Suzuki–Miyaura Reaction in the Presence of N-Acetylcysteamine Thioesters Enables Rapid Synthesis of Biomimetic Polyketide Thioester Surrogates for Biosynthetic Studies

Biomimetic N-acetylcysteamine thioesters are essential for the study of polyketide synthases, non-ribosomal peptide synthetases and fatty acid synthases. The chemistry their preparation is, however, limited by specific functionalization susceptibility to undesired side reactions. Here we report a method rapid (SNAC) 7-hydroxy-2-enethioates, which suitable various enzymatic domains megasynthase enzymes. is based on one-pot sequence hydroboration Suzuki–Miyaura reaction. optimization reaction conditions made it possible suppress potential reactions introduce highly functionalized SNAC methacrylate unit in high yield. versatility was demonstrated synthesis complex polyketide-SNAC 12 33. Brown crotylation followed enabled introduction target motif significantly fewer steps with higher overall yield stereoselectivity than previously described approaches. This first transition-metal-catalyzed cross-coupling presence an thioester.