Rapid Syntheses of (-)-FR901483 and (+)-TAN1251C Enabled by Complexity-Generating Photocatalytic Olefin Hydroaminoalkylation

Abstract

We report a common strategy to facilitate the syntheses of the polycyclic alkaloids (-)-FR901483 (1) and (+)-TAN1251C (2). A divergent synthetic strategy provides access to both natural products through a pivotal spirolactam intermediate (3), which can be accessed on a gram-scale. A photocatalytic olefin hydroaminoalkylation brings together three readily available building blocks and forges the majority of the carbon framework present in 1 and 2 in a single operation, leading to concise total syntheses. The complexity-generating photocatalytic process also provides direct access to novel non-racemic spirolactam scaffolds that are likely to be of interest to early-stage drug discovery programs.

Keywords: amine synthesis; medicinal chemistry; photoredox chemistry; radical chemistry; total synthesis.