Intramolecular Suzuki-Miyaura reaction for the total synthesis of signal peptidase inhibitors, arylomycins A2 and B2
2010
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)]
Details
Title
Intramolecular Suzuki-Miyaura reaction for the total synthesis of signal peptidase inhibitors, arylomycins A2 and B2
Author(s)
Dufour, Jeremy ; Neuville, Luc ; Zhu, Jieping
Published in
Chemistry--A European Journal
Volume
16
Issue
34
Pages
10523-10534
Date
2010
Keywords
Antibiotics; Enzyme inhibitors; Macrocyclization; Natural products; Peptide coupling; Rotamers; Suzuki coupling reaction (total synthesis of signal peptidase inhibitors arylomycins A2 and B2 via Suzuki-Miyaura coupling; incorporation of methylhydroxyphenylglycine into cyclization precursor and segment coupling); Cyclic peptides; Heterocyclic compounds; Macrocyclic compounds 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); cyclic peptide arylomycin total synthesis signal peptidase inhibitor rotamer; Suzuki Miyaura coupling methylhydroxyphenylglycine cyclization peptide coupling
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)
Laboratories
LSPN
Record Appears in
Scientific production and competences > SB - School of Basic Sciences > ISIC - Institute of Chemical Sciences and Engineering > LSPN - Laboratory of synthesis and natural products
Peer-reviewed publications
Work outside EPFL
Journal Articles
Published
Peer-reviewed publications
Work outside EPFL
Journal Articles
Published
Record creation date
2010-11-25