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Intramolecular Suzuki–Miyaura Reaction for the Total Synthesis of Signal Peptidase Inhibitors, Arylomycins A 2 and B 2
Author(s) -
Dufour Jeremy,
Neuville Luc,
Zhu Jieping
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201000924
Subject(s) - intramolecular force , yield (engineering) , chemistry , stereochemistry , total synthesis , nitro , combinatorial chemistry , sequence (biology) , organic chemistry , materials science , biochemistry , alkyl , metallurgy
Development of the total syntheses of arylomycins A 1 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 A 2 was obtained in 13 steps from L ‐Tyr for the longest linear sequence, in 13 % overall yield. Arylomycin B 2 was synthesized in 10 steps from L ‐3‐nitro‐Tyr, in 10 % overall yield.