DNA-templated synthesis

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

Since the first demonstration that DNA can act as a scaffold for metallization to produce conducting wires [270], the proposal to create circuits on a nanometre size scale has appeared achievable. With CMOS technology predicted to reach a miniaturization limit by 2012 [271], and the high cost and low throughput associated with nanometre scale scanning probe and electron beam lithographic top-down techniques, the DNA-templated synthesis of wires with widths typically less than 50 nm may provide a scheme to cir-... 

Kanan MW, Rozenman MM, Sakurai K, Snyder TM, Liu DR. Reaction discovery enabled by DNA-templated synthesis and in... 

DNA-Templated Organic Synthesis. An exciting recent concept developed largely by Liu and co-workers is DNA-templated organic synthesis. DNA-templated synthesis generates products individually linked to ODNs that encode and direct their synthesis. DNA-templated synthesis is limited by the fact that DNA-linked reagents need to be prepared, reactions need to be... 

In DNA-directed and DNA-templated synthesis, the role of DNA is to direct the catalytic metal ion towards the substrate. This implies automatically that the substrates are polynucleotides. Applications of this concept are typically found in DNA modification reactions (e.g., DNA cleavage) and sensing. 

Summerer. D. Marx. A. DNA-templated synthesis More versatile than expected. Angew. Chem.. Int. Ed. Engl. 2002, 41. 89-90. 

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. ... 

Figure 8.4 Other architectures for DNA-templated synthesis, (a) Use of Q architecture to bring the reactive groups together for distal reac-...

Structurally complex molecules are prepared by multistep reactions. The Q architecture and distance-independent reactions have enabled a single DNA template to direct multiple reactions at different regions. However, after eaeh reaction, strategies need to be developed to remove the reagent DNA strand and to purify the template-linked product from unreacted template in preparation for the next step. A variety of cleavable linker strategies and solid-phase-based affinity purification have been developed to address these two key aspects of multistep DNA-template synthesis. 

Figure 8.6 Solid-phase-based purification strategy for DNA-templated synthesis. Reprinted with permission from Professor David R. Liu.

Besides the control of effective molarity, another fundamental principle of DNA-template synthesis is its sequence specificity, which controls the... 

Figure 8.9 Scheme for DNA-templated synthesis of a 13 824-membered macrocwclic fumaramide library.Reprinted, with permission, from Tse et 2008 American Chemical Society. 

Gartner, Z.J., Kanan, M.W., and Liu, D.R. (2002) Expanding the reaction scope of DNA-templated synthesis. Angewandte Chemie International Edition, 41, 1796-1800. 

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