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

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• polycavernosides. Keywords: macrolide glycoside; marine cyanobacterium; marine natural products; polycavernosides; terminal alkyne; Introduction In 1991, an outbreak of food poisoning caused by a species of red algae known as ‘Polycavernosa tsudai’ occurred in Guam, which resulted in killing of three people. Two

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• , demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids. Keywords: biosynthesis; meroterpenoids; natural products; pathway engineering; terpene cyclases; Introduction Meroterpenoids are a class of natural products partially biosynthesized from a terpenoid

• of “unnatural” natural products by rationally combining the biosynthesis of DMOA- and 5-MOA-derived meroterpenoids. To the best of our knowledge, our study provides the first examples in which meroterpenoid species are generated via the direct dearomatizing prenylation of 5-MOA. Despite its

• simplicity, this strategy yielded six previously unreported meroterpenoids, demonstrating the effectiveness of our methodology in discovering new natural products. Given the increasing elucidation of fungal meroterpenoid pathways in recent years, similar approaches could be applied to other meroterpenoid

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

• terpene alkaloid; natural products; Penicillium; structure elucidation; Introduction Penicillium, a genus within the Ascomycota phylum, is a type of critical saprophytic fungus with over 400 strains identified in diverse environments such as mountains, oceans, and the human gut [1]. After the first

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

• noticed that some other enzymes from this PFAM are also paired with aminotransferases to generate amino sugars found in natural products [25][26], so we looked to see if aminotransferases are commonly found by PF01408 sequences. We observed three separate aminotransferase PFAMs near many of the PF01408

• pathways. Genome neighborhood analysis shows that many PF01408 sequences can be found near known biosynthetic enzymes, aminotransferases, and resistance genes suggesting that these enzymes may be promising candidates for targeted gene mining strategies to discover novel natural products. Experimental

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• Zhiyang Quan Takayoshi Awakawa RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan 10.3762/bjoc.20.50 Abstract Meroterpenoids are hybrid compounds that are partially derived from terpenoids. This group of natural products displays large structural diversity, and many

• for the design of biosynthetic machineries to produce a variety of bioactive meroterpenoids. Keywords: αKG-dependent dioxygenases; enzyme engineering; fungal meroterpenoids; synthetic biology; terpene cyclases; Introduction Meroterpenoids are complex natural products with intricate skeletal

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

• modern drug design [1][2]. They are known to promote higher success rates, when targeting three-dimensional protein molecules [3][4]. Furthermore, a wide variety of spirocyclic fragments can be spotted in natural products [5]. The aspects mentioned unveil the development of synthetic methodologies

• antagonist 7 [33], and aldosterone synthase inhibitor 8 [34]) as well as natural products (e.g., new alkaloids deoxytryptoquivaline and deoxynortryptoquivaline from fungus Aspergillus clavatonanicus identified as natural cardiomyocyte-protective agents against cold ischemic injury [35] and possible natural

• )ethanol. In the latter case, the predominant process was found to be the base-promoted migration of the C=C bond of the arylidene fragment into the cycle. Examples of biologically active compounds and natural products based on THF/THP spiro-conjugates with pyrrolidine rings. DAS spirocyclizations reported

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• Actinomycetes are well-known as the main producers of bioactive compounds such as antibiotics, anticancers, and immunosuppressants. Screening of natural products from actinomycetes has been an essential part of several drug discovery programs. Finding such novel biologically active metabolites is immensely

• important because of their beneficial health effects. Recently, the discovery of new compounds has diverted attention to rare actinomycetes, since they are rich sources of natural products. In this study, a collection of rare actinomycetes at Kitasato University has been screened for potential novel

• reaction [9]. This technique has been used to find several new compounds from actinomycetes [10][11][12][13]. In the course of our PC screening for new natural products from rare actinomycetes, Saccharopolyspora sp. KR21-0001 produced a new compound 1, whose physicochemical properties, accurate mass and UV

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

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• bis(indolyl)methanes (BIMs) have found increased use either as standalone medicine or in combination with other compounds for their bactericidal and fungicidal properties (Scheme 1). BIMs are natural products that are found in certain marine species of sponges and have also been isolated from

• highest fungicidal activity [11]. Brønsted or Lewis acid catalysis – conventional synthetic methods The indole moiety is part of many natural products, agrochemicals, and pharmaceuticals. In medicinal chemistry, indole and its derivatives are considered important compounds, since they exhibit valuable

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• -derived NHPI esters has found application in the total synthesis of natural products, including the plant metabolite denobilone A and the highly oxidized dibenzocyclooctadiene lignans heteroclitin J and kadsulignan E [55]. Activation via charge-transfer complex formation Under conditions where oxidative

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• ]. Similarly to the early transformations of thiepines, sulfur elimination was triggered by copper bronze at high temperature, thus leading to the conversion of the 6-membered cyclic disulfide into the corresponding thiophene. The 1,2-dithiin scaffold is found in natural products such as thiarubrines A and B

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• ; multi-step reactions; multicomponent reactions; one-pot synthesis; organocatalysis; tandem reactions; transition-metal-catalysis; The synthesis of pharmaceutical ingredients, natural products, agrochemicals, ligand systems, and building blocks for materials science has reached a high level of

• . Zhang, Ma, and W. Zhang reflects the state of the art in the α-amino acid-based [3 + 2] cycloaddition reactions of N–H-type azomethine ylides in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse bioactive heterocyclic compounds and natural products [9]. Computational studies

