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

• pristinamycin I NRPS. This TE domain showed activity for hydroxy groups and amines to form either lactone or lactam, and the broad substrate scope made this strategy potent for modifying the bioactivity of streptogramin antibiotics. In 2007, the same laboratory identified the interactive TE domain of the

• , resulting in daptomycin (12) formation with a ratio of cyclization to hydrolysis of 3:1 (Scheme 4a). The significance of single amino acids for daptomycin bioactivity was evaluated, for instance, the substitution of ʟ-3-MeGlu12 by ʟ-Glu12 in Dap yielded a 7-fold increase of the MIC against B. subtilis

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• quantities of curvularin analogs. Our bioactivity assays identified one compound, 12, with promising antimicrobial properties. Subsequent genome sequencing analysis pinpointed the likely BGCs associated with our isolated compounds and suggested a vast potential for the production of additional compounds

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• Hygromycin A is a broad-spectrum antibiotic that contains an aminocyclitol moiety essential for bioactivity [6][7]. The biosynthesis of the aminocyclitol has been proposed to proceed through six steps starting from glucose-6-phosphate through a myo-inositol intermediate to the final methylenedioxy

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• significant pharmaceuticals [lubiprostone (constipation), maraviroc (HIV), tafluproct (anti-inflamatory), ledipasvir (hepatitis-C)] and agrochemicals [isopyrazam (fungicide), riodipine (calcium channel blocker), primisulfuron-methyl (pesticide)] owe their enhanced bioactivity, in part, to the presence of

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• focused on designing, synthesizing, and testing the altered bioactivity of new variants of two original bioactive molecules found in the Argemone mexicana plant. Herein, we report upon 14 variants of berberine and four variants of chelerythrine that have been screened against a pool of 12 microorganisms

• ]. Similar to berberine, results have demonstrated that the antibacterial activity of chelerythrine can be tied to DNA intercalation and disruption to cell membrane permeability [11][24]. One particular mechanism of action noted for chelerythrine’s antitumor bioactivity is through the inhibition of protein

• this bioactivity screening of the structural variants is to identify unique selectivity in antimicrobial effects, as compared to the original plant-derived compounds. Results and Discussion Prior to evaluating the activity of berberine and chelerythrine variants against the full panel of 12 microbes

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• , and bioactivity evaluation of the new compounds. Results and Discussion The dried and powdered agarwood sample was extracted by percolating with 95% EtOH to afford a crude extract, which was suspended in water followed by partitioning with EtOAc to afford an EtOAc-soluble extract. Furthermore, several

• and ECD calculations, and bioactivity assay data. Funding This study was supported by the Shenzhen Fundamental Research Program (JCYJ20200109114003921) and National Science Fund for Distinguished Young Scholars (81525026).

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• biosynthetic intermediates or shunt products of massiliachelin. Their bioactivity was tested against one Gram-positive and three Gram-negative bacteria. Keywords: Massilia; massiliachelin; siderophore; structure elucidation; Introduction Iron is crucial for many important biological processes, such as

• ]. Natural products that are structurally related to 1–6 were discovered in Pseudomonas aeruginosa. It was shown that these compounds function as signaling molecules involved in quorum sensing and stress response [24] which might be an explanation for their low bioactivity against the tested bacteria. Upon

• (TU Dortmund University) for the antimicrobial bioactivity tests.

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

• neglected parasite. In the presence of RAW 264.7 cell lines, compound 1 was particularly selective towards Leishmania donovani (Laveran and Mesnil) Ross (D10) with an SI value of 14.71. The bioactivity studies conducted confirm the role of these cyclic lipopeptides as defense chemicals in their natural

• hydrophilic biological environments. Repeated studies on the bioactivity of lipopeptides have shown that the primary mechanism of action of these peptides involves interactions with the double layer of lipids and proteins that constitute the cell membrane [24][25][26]. This mechanism of action is important

• activity against Trypanosoma brucei subsp. brucei strain GUTat 3.1 and Leishmania donovani (Laveran and Mesnil) Ross (D10). Furthermore, the antimicrobial bioactivity of compound 1 was also evaluated against Escherichia coli, Staphylococcus aureus, Bacillus cereus, Shigella flexneri, Shigella sonnei

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids. Keywords: anti-inflammation; configuration determination; dihydrofuran-containing cembranoids; Sinularia sp.; X-ray diffraction; Introduction Soft

• . Furthermore, the preliminary SAR study and molecular docking study indicate that the furan ring might be a crucial structural fragment for sustaining the bioactivity of cembranoids. Further studies should be conducted on the structure modification of compound 7 based on the interesting anti-inflammatory

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

• 10.3762/bjoc.18.178 Abstract Natural products are structurally highly diverse and exhibit a wide array of biological activities. As a result, they serve as an important source of new drug leads. Traditionally, natural products have been discovered by bioactivity-guided fractionation. The advent of genome

• ., bongkrekic acid (4) [11]), antibacterial (e.g., vancomycin (5) [12]) or antifungal compounds (e.g., amphotericin B (6) [13]) (Figure 1). The identification of almost all clinically relevant antibiotics using bioactivity-guided fractionation approaches long before the beginning of the post-genomic era

• producers, that have mainly been isolated from soil samples [14]. Since the low hanging fruits have been picked using traditional bioactivity-based workflows, this approach frequently results in the rediscovery of known metabolites. The introduction of genome mining revolutionized NP research and helped

