Science of Synthesis

Wever, R.; Babich, L.; Hartog, A. F., Science of Synthesis: Biocatalysis in Organic Synthesis, (2015) 1, 224.

Chemical phosphorylation procedures are still used and in general they involve very reactive compounds (e.g., POCl3, phosphorochloridates, or N-phosphoryloxazolidinones), resulting in undesired side reactions. Moreover, large biomolecules containing many potential phosphorylating sites require various protection and deprotection steps in order to achieve the desired regiospecific phosphorylation, which results in poor overall yields[‌22‌] and considerable waste. Furthermore, the high polarity of phosphate makes conventional purification difficult. Several procedures for the protection/deprotection of phosphorylated sites have been developed. Some protecting groups are removed via a less specific P—O bond fission, whereas others are removed via a C—O cleavage that reduces side reactions and is therefore more widely used.[‌23‌] In contrast, the more environmentally friendly enzymatic phosphorylations eliminate many of these steps and are often diastereo-, enantio-, and regioselective. The prime role of phosphorylated compounds in metabolism makes them an important target for the synthetic chemist. In this chapter the synthesis of a variety of phosphorylated compounds using a range of phosphorylating enzymes is described. In addition, the use of phosphorylated compounds as activated intermediates in enzymatic cascade reactions will be discussed. For details regarding the catalytic mechanisms of some of the enzymes involved, the reader is referred to a recent review,[‌24‌] and references cited therein.

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