Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• , sulfonamides and aryltrifluoroborates is described. This process provides modular access to the important α-arylglycine motif in moderate to good yields and enantioselectivies. The formed α-arylglycine products constitute useful building blocks for the synthesis of peptides or arylglycine-containing natural

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• data, mass spectrometry sequence tagging, advanced Marfey’s analysis, and the GNPS molecular networking we solved the full structure of digyalipopeptide A (1). We found that compound 1 is a member of a somewhat homologous series of peptides produced as a mixture by the strain containing the same amino

• , 1H, H-7), 4.53 (ov., 1H, H-12), 4.52 (ov., 1H, H-16), 4.18 (ov., 1H, H-22), 4.08 (dd, J = 8.8, 6.0 Hz, 1H, H-33), and 4.44 (ov., 1H, H-27) which were indicative of the presence of α-hydrogens belonging to amino acid residues typical for peptides. Using 1H,1H homonuclear correlation spectroscopy (COSY

• − 99Val) provided the needed sequence information for the structure of compound 1. Stereochemistry determination Historically, the determination of the regiochemistry of enantiomeric amino acid residues within natural product peptides has proved challenging sometimes requiring the strenuous efforts of de

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• conserved across all 40 plus RiPP families [32]. However, each RiPP BGC family features genes encoding characteristic tailoring enzymes, or precursor peptides, that show a high degree of sequence conservation within the family. These conserved genes can be utilized for the targeted, family-specific

• alignments with known genes and domains using algorithms like BLAST (Figure 4) [42]. BLAST detects similar sequences to a given query sequence [42]. The first version of the tool BAGEL utilized BLAST analysis, among others, to identify putative BGCs of bacteriocins (= antimicrobial peptides and proteins) [43

• sequences derived from tailoring enzymes or precursor peptides (Figure 3C and D). These family-specific pHMMs are likewise used in tools like BAGEL or RODEO and enable the identification of novel members of known RiPP families [46][69]. RRE-Finder, which is integrated into the antiSMASH platform and RODEO

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• an aryl or alkynyl unit [16][17][18][19][20][21][22]. In a biological context, the fluoroalkenyl motif could be incorporated into peptides with the expectation that the fluoroalkenyl unit could serve as a peptide isostere and prevent unexpected hydrolysis of these compounds. Recent studies have shown

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• .18.166 Abstract Longicatenamides A–D are cyclic hexapeptides isolated from the combined culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B0596. Because these peptides are not detected in the monoculture broth of the actinomycete, they are key tools for understanding chemical

• developed [4]. Among the isolated longicatenamides, compound 1 exhibits weak but preferential antimicrobial activity against Bacillus subtilis. Because peptides 1–4 are not detected in the monoculture broth of Streptomyces sp. KUSC_F05, they are key tools for understanding chemical communication in the

• chemical communication. The retrosynthesis of peptide 1 is displayed in Scheme 1. First, the cyclic peptide 1 was linearized by retrosynthesis, and acid-labile protecting groups were attached onto the reactive side chain. The biomimetic synthesis of cyclic peptides often enables efficient synthesis [12][13

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• . For example, consider a pair of molecules (Figure 1) that selectively inhibit the Gq11-signaling pathway in cells [15][16]. The molecules are complex cyclic peptides, and the construction of analogs of the molecules to probe the basis of their activity is a significant challenge. In an ideal situation

• chosen as the ligand for Gαi1 because it was known to bind the target with a binding constant of KD = 60 nM [21]. The binding data shown in Figure 5 compared interactions between Gαi1 and two surface bound peptides; R6A (MSQTKRLDDQLYWWEYLC) and a scrambled R6A sequence (QLSEDTYLLMRWDYWQK). The two

• peptides were placed on the array along with a fluorescent dye (LRSC, lissamine rhodamine) that was used to make sure the placement chemistry was working. The array used was coated with the borate ester diblock copolymer (Figure 2), and the peptides were attached to this polymer through a PEG-6 linker in

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• interactions with other proteins. Here, we use a computational approach to predict the binding sites of the designed hybrid compound featuring aggregation-induced emission luminophores as a potential supramolecular ligand for 14-3-3ζ in the presence and absence of C-Raf peptides. Our results suggest that the

