Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• observed (yield = 72%) with analysis by chiral HPLC revealing no erosion of the enantiomeric ratio (er = 99:1). At this stage, the suitability of BT-SCF3-mediated deoxyfluorination for the one-pot formation of peptide linkages between amino acids was investigated (Scheme 3). Treatment of N-Boc-valine under

• under mild and operationally simple conditions while peptide coupling between two amino acids could be efficiently conducted using the longer-chain perfluoroalkyl reagent BT-SC5F11. Mechanistic studies revealed that each equivalent of the benzothiazolium reagent can feasibly generate two equivalents of

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• . NNG is a non-proteinogenic amino acid, similar to other such N–N containing compounds such as piperazic acid and hydrazinoacetic acid [43]. These precursors are incorporated into larger NPs by non-ribosomal peptide synthases or polyketide synthases, and NNG may have a similar fate [44][45]. Another

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• Yue Ma Lorenzo Persi Yoko Yamakoshi Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland 10.3762/bjoc.20.71 Abstract With the aim of developing biocompatible and water-soluble C60 derivatives, three types of C60–peptide conjugates consisting

• successfully provide C60–peptide conjugates with one C60 and two peptide anchors as water-soluble moieties. Among three C60–peptide conjugates prepared, C60–oligo-Lys was soluble in water at neutral pH, and C60–oligo-Glu was soluble in buffer with a higher pH value, but C60–oligo-Arg was insoluble in water and

• example, as a photosensitizer in photodynamic therapy. Keywords: biomaterial; fullerene; peptide; water-soluble; Introduction Since the seminal discovery in 1985 by Kroto, Smalley, Curl, and co-workers [1], fullerenes, specifically buckminsterfullerene C60, have intrigued the scientific community. The

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• compound is made through a trans-AT polyketide synthase–non-ribosomal peptide synthase (PKS-NRPS) hybrid [9][10]. Instead of using the classical domain organisation KS-AT-ACP with AT domains integrated into the PKS, trans-AT PKSs utilize discrete ATs that are not an integral part of the PKS, but rather

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• and multifunctional enzymatic assembly, nonribosomal peptide synthases (NRPS), polyketide synthases (PKS), and hybrid NRPS/PKS systems, which are organized into sets of functional domains known as modules and function through a similar mechanism [9][10][11][12]. Each NRPS module is composed of three

• attention is given to the strategies of mimics formation to demonstrate how biocatalysis provides an elegant link between chemistry and biology. Review Macrocyclic peptides Since first being reported in the 1960s [26], solid-phase peptide synthesis (SPPS) has been an invaluable tool for preparing numerous

• -workers developed an elegant chemoenzymatic route in 2000 [36]. The synthesis commenced to construct linear decapeptide 2 by global SPPS method on 2-chlorotrityl resin. After coupling 2 with N-acetylcysteamine (NAC, 3), the mimic of peptide-S-PCP, peptide-SNAC 4 was prepared. When incubated with purified

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• draft genome sequence of the H002 strain identified the variochelin biosynthetic gene cluster (var), which encodes PKS (polyketide synthase) and NRPS (non-ribosomal peptide synthetase) genes. Finally, the siderophores isolated in this study exhibited antibacterial activity against several bacteria

• siderophores 1–5 share the same amino acid residues containing a combination of two hydroxamates and α-hydroxycarboxylate functional groups, which are capable of forming a photoreactive Fe(III) complex [5]. The common peptide headgroup with the additional repertoire of hydrophobic tails at the N-termini (3–5

• by diamonds. EIMS of DMOX derivatized free fatty acids derived from variochelins C–E (3–5). (a) 3, (b) 4, and (c) 5. (a) Plausible biosynthetic pathway of variochelin A–E (1–5). The circles represent domains: A: adenylation domain, C: condensation domain, PCP: peptide carrier protein, E

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• owing to their wide applications in medicinal chemistry [1][2][3][4][5]. γ- and ε-AA derivatives are widely distributed in peptide natural products, bioactive molecules, and drugs, such as pregabalin, baclofen, ε-aminocaproic acid and lysine (Scheme 1a) [6][7][8][9][10][11][12]. The number of reported

