Strategic disconnection

The most useful general criteria for the assessment of acyclic strategic disconnections are summarized below. Most of these are based on the retrosynthetic preservation of building blocks and expeditious reduction of molecular size and complexity. 

Cocyclic vicinal exendo bonds, especially in centrally-located rings may be selected for topologically strategic disconnection. Structures 124 and 125 are provided for illustration. One reason for the effectiveness of such disconnections is that it can signal the application of various annulation transforms. The broken bonds may involve heteroatoms such as N, O and S. 

The co-occurring marine allomones 2- and 9-isocyanopupukeanane have been synthesized from a common intermediate. This condition along with topologically based strategic disconnection had a major impact on the retrosynthetic analysis. 

Venustatriol, a marine-derived antiviral agent, as with many polyether structures, is a straightforward problem for retrosynthetic analysis. The major issues, clearance of stereocenters and topologically strategic disconnection, were readily resolved to generate the pathway of synthesis described below. 

It is clear from the examples in this book that the use of biocatalysis can produce some very cost-effective and environmentally acceptable processes, and the authors anticipate that the use of this technology will increase as synthetic organic chemists realize its value and begin to look for strategic disconnections in the synthetic sequence of new target molecules where a biocatalytic step can be applied to utmost benefit. Thus, biocatalysis should be seen as a routine part of the synthetic toolbox and, in some cases, the reagent of choice for transformations such as the reduction of ketones to chiral alcohols, and not as a technology of last resort when all else has failed. 

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