• area above and below the central pore of the dimeric 14-3-3ζ protein is the most probable binding site for the ligand. Moreover, we predict that the position of the ligand is sensitive to the presence of phosphorylated C-Raf peptides. With a series of experiments, we confirmed the computational

• that identified putative binding sites of 1 on 14-3-3ζ. These predictions can then be tested in a targeted way. Using this approach, we tried to answer basically two questions: (a) where does compound 1 bind on 14-3-3ζ, and (b) how would the presence of phosphorylated C-Raf peptides in the binding

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• hangtaimycin, TDD and the hangtaimycin degradation product HTM222 are given. Keywords: antibiotics; enantioselective synthesis; peptides; racemisation; Streptomyces; Introduction Hangtaimycin (1, Scheme 1) was first isolated from Streptomyces spectabilis and shown to possess weak antimicrobial activity

• DBU is a common strategy for the dehydration of serine and threonine units in peptides [16], but unfortunately the acetylation of 10 failed. Interestingly, the direct treatment of 10 with LiClO4 and DBU under prolonged reaction times (3 days) resulted in the elimination of water. This reaction

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• -substituted glycines [1][2]. They retain the same backbone as peptides except that the side chains are located on the nitrogen atoms of the amide bonds and thus represent an important class of peptide biomimetics [3][4][5], generally with improved cell permeability [6] and proteolytic resistance [7][8

• ]. Beyond their resemblance to peptides, the obvious interest in this family of peptidomimetics arises from their ease of synthesis by the modular submonomer protocol [9] which enables the incorporation of numerous primary amine synthons in a sequence-controlled manner [10], and application of solid

• -supported combinatorial approaches [11][12][13]. The most relevant comparison of peptoids with peptides is in fact with polyprolines due to the presence of backbone tertiary amide linkages, much more prone to cis/trans equilibria than secondary amides. Indeed, in proteins, cis-amide bonds are most often

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• early to stimulate greater developments. Things started to change in the late 1990s when short-chain peptides [3], carbohydrate-based ketones [4][5], and thioureas [6] were shown to catalyze enantioselective transformations. The real breakthrough came in the year 2000 when two teams independently

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• metabolites for self-defense in different microorganisms, peptidic natural products are assembled either by ribosomal synthesis or by non-ribosomal peptide synthetases (NRPS) [2]. Macrocyclic peptides are pervasive throughout this class of natural products and often show improved stability against proteolytic

• and Discussion Since a couple of years the focus of our research group is on the synthesis of unnatural amino acids and their incorporation into complex natural products. Many of these show interesting anticancer activities [26][27][28]. Some linear peptides, such as pretubulysin bind to tubulin [29

• the peptide can have a significant effect on the Claisen rearrangement and therefore we synthesized the Cbz- as well as the Boc-protected peptides 8a and 8b. The tripeptide building blocks were previously also used in the Cyl-1 synthesis. Glycine allyl ester 5 was Boc-deprotected to give amine 7 as

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• cells by a naphthyl-capped phosphopeptide (Nap-ffpy, 1), we conjugated the heteroaromatic dipyrrole or tripyrrole motif at the N-terminal of short peptides containing phosphotyrosine or phosphoserine and examined the bioactivity of the resulting phosphopeptides (2–10). Although most of the

• of 1. These results suggest that a heteroaromatic motif at the N-terminal of peptides likely disfavors the formation of extensive nanofibers or morphological changes during enzymatic self-assembly, thus provide useful insights for the development of phosphopeptides as substrates of phosphatases for

• controlling cell fate. Keywords: cells; enzyme; N-terminal; peptides; pyrroles; self-assembly; Introduction Biomacromolecular assemblies have received considerable attention recently in the field of biomaterials [1][2][3][4][5][6][7], among which peptides are of particular interest because of their unique

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• from 2.5 to 7.9 Mbp, biosynthetic gene clusters for siderophores, terpenes, and non-ribosomal peptides were identified by genome mining [39], suggesting a high capability of secondary metabolism in this genus. Further investigation is underway to disclose the actual diversity of metabolites from the

