Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• thioesterase (TE) domain and determines the topology of the final NRP product. The TE may release the NRP as a linear peptide or cyclic peptide, and the latter further manifests many possible topologies (Figure 5b). In a nutshell, offloading is a TE-catalyzed nucleophilic attack to release an NRP from the

• megaenzyme machinery. Water can act as the nucleophile during the offloading step, which amounts to hydrolysis and results in a linear peptide. On the other hand, a cyclic peptide forms when an intramolecular functional group acts as the nucleophile in this step. Regardless of the resulting topology, the NRP

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• ; transcriptome mining; Introduction Plants are prolific producers of cyclic peptide natural products, making 1000s of different molecules [1]. While the orbitide [2] and cyclotide [3] classes of peptides are well known, it has been recently discovered that a new class of molecules called burpitides are also

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• . heteromorphus CBS 117.55 on rice solid medium yielded an organic-soluble extract, which was subjected to fractionation using preparative HPLC-PDA-ELSD and purification by semipreparative HPLC-PDA; this led to the isolation of a new cyclic peptide 1, along with unguisin B (2, Figure 2). The structure of the new

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

• acid sequence in the cyclic peptide backbone but differing only by the length of aliphatic fatty acid side chains. When tested against Trypanosoma brucei subsp. brucei strain GUTat 3.1 and Leishmania donovani (Laveran and Mesnil) Ross (D10), digyalipopeptide A (1) gave IC50 values of 12.89 µM (suramin

• , analysis of the LC–HRESIMSn showed the presence of several b and y sequence tag ions indicating fragmentations from the middle of the cyclic peptide and most importantly the specific positions of each amino acid residue (Figure 4). Due to the presence of the free hydroxy groups of aspartic and glutamic

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

• 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

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

• studies were initiated with a macrocyclisation between a 7-bromotryptophan and a 4-pinacolatoborono phenylalanine side chain to generate the cyclic peptide P1b (Scheme 2A and B). The intramolecular SMC took place with full consumption of the starting material and without formation of an intermolecular

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• cyclic peptide motif (Scheme 11). Dipeptide substrate 26f decorated with a Morita–Baylis–Hillman carbonate underwent the intramolecular C–H allylation process to yield cyclic peptide 28f under dilute reaction conditions. This macrocyclization strategy introduces an exocyclic olefin motif onto the cyclic

• peptides. B) Intramolecular late-stage alkynylative cyclic peptide formation. a0.05 mol % of BPh3 was added. Late-stage Mn-catalyzed C–H allylation of peptides and bioactive motifs. Intramolecular C–H allylative cyclic peptide formation. Late-stage C–H glycosylation of tryptophan analogues. Late-stage C–H

• peptide, which can be further utilized as a Michael acceptor for a variety of nucleophiles. Based on their manganese-catalyzed allylation using Morita–Baylis–Hillman carbonates, the Ackermann group established an applicable late-stage C–H glycosylation of peptides (Scheme 12) [95]. Thus, allylative

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• peptides that can be used as gene transfection vectors [36]. Unlike linear Schmuck peptides, the cyclic peptide 16 can self-assemble into nanofibers due to the binding between the GCP moiety and the backbone of an adjacent peptide. This binding interaction could stabilize the stacking of peptides by

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• culture extract of the strain Pseudosporangium sp. RD062863. Consequently, HPLC–DAD analysis-guided purification led to the discovery of a novel cyclic peptide, pseudosporamide (1), and three new 26-membered macrolides, pseudosporamicins A–C (2–4, Figure 1). Results and Discussion The producing strain was

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• emerged as a promising approach for treatment. (R)-2,5-Difluorophenylalanine is a required building block for the synthesis of LY2497282 [50][124] (Figure 9). 5.2.5. Ulimorelin: Ulimorelin (187) is a small cyclic peptide containing ᴅ-4-FPhe. Ulimorelin acts as a selective agonist of the ghrelin/growth

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• natural products have been isolated from sponge-associated Micrococcus, including glycosylated glycerolipid [13][14], cyclic peptide [15], xanthone glycoside [16], and halogenated diphenyl ether [14]. Until now, however, no natural products are known from coral-associated Micrococcus. As a part of our

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• photoswitch into the backbone of gramicidin S (1, GS), which is an intrinsically biostable cyclic peptide, as exemplified by one of our first prototypes compound 2 (Figure 1C). This natural antimicrobial agent has an amphipathic structure, whose functional mechanism is attributed to the permeabilization of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• )-135 instead of the allyl residue opened the way to synthesis of ʟ-(+)-furanomycin and its 5'-epimer. MeBmt (2S,3R,4R,6E)-139 is a nonproteinogenic amino acid found as a constituent of the naturally occurring cyclic peptide cyclosporine currently in medical use as immunosuppressant [89]. Syntheses of