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• treatment of acute severe pain) [29] and an investigational drug NOP-1A (a ligand for the nociceptin/orphanin FQ peptide (NOP) receptor which is thought to be involved in several central nervous system disorders such as anxiety, depression, drug abuse, and seizures) [30]. A wide range of biological

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• (SORHA), Triticum aestivum (TRZAS), and Zea mays (ZEAMX). LpFAT A expression and purification: The fat a03 gene from Lemna paucicostata, in which the N-terminal amino acids representing the chloroplast transit peptide were replaced by an N-terminal 6xHis-tag, was cloned into a pET24 vector [3]. The LpFAT

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• University, Sakyo, Kyoto 606-8501, Japan 10.3762/bjoc.20.39 Abstract The adenylation (A) domain is essential for non-ribosomal peptide synthetases (NRPSs), which synthesize various peptide-based natural products, including virulence factors, such as siderophores and genotoxins. Hence, the inhibition of A

• synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors. Keywords: adenylation domain inhibitor; gramicidin S synthetase; natural product; nonribosomal peptide; nonribosomal peptide synthetase

• biosynthesis by using small molecules can help to elucidate their natural functions and their potential as therapeutic targets. NRPs are synthesized by large, versatile, and multifunctional proteins called nonribosomal peptide synthetases (NRPSs), which are composed of multiple modules and subdivided domains

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

• 2 was determined by Marfey’s method. A biosynthetic gene cluster (BGC) encoding unguisins B and J was compared to characterized BGCs in other Aspergillus sp. Since the unguisin family of heptapetides incorporate different amino acid residues at different positions of the peptide, the A and C domains

• of the UngA NRPS were analyzed in an attempt to understand the lack of substrate specificity observed. Keywords: adenylation domain; condensation domain; fungal non-ribosomal peptide synthetase; heptapeptide; unguisin biosynthesis; Introduction Unguisins are a small family of fungal cyclic

• small peptides [3][4][9], however, unguisin A has been shown to bind a series of anions [10]. Recently the biosynthesis of unguisins A and B from Aspergillus violaceofuscus CBS 115571 was reported [5]. A seven module non-ribosomal peptide synthetase (NRPS; UngA) was heterologously expressed in

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• hexa-His tag, cleavable by TEV (Tobacco etch virus) protease. Despite the presence of the DsbC signal peptide, we did not observe periplasmic localization, and all proteins were instead purified from the cytoplasm. Ni-NTA affinity chromatography followed by TEV protease cleavage of the fusion construct

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• applications due to their improved solubility in aqueous systems. Assembly is achieved by integrating distinct carbohydrate, peptide, and polyprenyl phosphate building blocks. This modular synthetic method allows for the strategic substitution of constituent building blocks at different synthetic stages and

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• chromophores, is the preferred method for stoppering. Accordingly, Li et al. synthesized a rotaxane 44 terminated using push–pull chromophores by incorporating concise peptide and DCNQ moieties and employing the threading–stoppering method (Scheme 16). In 44, the rod moiety and macrocycle feature short peptide

• substructures. Consequently, the macrocycle was tethered to the peptide segment through amide–amide hydrogen bonding, and 44 was obtained with 30% yield. The generation of 44 was accompanied by the formation of the corresponding free thread with 62% yield, resulting from the reaction between the thread

• yield for the ring-formation process was modest at 5% (see Scheme 16) [121][122]. The macrocycle in 46 was observed to engage with the peptide segment in low-polarity solvents. In contrast, 1H NMR analysis suggested that the macrocycle disengaged from the peptide segment and relocated along the alkyl

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• affect its pharmacological properties and metallophoric potential against copper(II) when compared to the unsubstituted counterpart. Nevertheless, the bioinspired compound was still able to reduce oxidative stress and affect the aggregation of the amyloid-β peptide, related to pathophysiological events

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• great structural variability such as polyketides, terpenoids, polyketide synthase–nonribosomal peptide synthetase (PKS–NRPS) alkaloids, and cytochalasins, which have been considered as taxonomic markers of the genus [7][8][9][10]. However, it is worthwhile to mention that the name Phomopsis should no

Correction: Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 1370–1371, doi:10.3762/bjoc.19.97