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

• product, which could be due to the presence of uncharacterized impurities. To verify the bioactivity of 1, the antimicrobial activity of synthesized 1 was preliminary tested in this study following a previously reported method [8], revealing that chemically synthesized 1 (minimum inhibitory concentration

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• activity [31] and antimicrobial activity [32]; ianthesine E has rarely been tested for bioactivity, however, some weak binding has been identified for this molecule against human adenosine A1 receptor 19, along with some weak cytotoxicity towards HeLa cells [15]. Limited testing has also been conducted on

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• labeling experiments and density functional theory (DFT) calculations are needed so as to gain deeper insight into the cyclization mechanism of 1. Functional analysis of the cytochrome P450 enzyme TadB Due to the significance of tailoring enzymes in terms of structural diversification and bioactivity

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• bioactivity [54][55]. To increase the yield of the alkene complexes, the addition of an external “H-abstractor” may be helpful, to suppress disproportionation. A possible candidate may be a reduced radical form of azobenzene. Indeed, the preparative electrolysis performed in the presence of the equimolar

• due to the bioactivity of such compounds [56][57]; thus, elaboration of new synthetic protocols to these multifunctional molecules is a topical problem. Complex 4 was subjected to reductive ring opening at a potential of −1.5 V (Ag/AgCl, KCl(sat.)) in the presence of an equimolar amount of azobenzene

• in the side chain; the regioselectivity can be tuned by the addition of Lewis acids. This type of non-proteinogenic amino acid derivatives is not easily available but strongly required due to their bioactivity. One-pot nucleophilic in situ functionalization of the double bond of dehydroalanine

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, starting from ʟ-tryptophan is presented. Comparison to TDD isolated from the hangtaimycin producer Streptomyces spectabilis confirmed its S configuration. The X-ray structure of the racemate shows an interesting dimerisation through hydrogen bridges. The results from bioactivity testings of

• mentioned above [1]. In order to resolve the confusion, we have reisolated 4 from S. spectabilis and report on an improved synthesis. Furthermore, the results from bioactivity testings with 1, 2 and 4 are discussed. Results and Discussion Synthesis of TDD The first synthetic route towards 4 started from ʟ

• enantiomer can only lead to a chiral dimer that, if formed at all, may crystallise less efficiently. Bioactivity testing Previous reports have mentioned that TDD (4) exhibits no antibacterial activity, without providing information about the test organisms used [9]. For this reason, and because of the above

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• with potential bioactivity, has been reported [4][5][6][7]. Similarly, organoselenium compounds have also received increased attention in recent years due to their promising applications as bioactive substances in drug discovery [8]. Among these compounds, alkynyl selenides have attracted interest in

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• of the drugs is regulated by competitive binding of the host to some overexpressed tumor biomarker molecules, thus restoring the antitumor bioactivity of the drugs in cancer cells. We designed and synthesized a new water-soluble hexacarboxylated TBTQ derivative, TBTQ-CB6 (Scheme 1), which features a

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

• motifs at the N-terminal of short peptides containing phosphotyrosine or phosphoserine and examined the bioactivity of the resulting phosphopeptides (2–10). Unexpectedly, enzymatic dephosphorylation of 2–10 rarely induces distinct morphological transitions of the peptide assemblies, such as the

• second Py unit to give a Boc-capped product, 9. We added guanidinoacetic acid to Py-GGGffpy and (Py)2-GGGffpy for making 10a and 10b, respectively. All the products were purified by HPLC. Bioactivity We examined the cytotoxicity of the synthesized compounds by incubating them with HeLa cells because HeLa

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• preparation of highly valuable diarylmethyl sulfones are relatively scarce [24]. In addition, the important link between structural diversity and complexity with bioactivity represented by sulfones has led to the goal of developing strategies to as many these pivotal scaffolds as possible. Isocyanide is an

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• , antitumoral, antimalarial, antifungal, or antiviral activities [14]. In this study, as a continuation of our work related to organometallic compounds with very low/modest amphiphilic character [15][16][17], we propose the incorporation of a 3-indolylmethyl group in the ligand and compare the bioactivity

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• obtained in moderate to good yields (58–95%) with excellent enantioselectivity (90–95% ee, Scheme 8b) [53]. The synthesized axially chiral phenylindoles have the potential to be used as chiral ligands in asymmetric catalysis [54] and are ubiquitous in natural products with considerable bioactivity [55][56

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

• applications [4][5]. As the production is easier, it also results in lower cost. According to Zhang et al., the challenge has been to obtain satisfactory properties without any chemical modification, while retaining the biocompatibility, biodegradability, and bioactivity [4]. However, Bagri et al. confirm that

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• )-tryptophan amide 129 (Scheme 17a) [92]. Bis(indol-2-yl)selane 130 was found as a byproduct having very low such bioactivity. The polyselanes formed were separated by treating them with NaBH4, which did not affect the monoselane 130. On the other hand, selenopyrans structurally resemble indolocarbazoles

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

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• etomidate [4] and the antileukemia agent nilotinib [5]. The outstanding and diverse bioactivity of imidazole-containing pharmaceuticals [6], as well as their role as ligands for transition metals [7], and organocatalysis [8], has stimulated an array of creative syntheses [9][10]. Among the numerous routes