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• degassed 1,2-dimethoxyethane (DME)/EtOH/H2O (9:9:2) under microwave irradiation at 120 °C for 30 min (Scheme 2). An aliquot of the resulting resin 5 was cleaved, and HPLC and mass spectrometry analysis of the crude reaction mixture revealed the formation of the biaryl cyclic peptide 6 in 18% purity. Mass

• –Miyaura reaction of 10 was carried out using the same conditions for the macrocyclization of resin 7. Mass spectrometry analysis of the crude reaction mixture from cleavage of an aliquot of the resulting 11 revealed the formation of the expected biaryl cyclic peptide 12 in 21% HPLC purity. Selective Boc

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• signal data. Compounds A and B generated by alkaline hydrolysis This toxin is composed of a cyclic peptide formed by an ester linkage between the OH of Thr18 and the CO2H of Val22. Figure S15 (Supporting Information File 1) shows the primary structures of cichopeptin A and B [14], syringopeptin 22-A and

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• important demonstration of the protocol is the preparation of the unusual amino acid component of the bioactive cyclic peptide Chap-31. Keywords: α-amino acid; catalysis; cross metathesis; hydroxamates; Introduction Cross-metathesis reactions (CM) have rapidly grown [1][2][3] to be a reliable method for

• ] and the didehydrohydroxamate TSA (2) [24], display useful anticancer properties through inhibition of histone deacetylase enzymes (HDAc) and are used as FDA-approved drugs. Similarly, the cyclic peptide Chap-31 (3) [25] with a terminal hydroxamic acid residue has shown promising anticancer activity

• synthesis of the unusual amino acid component of the important anticancer cyclic peptide compound Chap-31, we attempted the cross-metathesis reaction of N-benzyloxyacryl amide 5 with the homoallylglycine derivative 4k (Table 1, entry 11) and the bis-homoallyl glycine derivative 4l (Table 1, entry 12) [32

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• ) reagent FPID and (4-MeOC6H4)3P was successfully applied to solid-phase peptide synthesis and cyclic peptide synthesis. Four peptides with biological activities were synthesized through SPPS and the bioactive cyclic heptapeptide pseudostellarin D was obtained via solution-phase peptide synthesis. It is

• worth noting that FPID can be readily regenerated after the peptide coupling reaction. Keywords: cyclic peptide; FPID; hypervalent iodine(III) reagent; recyclable; solid-phase peptide synthesis (SPPS); Introduction The amide bond is one of the most fundamental functional groups in organic chemistry

• peptide synthesis and cyclic peptide synthesis. Results and Discussion At the beginning of our study, we tried to utilize the system of FPID/(4-MeOC6H4)3P in the solid-phase peptide synthesis (SPPS). SPPS has been widely employed in peptide synthesis since its first report by Merrifield in 1963 [30][31

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• payloads to brain malignancies [78][79]. Cyclic peptide variants have been developed for the RGD peptide motif, reported above. The most commonly used cyclic peptide is iRGD (CRGDKGPDC), a 9-amino acid cyclic peptide, with tumor tissue penetration activity [80]. iRGD initially binds to αVβ3 and αVβ5

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• , indicating that the central cyclic peptide core probably has an expanded ring conformation. Garcia-Hartjes et al. synthesised and evaluated the GM1os linked calix[5]arene molecule 31 as shown in Figure 12, and found that compound 31 displayed 100,000 times more potency as compared to GM1os derivatives having

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• -adrenergic receptor [31], ligands can occupy more than one binding site along the binding path. In the case of vasopressin, a cyclic peptide hormone, the simulations revealed three different sites, the conventional orthosteric one that activates the ligand, an “intermediate” and a “vestibule” site

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• tricyclic skeleton that bears a newly formed pyrrolidine, similar to proline. The post-translational dimethylallylation of two tryptophan residues of a cyclic peptide, kawaguchipeptin A, from cyanobacteria has also been reported. Interestingly, the modified tryptophan residues of kawaguchipeptin A have the

• with other biosynthetic studies on prenylated cyanobactins, KgpF functions at the end of the biosynthesis, and recognizes two tryptophan residues in the precursor cyclic peptide to form kawaguchipeptin A. In contrast to typical post-translational modifications, a specific amino acid motif adjacent to

• the core peptide sequence for directing KgpF is unlikely to be required. In addition, the prenylation reaction by KgpF does not seem to need a specific amino acid motif within the core cyclic peptide, because there is no similarity between the sequences surrounding the two tryptophan residues (PWL and

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• report well-defined tetravalent mannose glycoconjugates on a cyclic peptide which show specific binding with concanavalin A [29]. Further, the ternary type-II polyproline helix is used for the structurally defined presentation of sugar units [34], and similarly the β-peptides provide a suitable