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• isostere of polar functional groups [5][6]. Chiral indoline is an important member of the class of nitrogen-containing heterocyclic compounds that often exhibits various pharmaceutical activities and exists in many natural products [7][8]. The enantioselective synthesis of chiral indolines has received

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• biologically active natural products such as BU-4664L. We are currently looking at this methodology to access some of these targets, including the agrochemical boscalid. Experimental Synthesis of o-(2-bromophenyl)aminoaniline (3a) Via Buchwald–Hartwig coupling: o-Phenylenediamine (1a, 0.05g, 1 equiv, 0.46 mmol

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• benzyl moiety on the substrate resulted in tandem Friedel–Crafts reactions to form the 1-aryltetraline products. These compounds share a close analogy to the cyclolignan natural products. Experimental observations and a DFT study support the involvement of an aldehyde intermediate during the Friedel

• reaction is possible upon elimination of the resulting benzylic alcohol on D, allowing another arylation forming E [18]. This complex sequence of transformations is herein applied to the synthesis of 1-aryltetralines, analogues of cyclolignan natural products having important medicinal applications [19][20

• -aryltetraline product 6 holds a skeleton similar to that of cyclolignan natural products (Figure 2), which have often been targeted by total synthesis [18]. Some of them like podophyllotoxin [25] and the semisynthetic derivative etoposide [26] have demonstrated valuable anticancer properties [19][20]. Thus, to

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• Over the past decades, the 8-aminoquinoline motif that could be found in several natural products [1] has attracted significant attention for its widespread usage in pharmaceuticals [2], agrochemicals [3], and functional materials [4]. In particular, the aminoquinoline scaffold has emerged as an

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• enables a rapid access to heterocycles containing a trifluoromethyl group. Keywords: cascade reaction; indole derivatives; photocatalysis; radical chain process; trifluoromethylation; Introduction Dihydropyrido[1,2-a]indolone (DHPI) skeletons are commonly found in natural products and pharmaceutical

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• fluorophors, previously shown to exhibit strong organic phosphorescence when mixed with specific additives [1][2][3][4][5]. Carbazole units are also found in drugs and natural products. They are also used in electrochemistry and as reagents in transamidation reactions [6][7][8][9][10][11][12]. The traditional

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• -dependent deamination pathway for the production of avenalumic acid or p-coumaric acid. Keywords: actinomycetes; avenalumic acid; biosynthesis; p-coumaric acid; polyketides; Introduction The genomes of microorganisms possess diverse biosynthetic gene clusters (BGCs) to produce natural products [1]. In

• particular, actinomycetes, a major source of bioactive compounds, have numerous BGCs in their genomes, but the majority of them are thought to be silent under laboratory conditions [2]. Because these orphan BGCs are often related to the production of unknown natural products, genome mining has been

• the ANS pathway, it has been shown that the ANS pathway is involved in the nitrogen–nitrogen (N–N) bond formation in the biosynthesis of several natural products [6][7][8]. Enzymes that catalyze N–N bond formation by using nitrous acid from the ANS pathway have also been characterized in several

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• motif, which is frequently found in natural products, bioactive molecules, and pharmaceuticals [1][2][3][4]. 1,2-Diazepine derivatives exhibit promising biological activities such as anticonvulsant, antibacterial, and antiproliferative effects [5][6][7][8][9][10][11][12][13]. Thus, the development of

• [22][23][24][25][26][27]. In addition, spirooxindole is also a privileged structural scaffold, which has been recognized as key structural unit in many bioactive natural products and pharmaceuticals with broad biological activities [28][29][30]. The development of elegant synthetic methodologies for

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• natural products of microbial origin such as HHQ and its C5-congener. Two compounds with high activity against S. aureus have been identified among the newly obtained quinolones, with MICs ≤ 3.12 and ≤ 6.25 µg/mL, respectively. Keywords: antibacterial; β-keto amides; enaminones; 4-quinolones; quorum

• operationally simple manner 2-alkyl-4-quinolones 8a–d, all of which are known from the literature [25][36][61][67][68] and two of them are natural products of microbial origin (8c [69] and 8d [70]). More importantly, the utility of the approach was demonstrated with the synthesis of the novel 2-alkyl-4

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• of mild reaction conditions allowed for the application of this method in the modification of complex natural products or pharmaceuticals. Moreover, this photoinduced decarboxylative approach demonstrated the potential for broader utilization in the construction of diverse C(sp3)–N and C(sp3)–X bonds

• readily accessible redox-active esters 3 and cost-effective NaI/PPh3 photoactivators under mild reaction conditions (Scheme 8) [14]. The methodology exhibited remarkable efficacy when applied to a wide range of natural products and pharmaceuticals, significantly expanding the synthetic utility of this

• active natural products. The direct functionalization of C–H bonds in enamides offers a convenient and versatile approach to access a wide range of functionalized enamides. In 2021, Fu and his colleagues successfully developed a novel method for the stereoselective alkylation of enamides 14 using iodine

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• activation [108][109][110]. Besides, pyrazolidine and pyrazoline compounds are highly valuable hereocycles which are found in many natural products and bioactive compounds. Among them, CF3-substituted pyrazolidines have already been shown to be highly bioactive [111][112][113]. Thus, Hu et al. chose

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• [1][2][3][4][5][6]. The great interest in PAMs is primarily due to their ability to bind various cations, anions, and neutral molecules [7][8][9][10][11][12][13][14]. In addition, some representatives of PAMs were found in various natural products and play an important role in living systems (e.g