Intramolecular suzuki-miyaura reaction for the total synthesis of signal peptidase inhibitors, arylomycins A2and B2

Article abstract of DOI:10.1002/chem.201000924

Development of the total syntheses of arylomycins A₁ and B ₂ is detailed. Key features of our approach include 1) formation of 14-membered meta, meta-cyclophane by an intramolecular Suzuki-Miyaura reaction; 2) incorporation of N-Me-4-hydroxyphenylglycine into the cyclization precursor, which avoids the late-stage low-yielding N-methylation step; 3) segment coupling of a fully elaborated peptide side chain to the macrocycle, which makes the synthesis highly convergent. Overall, arylomycin A₂ was obtained in 13 steps from L-Tyr for the longest linear sequence, in 13% overall yield. Arylomycin B₂ was synthesized in 10 steps from L-3-nitro-Tyr, in 10% overall yield.