Intramolecular Suzuki-Miyaura reaction for the total synthesis of signal peptidase inhibitors, arylomycins A2 and B2

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)]


Published in:
Chemistry--A European Journal, 16, 34, 10523-10534, S10523/1-S10523/76
Year:
2010
Keywords:
Note:
34-3, Amino Acids, Peptides, and Proteins, Institut de Chimie des Substances Naturelles, Centre de Recherche de Gif,CNRS,Gif-sur-Yvette,Fr., Journal, 0947-6539, written in English., 65979-36-4 (Signal peptidase) Role: BSU (Biological study, unclassified), BIOL (Biological study) (total synthesis of signal peptidase inhibitors arylomycins A2 and B2 via Suzuki-Miyaura coupling, incorporation of methylhydroxyphenylglycine into cyclization precursor and segment coupling); 107-82-4 (1 bromo 3 methylbutane); 4548-78-1 (Isopentylmagnesium bromide); 5575-03-1; 10065-72-2; 15761-38-3; 23680-31-1; 29823-18-5; 67706-14-3; 71400-63-0; 73183-34-3; 201733-56-4 Role: RCT (Reactant), RACT (Reactant or reagent) (total synthesis of signal peptidase inhibitors arylomycins A2 and B2 via Suzuki-Miyaura coupling, incorporation of methylhydroxyphenylglycine into cyclization precursor and segment coupling); 2724-56-3P; 113850-71-8P; 193085-38-0P; 872414-47-6P; 1086702-96-6P; 1086702-98-8P; 1086703-01-6P; 1086703-03-8P; 1086703-05-0P; 1086703-08-3P; 1086703-10-7P; 1086703-14-1P; 1086703-19-6P; 1086703-22-1P; 1086703-24-3P; 1253795-07-1P; 1253795-08-2P; 1253795-09-3P; 1253795-10-6P; 1253795-11-7P; 1253795-12-8P; 1253795-13-9P; 1253795-15-1P; 1253795-16-2P; 1253795-18-4P; 1253795-19-5P; 1253795-20-8P; 1253795-21-9P; 1253795-22-0P; 1253795-23-1P; 1253795-24-2P; 1253795-25-3P; 1253795-26-4P; 1253795-27-5P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (total synthesis of signal peptidase inhibitors arylomycins A2 and B2 via Suzuki-Miyaura coupling, incorporation of methylhydroxyphenylglycine into cyclization precursor and segment coupling); 71026-62-5P; 1086703-12-9P; 1253795-14-0P; 1253795-17-3P Role: SPN (Synthetic preparation), PREP (Preparation) (total synthesis of signal peptidase inhibitors arylomycins A2 and B2 via Suzuki-Miyaura coupling, incorporation of methylhydroxyphenylglycine into cyclization precursor and segment coupling)
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 Record created 2010-11-25, last modified 2018-12-03


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