Solid-phase synthesis of a putative heptapeptide intermediate in vancomycin biosynthesis

Chapter 19 In Vitro Studies of Phenol Coupling Enzymes Involved in Vancomycin Biosynthesis

“…The assembly of 1-OH can be achieved efficiently using N-allyloxycarbonyl (Alloc) protected amino acids by solid-phase synthesis on chlorotrityl chloride (CT) resin (Freund and Robinson, 1999;Li and Robinson, 2005). Where necessary, N-Alloc and side chain O-allyl protecting groups can be removed using Pd-catalysis under neutral conditions.…”

ChemInform Abstract: Orthogonal Protecting Groups for N‐α‐Amino and C‐Terminal Carboxyl Functions in Solid‐Phase Peptide Synthesis

“…PhSiH 3 also has been used as a scavenger in the SPS of a putative heptapeptide intermediate in the vancomycin biosynthesis 78 and also for Leu-enkephalin. 79 In this case, minor impurities Ͻ2% due to the corresponding allylpeptides were detected.…”

Solid-Phase Synthesis Using (Allyloxy)carbonyl(Alloc) Chemistry of a Putative Heptapeptide Intermediate in Vancomycin Biosynthesis Containing m-Chloro-3-hydroxytyrosine

“…To address these questions, access is required to putative heptapeptide substrates such as 1. In earlier work [7], we reported a convenient solidphase synthesis of the related heptapeptide 3. We now show that the solid-phase methods developed earlier may also be used to allow convenient access to heptapeptides such as 1 and 2.…”

“…The widely used solid-phase Fmoc-or Boc-chemistries, which require basic or acidic conditions at each step of chain elongation, appeared to be unsuitable for the synthesis. For this reason, we favoured the use of Alloc 1 ) chemistry [8], and could show in earlier work that 3 can be prepared in good yield by this methodology [7]. To apply the same approach here, we first set out to synthesize the suitably protected building blocks 4 ± 10 (11 is available commercially).…”

“…Peptide Synthesis. The solid-phase synthesis of peptide 1 was performed as described in [7] on 2-chlorotrityl-chloride resin. The first amino acid, 4, was coupled to the resin in CH 2 Cl 2 with NMM as base, without significant epimerisation.…”