Bidirectional approaches

The direct goal of stereochemical strategies is the reduction of stereochemical complexity by the retrosynthetic elimination of the stereocenters in a target molecule. The greater the number and density of stereocenters in a TGT, the more influential such strategies will be. The selective removal of stereocenters depends on the availability of stereosimplifying transforms, the establishment of the required retrons (complete with defined stereocenter relationships), and the presence of a favorable spatial environment in the precursor generated by application of such a transform. The last factor, which is of crucial importance to stereoselectivity, mandates a bidirectional approach to stereosimplification which takes into account not only the TGT but also the retrosynthetic precursor, or reaction substrate. Thus both retrosynthetic and synthetic analyses are considered in the discussion which follows. 

This section deals with the question of whether there are quantitatively detectable and interpretable correlations between the dose of an administered drug, or the concentration of a drug and its metabolites measured in the blood or plasma (blood or plasma level), and the therapeutic action or side effects observed. Investigations relating to questions of this type are called PK PD (pharmacokinetic pharmacodynamic) studies. The PK PD analysis is a bidirectional approach pharmacokinetics represent what the body does with a drug, and pharmacodynamics describes what a drug does to the body. The PK PD analyses are key elements of early drug development, and PK PD trials are able to answer specific disease-related efficacy and safety questions. 

Synthetic strategies differ by binding either the glycosyl donor [105] or the glycosyl acceptor to the solid phase. A bidirectional approach [106], which allows for chain elongation in both directions, has also been reported. 

These actors play the primary parts in the supply chain of substances and products. All of them are involved in the communication process because a correct communication process requires a bidirectional approach involving all actors (upstream and downstream). 

A symmetric oligomer chain elongation approach was introduced by Tour et al. [168-170]. This group developed a bidirectional approach to the solid phase synthesis of oligo phenylene ethynylenes (Scheme 7.8). 

Qu employed a bidirectional approach to the synthesis of glabrescol (139 Scheme 4.42) [77]. Pentaepoxide 187, formed through a Shi oxidation, was subjected to NaOH to deliver the natural product directly. 

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