E- and Z-trisubstituted macrocyclic alkenes for natural product synthesis and skeletal editing.

ABSTRACT: Many therapeutic agents are macrocyclic trisubstituted alkenes but preparation of these structures is typically inefficient and non-selective. A possible solution would entail catalytic macrocyclic ring-closing metathesis, but these transformations require high catalyst loading, conformationally rigid precursors and are often low yielding and/or non-stereoselective. Here we introduce a ring-closing metathesis strategy for synthesis of trisubstituted macrocyclic olefins in either stereoisomeric form, regardless of the level of entropic assistance. The goal was achieved by addressing several unexpected difficulties, including complications arising from pre-ring-closing metathesis alkene isomerization. The power of the method is highlighted by two examples. The first is the near-complete reve

SUBMITTER: Mu Y 

PROVIDER: S-EPMC9191848 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature