Innovation in protecting-group-free natural product synthesis

Many natural products have intriguing medicinal properties that arise from their fascinating chemical structures. This structural complexity means that the total synthesis of natural products often requires the use of protecting-group chemistry, an approach that is neither economical nor biomimetic. However, structurally complicated and bioactive natural products can be accessible through protecting-group-free (PGF) total syntheses, which are usually much more efficient, provided that the individual reactions proceed with high chemoselectivity. In this Review, we present innovations in methodology and strategy that have enabled the PGF construction of sophisticated organic skeletons bearing multiple asymmetric centres and functional groups. We begin by describing the history of PGF synthesis and then focus on illustrative examples of PGF total syntheses of terpenes and alkaloids reported from 2013 to 2017. These advances will enable more concise and efficient syntheses of molecules of structural and biological importance