Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• stapling techniques to stabilise α-helical secondary structure motifs of peptides led to the design of modulators of protein–protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki

• its native binding partner β-catenin. An increased proteolytic stability against proteinase K has been demonstrated. Keywords: accelerated molecular dynamics; halotryptophan; intrinsically disordered peptides; late-stage diversification; macrocyclisation; molecular dynamics; stapled peptides; Suzuki

• , metabolic diseases and neurological disorders [8], which had been considered undruggable for a long time due to their large contact area and shallow surface [9]. Since then, many other reactions have been investigated for macrocyclisation with the objective of peptide stapling [10] including lactam- [11][12

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• product 30 carrying an 8-OPMP group was obtained from PMP-protected polyketide 28. The endgame of a total synthesis of seragamide A (2) will have to address the macrocyclisation, desilylation of the threonine moiety, and O-demethylation of the D-iodotyrosine unit of 31. In orienting reactions on small

• scale, desilylation of 31 (TBAF) was a spot-to-spot conversion. Saponification of both the silylated and desilylated methyl esters with LiOH was possible, as long as very mild acidic conditions were applied on work-up. However, macrocyclisation of the TIPS-protected or the desilylated acid did not occur

• to liberate the free carboxylic acid 29 and to couple it with the protected tripeptide 27 that was obtained by solution phase synthesis. We will now aim at the macrocyclisation of analogues of compound 31, which will probably require replacement of the bulky TIPS group installed at the threonine unit

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• to show that one of its domains (PatGmac) possesses similarity to subtilisin-like peptidases [104][107]; accordingly, this catalyses macrocyclisation via a serine protease-like mechanism. PatG features a canonical serine protease-like catalytic triad (Asp548, His618 and Ser783), which cuts before an

• macrocyclisation found in NRP biosynthesis, although the energetic demands of breaking an amide bond versus a thioester bond are notably different. PatG may have synthetic utility, as studies with unnatural substrates have shown that macrocycles of between 5–22 residues can be produced [108], despite it naturally

• AgrD contains an N-terminal signal peptide that is cleaved by an endogenous peptidase [120]. Unlike other macrocyclisation peptidases, AgrB does not belong to a well-characterised peptidase family, but mutagenesis experiments on Cys86 infer that a cysteine protease-like mechanism acts to generate a

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• aldehyde fragment 6 by asymmetric alkynylation, and form the pyran using an oxa-Michael addition, in a manner reminiscent of that employed by Uenishi and co-workers [34]. Finally, macrocyclisation will be achieved through the well-established strategy of ring-closing metathesis at C8–C9. Results and