Directed Metalation–Suzuki–Miyaura Cross-Coupling Strategies: Regioselective Synthesis of Hydroxylated 1‑Methyl-phenanthrenes

A general, efficient, and regioselective synthesis of a series of hydroxylated 1-methylphenanthrenes <b>9</b> by a combined directed ortho metalation (DoM)–Suzuki–Miyaura cross-coupling–directed remote metalation (DreM) sequence is reported. Diversity to this methodology was achieved by a regioselective DoM rather than DreM reaction, affording more highly substituted phenanthrols (Table ). Application of the turbo-Grignard reagent (<i>i</i>-PrMgCl·LiCl) in the Ni-catalyzed Corriu–Kumada reaction gave efficient decarbamoylation (Tables and ). Additional features are the TMS protecting group and halo-induced ipso-desilylation tactics applied to the regioselective synthesis of phenanthrenes (Scheme )

Chemoselective Dual Labeling of Native and Recombinant Proteins

The attachment of two different functionalities in a site-selective fashion represents a great challenge in protein chemistry. We report site specific dual functionalizations of peptides and proteins capitalizing on reactivity differences of cysteines in their free (thiol) and protected, oxidized (disulfide) forms. The dual functionalization of interleukin 2 and EYFP proceeded with no loss of bioactivity in a stepwise fashion applying maleimide and disulfide rebridging allyl-sulfone groups. In order to ensure broader applicability of the functionalization strategy, a novel, short peptide sequence that introduces a disulfide bridge was designed and site-selective dual labeling in the presence of biogenic groups was successfully demonstrated