Basic Principles of DNA-templated Organic Synthesis

In this chapter, we will first discuss the basic principles of DNA-templated organic synthesis, as it is the mechanistic foundations for DNA-encoded libraries then we will discuss the progressive development of DNA-templated libraries and the evolution into a novel drug discovery tool. We will also discuss the DNA-recorded library, which also encodes library molecules with DNA but is conceptually different. These discussions will naturally involve specific drug discovery programs in which these libraries were applied and finally, we will discuss the outlook of DNA-eneoded libraries in the future of drug discovery. 

Our focus in this chapter is the DNA-encoded library as a tool in exploring chemical space for drug discovery. For the applications of DNA-templated synthesis in other fields, such as the origin of life, biodetection, nano-technol-ogy, etc., we refer readers to various excellent reviews.  

Regardless of which one of the above architectures is used, a templated reaction becomes pseudo-intramolecular and the effective molarity created by this effect could exceed 1000 M. In prineiple, if the reagent DNA is placed at a relatively distal position from the template s reactive group, the effective molarity is expected to decrease. However, interestingly, Liu and co-workers have observed that the rates of some DNA-templated reactions, e.g. amide formation, remain nearly constant when the two reactants are separated by even up to 30 bases. They hypothesized, for these so-called distance-independent reactions , the reaction rates are faster than the hybridization  

Initially, the studies of DNA-templated reactions were geared towards the syntheses of analogs of native DNA s phosphodiester linkage, until recently 

3 DNA-templated Multistep Synthesis to Access Complex Chemical Structures 

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