Divergent synthesis of complex diterpenes through a hybrid oxidative approach
Xiao Zhang, Emma King‐Smith, Liao‐Bin Dong, Li‐Cheng Yang, Jeffrey D. Rudolf, Ben Shen, Hans Renata
Abstract
Trio of enzymes power divergent synthesis Diterpene natural products are built from a 20-carbon building block, with a huge range of possible structures and modifications. Chemical synthesis of specific molecules, some of which have valuable biological activities, is tricky because of the need for selective oxidations and rearrangements when starting from widely available scaffolds. Zhang et al. characterized selectivities for three oxidative enzymes that each attack different positions on a common scaffold. They then seamlessly combined chemical transformations with the enzymatic oxidations to produce nine distinct compounds across three families of diterpenes. These results highlight the potential of hybrid organic-biocatalytic synthetic schemes for divergent synthesis. Science , this issue p. 799