New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• natural products, despite their notable biological activities. Reactivity-based screening is an emerging strategy in natural products discovery, in which chemical probes are used for the specific detection of the unique functionality of interest in crude metabolites [5][6]. The reactions usually

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• diterpenes with characteristic isocyano, isothiocyano, and formamido functionalities [2][3][4][5]. Many of these secondary metabolites merit further investigation due to their intriguing structural diversity and wide spectra of biological activities ranging from antifeedant, antifouling, and cytotoxic to

• antibiotic effects [3][5][6]. Acanthella sponges have thus attracted much attention from marine natural products chemists and pharmacologists. The title animal is the most chemically studied species among the Acanthella sponges. Till now, more than 100 secondary metabolites belonging to sesquiterpenoids and

• diterpenes [7][8], alkaloids [9], and steroids [10], have been isolated and characterized. In connection with our continuing studies of Chinese marine invertebrates to search for novel and bioactive secondary metabolites, we have recently studied the sponge A. cavernosa collected from Ximao Island of Hainan

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• University, Johannisallee 21–23, 04103 Leipzig, Germany 10.3762/bjoc.18.72 Abstract Aromatic prenylated metabolites have important biological roles and activities in all living organisms. Compared to their importance in all domains of life, we know relatively little about their substrate scopes and

• prenyltransferase; Introduction Marine bacteria harbor an enormous potential to produce structurally diverse natural products, including prenylated aromatic metabolites [1][2]. Prenylation of metabolites most often confers increased biological activities due to enhanced lipophilicity, solubility, and improved

• spectrometer equipped with a Bruker Cryoplatform with chemical shifts given in ppm (δ). Prenylated aromatic metabolites are involved in cellular processes like cell respiration (coenzyme Q10), cell growth and survival (menaquinone MK-4), photosynthesis (chlorophyll a), oxygen reduction (heme O), and

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan 10.3762/bjoc.18.71 Abstract Endoperoxide natural products are widely distributed in nature and exhibit various biological activities. Due to their chemical features, endoperoxide and endoperoxide-derived secondary metabolites have attracted keen

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• -3α,12α,16α-triol (6) [15], 3-epimaslinic acid (7) [18], oleanolic acid (8) [19], and ursolic acid (9) [20]. To find potential antineuroinflammatory, neurotrophic, and cytotoxic secondary metabolites from G. hederacea var. longituba, the isolated compounds (1–9) were evaluated for these biological

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• Trichoderma citrinoviride produces structurally diverse secondary metabolites including diterpenes [1][2], alkaloids [3], sorbicillinoids [4][5], long chain alcohols [6], and cyclonerane sesquiterpenes [7]. Some of them display antibacterial [1][2][7], cytotoxic [3], anti-inflammatory [4], and antimicroalgal

• [7] activities. Based on these data, the investigation of secondary metabolites from this fungus is still limited. In our ongoing search for antimicrobial secondary metabolites from soil-derived fungi, T. citrinoviride PSU-SPSF346 was isolated from a soil sample collected from the Sirindhorn Peat

• configurations at C-5, C-6, C-7, and C-10 of compound 2 were proposed to be 5S, 6S, 7S, and 10R identical to those of the co-metabolites 4 and 5. The absolute configuration at C-4 was thus assigned to be R. Therefore, compound 2 is a rare bicyclic sesquiterpene. The isolated compounds 1 and 3–6 with sufficient

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• ; quinone; synthetic platform; vitamin K; Introduction Naphthoquinones belong to the chemical family of quinones and are widely present in synthetic and natural products (Figure 1). In nature, quinones are biosynthesized as secondary metabolites by various organisms, from simple single-celled

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• metabolites with great variety and bioactivities. Previous chemical studies on soft corals Lobophytum, widely distributed in the world, resulted in the identification of lobane diterpene [1], cembranoids [2], and biscembranoids [3] with different bioactivities. Moreover, structurally specific steroids

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• iron-chelating properties of the retrieved metabolites were evaluated in a chrome azurol S assay. Keywords: actinomycete; amamistatin; Nocardia; siderophore; structure elucidation; Introduction Iron is known to easily interconvert between a reduced ferrous (Fe2+) and an oxidized ferric state (Fe3

