Abstract

Development of the total syntheses of arylomycins A1 and B2 is detailed. Key features of our approach include (1) formation of 14-membered meta,meta-cyclophane by an intramol. 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. [on SciFinder (R)]

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