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• widely used as building blocks to prepare various heterocyclic peptides [17][18][19][20][21][22]. In particular, 1,2-oxazole amino acid derivatives, such as compounds V [20], VI [21], and VII, VIII [22], can be easily synthesized and are suitable for insertion with the corresponding heterocycle into a

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• biological activities, especially applications in the field of medicinal chemistry. β-Amino acids (i.e., amino acids containing an extra methylene group in the backbone) occur naturally in peptidic structures [1][2][3][4][5] and have been used in peptide design to obtain mixed peptides that retain their

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

• –Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to

• 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

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• peptides, proteins and nucleic acids and to evade undesired immune responses, monodisperse PEGs are required or highly desired [12][13]. To meet the needs of monodisperse PEGs, significant efforts have been made to develop stepwise methods for their synthesis [14][15][16][17][18][19][20][21][22][23][24][25

• frequently adopted. For example, in peptide synthesis, peptides with acid-labile side chain protections can be selectively cleaved from the acid-labile 2-chlorotrityl resin with dilute TFA [34]. In RNA synthesis, the acid-sensitive 2'-TOM protecting groups can survive the acidic conditions for removing the 5

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• Haopei Wang Zachary T. Ball Department of Chemistry, Rice University, Houston TX, USA 10.3762/bjoc.17.202 Abstract Photo-responsive modifications and photo-uncaging concepts are useful for spatiotemporal control of peptides structure and function. While side chain photo-responsive modifications

• ” amide products can and does occur under physiological conditions, the rates of this hydrolysis are slow for the simple models in this study. Within more complex peptides or proteins, selectivity in photocleavage pathways may differ significantly, depending on local chemical environment. It is also worth

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• cytotoxicity compared to hoshinoamide B. Herein, we report the initial progress on the total synthesis of hoshinomaide A. The key challenges for the total synthesis of hoshinoamide A are the coupling of highly methylated amino acids and the purification of hydrophobic peptides. Results and Discussion As shown

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• development [1][2][3][4][5][6][7][8]. This objective has been proposed to be achieved by the synthesis of chemically homogeneous glycoconjugates bearing the O-antigen oligosaccharide conjugated to peptides for eliciting the desired immune response through vaccines [9][10][11][12][13][14][15][16][17][18][19

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• posttranslational modifications of peptides in proteomics can be adapted to specifically identify glycopeptides. What is also obvious for glycobioinformatics is that it needs an own language that is understood by both computers and researchers to facilitate the exchange of glyco-specific information as well as the

• article by Barnett et al. [2] uses molecular dynamics to show that O-linked glycosylation alters peptide conformation, which influences the binding of the peptides to antibodies, despite the fact that glycans are not directly involved in the binding. Another molecular modeling article by Fogarty et al. [3

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• cryogels include fertilizers for agrochemical applications [103], peptides [104], proteins [37], and growth factors [81][105][106]. For example, Lee et al. reported the use of a double cryogel structure for the delivery of growth factor for enhanced bone regeneration [105]. 5.4. Cryogels in wound healing

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• peptides and proteins have been linked to nanotechnology. DQA and TPP are both cationic and lipophilic molecules and therefore able to easily pass the mitochondrial membrane [15][16][17][18][19]. TPP is the most-studied mitochondrial targeting agent and has shown to accumulate 1000 times more in the

• non-specific protein absorption. Su et al. [40] investigated the effects of a protein corona on active and passive targeting using 20 different types of PEGylated gold nanoparticles, which were decorated with cyclic RGD (arginylglycylaspartic acid) peptides. As a result, the active targeting

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• of natural products (especially macrocycles) [12], alkaloids [13], amino acids and functionalized biomolecules such as peptides [14][15][16][17][18][19][20] or various drugs [21]. Due to the ring strain, bicyclic systems and derivatives, such as norbornadiene derivatives can easily be converted

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• called “heparin crisis” in 2008 [4]. In addition, the heterogeneity of naturally sourced samples poses a severe bottleneck to the molecular characterization of polysaccharides that dwarfs in comparison to other biomolecules like peptides and nucleic acids. Establishing structure–property correlations is