• Nocardia as a whole is considered to be a rich source of bioactive secondary metabolites, including many structurally diverse siderophores [6]. Up to now, however, chemical studies in this taxonomic group mainly focused on pathogenic strains. In the present study we explored siderophore production in the

• fermentations of N. altamirensis DSM 44997 were then carried out to secure sufficient material of the responsible iron chelator(s) for isolation and structure elucidation. The metabolites secreted into the culture broth were recovered post fermentation with the adsorber resin XAD-7. After removal of the culture

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• diversity of the secondary metabolites from the genus Wikstroemia. Keywords: coumarin glucosides; flavonoids; lignans; structure elucidation; Wikstroemia nutans; Introduction The genus Wikstroemia (Thymelaeaceae) contains approximately 62 species, which are widespread throughout the subtropical regions of

• Asia and Oceania [1]. Nineteen species of the genus Wikstroemia are found to be domestic in China, such as W. nutans, W. indica, and W. canescens [2]. Previous investigations have not only reported diverse secondary metabolites from the genus, but also promising pharmacological activities of the

• ) [25] (Figure 1) by comparison to literature data. In addition, compounds 2, 3, 8, and 11 were isolated for the first time from the genus Wikstroemia. Biological activity Considered naturally occurring glycosides of phenolic metabolites usually exhibit anti-inflammatory activity in literature [26

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

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

• . They instead harbour diverse and abundant microbes on their body surface or in the tissues [2][3] and are believed to utilize secondary metabolites from the symbionts as protectants from attacks by predators, competitors, or pathogens. The ecological functions as such make marine microorganisms an

• metabolites from Gram-negative bacteria are still quite limited, despite the predominance of this group in the marine environment [10][11]. The genus Tenacibaculum belongs to the family Flavobacteriaceae within the phylum Bacteroidetes. Members of this genus are Gram-negative, aerobic, motile by gliding, and

• available on the secondary metabolites from this genus [17][18]. In our continuing search for bioactive compounds from underexplored marine bacteria [19][20][21], a Tenacibaculum strain, isolated from a stony coral, was found to produce three metabolites, which turned out to be new cytotoxic hydroxamate

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• enzyme human carboxylesterase (hCE1) that cleaves carboxylic esters. This enzyme functions in the detoxification metabolism of carcinogenic and mutagenic organic compounds, converting them into nontoxic metabolites. This compound served as inspiration for Hatfield and co-workers [84], who proposed the

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• .17.203 Abstract A genome mining survey combined with metabolome analysis of publicly available strains identified Couchioplanes sp. RD010705, a strain belonging to an underexplored genus of rare actinomycetes, as a producer of new metabolites. HPLC-DAD-guided fractionation of its fermentation extracts

• Streptomyces, are especially noted, accounting for more than 800 metabolites of actinomycetes origin [11], which include the antiinfective aminoglycoside gentamicin [13], antidiabetic glycoside acarbose [14], glycopeptide antibiotic teicoplanin [15], enediyne antitumor component of drug-antibody conjugate

• metabolites of Pseudosporangium sp. RD062863, a strain available at the culture collection of the Biological Resource Center, National Institute of Technology and Evaluation (NBRC) [20], and discovered a novel cyclopeptide pseudosporamide along with three new oligomycin-class polyketide [21]. In addition, the

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• relationships in this chemotype. Keywords: acyl Pictet–Spengler reaction; alkaloids; antiproliferative activity; benzyltetrahydroisoquinolines; ion channels; protective group; total synthesis; Introduction The benzylisoquinoline alkaloids are a large and diverse class of plant secondary metabolites including

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• hepatotoxicity and neurological effects on livestock and humans [1][2]. The less commonly encountered 2,3-dihydro-1H-pyrrolizine framework occurs in the butterfly metabolites danaidal (2) and hydroxydanaidal (3) [3], as well as in plant alkaloids such as loroquin (4) [4] and the recently characterized

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• microbial sources led to the isolation of Pseudomonas sp. UIAU-6B from sediments collected from the Oyun river in North Central Nigeria. Herein, we report the isolation and structure elucidation of seven secondary metabolites including five new (1–5), and two known phenolic siderophores (6 and 7) [28][36

• secondary metabolites 1–5 including pseudomonin A–C (1–3) and pseudomobactins A and B (4 and 5). The two known compounds, pseudomonine (6) and salicylic acid (7) were also isolated as the major constituents of the extracts and their structures were determined by analysis of HRESIMS, 1D and 2D NMR data (see