• , Shenzhen University, Shenzhen 518060, PR China Department of Pathogen Biology, Health Science Center, Shenzhen University, Shenzhen 518060, PR China 10.3762/bjoc.19.97 Keywords: arthropod; iNOS; Kronopolites svenhedini (Verhoeff); non-peptide small molecules; The structure of compound 1 of the original

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• unique catalytic behavior [89]. However, there are only a few examples of cobalt catalysis in CDC reactions. Limited by the activity of Co catalysts, there are few examples of Co-catalyzed reactions involving ether C(sp3)–H bond activation. The Co-catalyzed C(sp3)–C(sp3) CDC of glycine and peptide

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• scale [19], and linkers [20][21] affect the overall yield of solid phase peptide synthesis (SPPS). In the past decades, several supports and linkers have been developed and commercialized for SPPS, enabling a wide range of applications. Solid supports are available with different linker loadings, with

• low loading (0.1–0.2 mmol/g) being beneficial to avoid aggregation of long peptide sequences, and high loadings (0.4–0.5 mmol/g) advantageous for more efficient syntheses [21]. Herein, we systematically investigate how variations in linker type, resin loading, and reaction scale influence the

• some peptide sequences [18]. Moreover, high-loading supports might result in inefficient UV cleavage due to quenching. These four supports were studied in AGA experiments performed at 15 and 30 µmol reaction scales. While AGA is commonly performed at a 15 µmol reaction scale, a larger reaction scale is

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• antibacterial acitivity against resistant S. aureus strains. It is also an inhibitor of the enzyme peptide deformylases (PDFs). The synthesis comprised the reaction between the highly substituted hydroquinone 142 and dehydroalanine 143 in the presence of chiral phosphoric acid P7 as catalyst to prepare

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• methods. Selected compounds were evaluated for their biological properties against a mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2 in RAW264.7 cells. Keywords: arthropod; iNOS; Kronopolites svenhedini (Verhoeff); non-peptide small molecules; Introduction The millipede (class

• . In our studies of arthropods over the years, we have found that non-peptide small molecules play a significant role in chemical structures and biological activities [11][12][13][14][15][16]. In examining the chemical constituents of the millipede K. svenhedini, the focus was directed toward non

• -peptide small molecules, leading to the isolation of six new and three known compounds (Figure 1) from its extract. These structures were determined by 1D and 2D NMR spectra and the experimental and calculated electronic circular dichroism (ECD) spectra. The six new compounds have been named kronopoone A

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• target compounds, which contained two pharmacophores – [1,2-a]pyridine (1H-imidazo[1,2-b][1,2,4]triazole) and peptidomimetic moieties – were evaluated for their antibacterial activity and exhibited a weak effect. Drugs possessing imidazo[1,2-a]pyridine unit. Drugs possessing peptide unit. Diversity of

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

• several well-known natural products with interesting biological properties, such as the glycopeptide antibiotics vancomycin and teicoplanin [5] or feglymycin [6], a 13mer peptide which contains nine α-arylglycines in its backbone. α-Arylglycine derivatives are used in the production of important drugs

• decrease of the isolated yields. As already demonstrated in our previous work, the Pbf-protected arylglycine products can be directly used as building blocks for peptide synthesis [22]. Finally, we utilized our method for the preparation of a protected version of p-hydroxyphenylglycine (Scheme 5), a common

• is an improved extension of our pervious protocol with arylboronic acids and provides access to enantioenriched α-arylglycines with an improved substrate diversity. It can be used for the direct synthesis of peptide-like building blocks, which can find direct application in the total synthesis of

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• fluorescence response. Compounds that consisted of pyrrole-guanidine attached to larger aryl moieties (pyrene and phenanthridine) bind to the human DPP III enzyme [17]. Pyrene–cyanine conjugates connected with a rigid triazole-peptide linker were designed and synthesized in our group and showed a strong pyrene

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• as potential inhibitors of cathepsins. The phosphorus atom by default should mimic the tetrahedral intermediate, but this role may also be played by the hydroxy group present in hydroxyphosphonates, which mimic the carbonyl carbon in the peptide bond by forming a hydrogen bond with the amino group of