From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• amines plays a crucial role in organic synthesis [1][2][3][4][5][6]. In one respect, it is relevant to protect the amine group straightforwardly and under mild conditions [7][8]. On the other hand, the formamide and acetamide moieties are found in many active pharmaceutical ingredients (APIs) and natural

• products [1][9]. N-Formyl derivatives were used as building blocks in Vilsmeier–Haack reactions [10][11] and for preparing molecule drug substances, various heterocycles, formamidines, isocyanates, and isocyanides [12][13][14][15][16][17]. The large number of procedures reported in the literature witnesses

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• structure is an important scaffold which can be found in many pharmaceutical active natural products and synthetic medicinal compounds [2]. Pramanicin, for example, is a 2-pyrrolidone-containing natural product isolated from a lactose-containg liquid fermentation of a sterile fungus growing in grass which

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• remarkable transformations in nature. Some of the most interesting transformations catalyzed by enzymes are known from the biosynthetic pathways towards natural products. For instance, class I terpene synthases can convert highly complex transformations of an acyclic precursor, such as farnesyl or

• the molecular scaffolds of natural products [5]. During the past two decades, large amounts of genome information from thousands of organisms have become available. This allows scientists today to gain direct access to the encoded catalysts through expression in easy-to-handle heterologous hosts, such

• different aspects of studying the roles of enzymes in the biosynthesis of natural products. Also contributions showing the application of enzymes in synthetic organic chemistry will be welcome. I am grateful to all colleagues who have contributed to this issue and to the Editorial Team of the Beilstein

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• recognized as important molecules. For example, cyclopropane derivatives are found in both natural products and pharmaceutical products. The cyclopropane skeleton is also found in agrochemicals, especially pyrethroid, as an insecticide, is one important compound. Cyclopropanes also play a significant role in

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• , Zhejiang Province, China Institute of Natural Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China 10.3762/bjoc.18.113 Abstract Dimerization is a widespread natural strategy that enables rapid structural diversification of natural products

• . However, our understanding of the dimerization enzymes involved in this biotransformation is still limited compared to the numerous reported dimeric natural products. Here, we report the characterization of three new isoflavone dimers from Streptomyces cattleya cultured on an isoflavone-containing agar

• , and plants, have the ability to produce homo- or heterodimeric natural products, which enables rapid structural diversification from simple monomers [1]. Often, the dimerized products exhibit significant biological activities due to the increased functional group density or complex stereochemistry, as

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• -determining step. This work can contribute significantly expanding the applications of N-substituted carbonylimidazoles. Keywords: amines; carboxylic acids; isocyanates; monomethylamines; N-substituted carbonylimidazoles; reduction; Introduction N-Methylamines are widely found in natural products, fine

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

• Generation Natural Products Chemistry, Tokyo 135-0064, Japan National Institute of Advanced Industrial Science and Technology (AIST), Tokyo 135-0064, Japan Japan Biological Informatics Consortium (JBIC), Tokyo 135-0064, Japan Okinawa Institute of Science and Technology Graduate University, Okinawa, 904-0495

• , Japan Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 060-0812, Japan 10.3762/bjoc.18.102 Abstract Only a few azoxy natural products have been identified despite their intriguing biological activities

• vitro assay elucidated the tailoring step of azodyrecin biosynthesis, which is mediated by the S-adenosylmethionine (SAM)-dependent methyltransferase Ady1. This study paves the way for the targeted isolation of aliphatic azoxy natural products through a genome-mining approach and further investigations

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• daturamycins was identified through gene knockout and biochemical characterization experiments and the biosynthetic pathway of daturamycins was proposed. Keywords: biosynthesis; diarylcyclopentenone; polyporic acid synthetase; p-terphenyl; Streptomyces; Introduction Natural products containing a terphenyl

• rare class of a tricyclic 6/5/6 system, could also belong to p-terphenyl derivatives from a biosynthetic perspective. To date, more than 230 natural products containing p-terphenyl have been unearthed in nature, among them many p-terphenyls were isolated from fungi, only a few were discovered from

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• halides are valuable compounds with potent bioactivities [1][2][3][4][5] (Figure 1) and are utilized as crucial precursors for various metal-catalyzed cross-coupling reactions [6][7][8][9]. They are frequently used as synthetic intermediates in several value-added syntheses of natural products

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• Translational Neuroscience – DANDRITE, Universitetsbyen 81, 8000 Aarhus C, Denmark 10.3762/bjoc.18.97 Abstract Terpene synthases are responsible for the biosynthesis of terpenes, the largest family of natural products. Hydropyrene synthase generates hydropyrene and hydropyrenol as its main products along with

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• large number of natural products are reported representing this scaffold [9][10][11][12][13][14][15][16]. The key precursor used in the biosynthesis of β-carboline is ʟ-tryptophan which forms the basis of great abundance of β-carboline-containing natural products [17]. A broad spectrum of biological

• of β-carboline-containing compounds [27][28][29][30]. Figure 1 summarizes some examples of β-carboline-based drugs and bioactive natural products some of which have even been commercialized successfully showing the importance of this nucleus [31][32][33]. This pharmacological richness and colossal

• products 8 (Morita–Baylis–Hilman + Michael adducts). Antimicrobial evaluation of the title compounds is underway and will be reported in due course. Few examples of β-carboline-based drugs and bioactive natural products. 1/3-Formyl-9H-β-carboline: new synthons for the synthesis of β-carboline-fused and

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

• Pharmaceutical Science, Nanchang University, Nanchang 330006, China Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China Open Studio for Druggability Research of Marine Natural Products, Pilot National Laboratory for Marine Science