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• A. fordii have shown Epstein–Barr virus activation effects and an enhancement of HTLV-I-induced colony formation of lymphocytes [8]. As an ongoing search for bioactive secondary metabolites from Korean medicinal sources, we investigated the methanolic extract of the twigs of A. fordii which resulted

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• marine environment is now attracting attention as a promising source for actinomycetes potentially producing new secondary metabolites [4][5]. Indeed, a large number of pharmaceutically worthy new compounds has been found from marine actinomycetes in various niches including sediments, sea water, marine

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• metabolites. The genetic potential for the production of secondary metabolites in fungi is high and numerous potential secondary metabolite gene clusters have been identified in sequenced fungal genomes. Their production may well be regulated by specific ecological conditions, such as the presence of

• microbial competitors, symbionts or predators. Here we exemplarily summarize our current knowledge on identified secondary metabolites of the pathogenic fungus Aspergillus fumigatus and their defensive function against (microbial) predators. Keywords: amoeba predation; Aspergillus fumigatus; fungal ecology

• , physiological adaptations and chemical defence mechanisms to optimize their living conditions and resist competitors, parasites and predators [3][4][5]. These bioactive compounds are often considered as secondary metabolites (SM) which are involved in communication, symbiotic interactions, pathogenicity or

Analogs of the carotane antibiotic fulvoferruginin from submerged cultures of a Thai Marasmius sp.

• Birthe Sandargo,
• Leon Kaysan,
• Rémy B. Teponno,
• Christian Richter,
• Benjarong Thongbai,
• Frank Surup and
• Marc Stadler

Beilstein J. Org. Chem. 2021, 17, 1385–1391, doi:10.3762/bjoc.17.97

• methodology is still not available. As of 2006, the family forms a sister taxon to the Omphalotaceae within the suborder of Marasmiineae (Agaricales) [2][3]. Among Basidiomycota, the Marasmiineae are most famous for their abundant chemical diversity. Metabolites with various bioactivities described from

• characterization. Results Structure elucidation of the secondary metabolites 2–6 Preparative HPLC of the supernatant crude extract of a submerged cultivation of Marasmius sp. strain MFLUCC 14-0681 in ZM½ media led to the isolation of six carotane sesquiterpenoids, fulvoferruginins A–F (1–6, Figure 1). The first

• fulvoferruginins A–F (1–6), aside from the known antifungal activity of fulvoferruginin (1), no other antimicrobial activities were observed (Table S2 in Supporting Information File 1). All metabolites were also tested against the murine fibroblast cell line L929 and the cervix carcinoma cell line KB3.1. While all

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• distributions of metabolites and identifying specific symbiotic bacteria. Keywords: algae; AP-SMALDI; ectoine; holobiont; high-resolution mass spectrometry; mass spectrometry imaging; marine bacteria; Ulva; Introduction In intertidal zones with high temporal and spatial ecosystem variations, bacteria and

• specialised metabolites involved in host–bacteria interactions. In our study, comparative metabolomics using atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionisation high-resolution mass spectrometry (AP-SMALDI-HRMS) enables the identification of specialised metabolites of the

• profile fingerprint matching [26][27][28]. Our research combines cutting-edge laser scanning microscopy and high-resolution mass spectrometry to uncover Ulva/bacteria interactions and specialised metabolites at the microscale level. In this study, we demonstrate that the chemosphere of U. mutabilis

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• synthetic methods for secosteroids is wide. However, usually these are multistep sequences exploiting toxic oxidants. Marine invertebrates are a rich source of oxidated and highly functionalized steroidal metabolites, including secosteroids. Since the first isolation of 9,11-secosterol from

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• , indicating that this strategy was not suitable for the synthesis of γ-phosphonodepsipeptides (Scheme 13) [28]. Folylpolyglutamate synthetase catalyzes an ATP-dependent ligation reaction. The reaction results in the synthesis of poly(γ-glutamate) metabolites of folates and some antifolates. Three γ

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• changes and other types of stress. For example, in exponentially growing E. coli, the intracellular concentration of proline was determined as 3.9 × 10−4 mol⋅L−1. This data ranks proline as the 41st in the list of metabolites and as the 9th among the amino acids coded into proteins [60]. The two main