills the criterion of a so-defined ideal synthesis. 

I would prefer a more realistic definition of the ideal synthesis, one from which guidelines for the planning of syntheses can be derived. This is the definition by Hendrickson [7]  

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The required masses and raw material costs of any starting material or intermediate in a plan, including the final target product, may be determined by inspection. Overall kernel RME is shown to trump overall yield as the key metric to rank material efficiency of a synthesis plan. 

Table 4.7 Summary of reaction metrics and synthesis according to overall kernel (maximum) RME. tree parameters for nicotine synthesis plans ranked ...

A complete ranking of these synthesis plans according to waste production so that you can pick ont those plans that have a green advantage and others that would be targets for improvement... 

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