• 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

• configuration determination of natural products with stereogenic centers near the chromophore groups [20], was applied, since there is an α,β-unsaturated ketone chromophore nearby C-5 and C-2 in compound (+)-1. Thus, the theoretical ECD spectrum of (+)-1 was calculated by the DFT calculation method at the b3lyp

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• categories of diterpenoid natural products with complicated polycyclic carbon skeletons and significant pharmacological activities. Despite exciting advances in organic chemistry, access to these skeletons is still highly challenging. Using synthetic biology to engineer microbes provides an innovative

• complexity [12]. Additionally, chemical transformations from commercial natural products are also tedious and currently limited to a few diterpene skeletons [8]. Engineering microbes via synthetic biology provides new opportunities to produce terpenoid carbon skeletons. All terpenoids are derived from the

• diterpenoids are two categories of diterpenoids that are widely distributed in terrestrial plants, fungi, and a few bacteria and possess broad pharmacological bioactivities [1][2][3]. Representative natural products containing these skeletons are terpentecin (cytotoxic and antibiotic), salvinorin A (kappa

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• mill; borylation; cross-coupling; mechanochemistry; solid-state reaction; Introduction Arylboronic acid and its derivatives are indispensable reagents in modern synthetic chemistry because they have been frequently used for the preparation of many bioactive molecules, natural products, and functional

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• substances. Many biologically active natural products have a spirocyclic skeleton in their structure [1][2]. In this regard, there is interest in studying heterocyclic spiro compounds for drug discovery. These compounds were found to exhibit a broad range of biological activities, including antioxidant [3

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• -triaryl-substituted and 1,2,5,6-tetrasubstituted nicotinates. Keywords: isoxazole; methyl nicotinate; molybdenum hexacarbonyl; 4-pyridone; ring expansion; Introduction Pyridine moieties are present in many natural products, drugs, pesticides and industrial materials. Pyridine fragments are used in drugs

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

• 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

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

• attention in the field of natural products and organic synthesis. In this review, we summarize the structural analyses, mechanistic investigations, and proposed reaction mechanisms of endoperoxide-forming oxygenases, including cyclooxygenase, fumitremorgin B endoperoxidase (FtmOx1), and the asnovolin A

• endoperoxygenase NvfI. Keywords: biosynthesis; endoperoxide; enzyme; natural products; X-ray crystallography; Introduction Endoperoxide-containing compounds form a large group of natural products with cyclic peroxide structures [1][2][3][4][5]. These compounds are widely distributed in nature, and many

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• ; tri(n-butyl)phosphine; Introduction Spirooxindole is a privileged heterocyclic core existing in many natural products and medicinally relevant compounds. A variety of spirooxindole derivatives has been identified with a broad range of biological activities [1][2][3][4][5]. On the other hand

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• important structural motif that is embodied in a number of bioactive natural products and medicinally relevant compounds [1][2]. Among various spirooxindole motifs, bispirooxindoles fusing two spirooxindole cores exhibit a wide range of important biological activities, for example, anticancer

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• Md Imran Hossain Md Imdadul H. Khan Seong Jong Kim Hoang V. Le Department of BioMolecular Sciences and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Mississippi 38677, USA Natural Products Utilization Research Unit, United States Department of

• hours, which provides an environmentally friendly access to 3,4,5-trisubstituted isoxazoles, an important class of structures found in numerous bioactive natural products and pharmaceuticals. Additionally, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a

• ; 3,4,5-trisubstituted isoxazoles; Introduction Isoxazoles are a privileged class of five-membered heterocycles, which are found in numerous bioactive natural products [1][2] and synthetic small molecule drugs [3][4], and are used as important precursors for the synthesis of β-hydroxycarbonyl compounds

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• building blocks for the production of other important molecules (e.g., amino alcohols, diols, etc.) [40][41][42][43][44][45][46] and potential pharmaceuticals. α-Hydroxyketones are structural subunits of natural products [47][48][49] and compounds possessing immunosuppressant [50], antidepressant [51

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

• materials allow for the synthesis of more complex molecules such as natural products. Within this scope, the menadione (10) molecule has been explored as substrate for this versatile reaction. Ryu and co-workers described an enantioselective and structurally selective Diels–Alder reaction for the synthesis

• -LED light [111]. Under these conditions, menadione (10) and terminal alkynes 66 underwent a [2 + 2] cycloaddition reaction generating compounds containing cyclobutene rings (67a–c), that are important precursors in natural products syntheses. It is important to note that the choice of the blue-LED

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

• containing side chains with 23,24-dimethyl groups and (17)20E double bond, have been reported to be frequently isolated from soft corals of this genus, some of them exhibited anti-inflammatory [4], cytotoxic [5][6], and antibacterial activities [7]. To search for bioactive natural products, we have

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

• measured and compared with literature values of known natural products. The optical rotation of compound 5 was consistent with the reported value for amamistatin B ( = −9.8) [7]. Similar optical rotations were determined for 1, 3, and 4 ( = −1.4, −11.8, and −11.5, respectively). Furthermore, these

• iron affinity. On the basis of biosynthetic precedence [14], a plausible pathway for the natural products isolated in this study can be postulated (Figure 4). According to this proposal, compounds 1–4 are intermediates in the formation of 5, which has the strongest iron affinity and likely represents

• -type siderophores. Structurally, compounds 1–5 are closely related to formobactin [10], brasilibactin [23], nocardimicin [24], and terpenibactins [15]. While the core scaffold of these natural products is conserved, they differ in the length of their fatty acid residues, their methylation pattern, and