The Looper approach to STX is the most efficient strategy reported thus far and features a sequential oxidative alkyne functionalization . These path-pointing studies, however, were all linear in nature and thus proceeded with low efficiency and modularity for rapid analog preparation. Herein we disclose a fundamentally different approach to the STX challenge that maximizes skeletal bond forming events and convergency through the application of radical retrosynthetic disconnections, C-H functionalization logic, and biocatalysis resulting in the most efficient synthesis of STX and related family members to date.