The concise, scalable, enantioselective synthesis of the STX family (11 natural products prepared or formally accessible), as outlined herein, represents the most straightforward access reported to this classic, medicinally important natural product family. The modular nature of this route can, in principle, enable access to a whole range of natural and unnatural STX analogs. A tactical combination of modern strategies such as radical retrosynthesis (to enable convergency), C-H functionalization (to forge a key C-N skeletal bond), and biocatalysis (to simplify access to trans-3-hydroxyproline) proved essential. The synthetic blueprint disclosed herein should democratize access to these medicinally promising natural products and facilitate the synthesis of even more complex family members.