Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• Palau’amine (45), a dimeric pyrrole-imidazole-bisguanidine alkaloid, was first isolated from the marine sponge Stylotella aurantium in 1993 [16][17]. It received considerable attention from the synthetic community because of its broad range of biological activities and complex structure. In an early endeavour

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

• showed interesting antimicrobial and antibacterial activities [2][3][4]. (−)-Clausenamide was extracted and isolated from Clausena lansium which exhibited biological activities to enhance learning and memory capacities in amnesia animal models [5][6]. Doxapram, a non-natural compound, has been used to

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• is an abundant β-1,4-linked polysaccharide composed of N-acetylglucosamine as repeating unit (Figure 1) [1]. Biological activities of longer oligosaccharides, such as octasaccharide, have been paid much attention for many years. However, it is difficult to obtain pure oligosaccharides by isolation

• optimized conditions of the electrochemical polyglycosylation can afford oligosaccharides up to the hexasaccharide 6a. However, we were also interested in longer oligosaccharides, such as the heptasaccharide 7a and the octasaccharide 8a because of the biological activities [11]. Accordingly, the higher

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

• , 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

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• associated biological activities and relevance to the naturally occurring alkaloids [1], 1,4-dihydro-3(2H)-isoquinolones (1,4-DHIQs) undoubtedly represent a privileged scaffold [2] for drug design considering such diversely bioactive compounds documented in the literature as ligand for serotonin 5-HT1A

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

• , 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

• , fungi, plants, and marine sponges [1][2][3]. Azoxy natural products have occasionally been discovered by conventional isolation schemes guided by biological activities or physicochemical properties, which are not selective for the azoxy functionality. Consequently, there are only a few examples of azoxy

• 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

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

• structure β-carboline represents a promising class of pyridoindole alkaloids with a variety of biological activities which make them interesting synthetic targets [1][2][3][4][5][6][7][8]. Alkaloids containing the β-carboline nucleus in their molecular architecture are present ubiquitously in nature and a

• synthesis of various natural and synthetic products. MBH adducts itself display diverse biological activities like antifungal, antibacterial, herbicide, antiparasitic and antitumor as reviewed by Lima-Junior et al. (2012) [45]. It was envisaged that in comparison to the traditional methods like Pictet

• 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

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

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• analogues of γ-lactams, showing various biological activities, such as anti-inflammatory [15][16], antioxidant [17][18], and antitumor [18][19][20] (Figure 1). Various synthetic methods of 1,2-azaphospholidine 2-oxide and 1,2-azaphospholine 2-oxide derivatives have been developed to date. Two major

• important five-membered azaphosphaheterocycles, They are known as γ-phostams, including γ-phosphonolactams and γ-phosphinolactams. Benzo[1,2]azaphospholine 2-oxides are phosphorus analogues of indolinone derivatives and show important biological activities. Both γ-phosphonolactams and γ-phosphinolactams and

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

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

• endoperoxide containing alkaloids, terpenoids, and polyketides have been isolated from plants, animals, bacteria, fungi, and other organisms (Figure 1) [6][7]. Because of the high reactivity of the cyclic peroxide O–O bond, these compounds exhibit various biological activities [1][2][3][4][5]. For example

• ]. Artemisinin, the antimalarial agent isolated from the plant Artemisia annua [8][13][14], and ergosterol peroxides with anticancer and antiviral activities, identified in many fungi, algae, lichens, and plants, also belong to this group [15][16][17]. Due to the significant biological activities of the

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

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• heterocyclic scaffolds holding a broad range of biological activities [41][42][43]. For example, telmisartan, a 1,2-disubstituted benzimidazole derivative, is extensively used as an antihypertensive agent [44]. The substrate scope for the synthesis of variously substituted benzimidazoles is shown in Figure 2

• established from the X-ray crystallography data. Various methodologies are available in the literature toward constructing quinazolin-4(3H)-one derivatives [40][45][46]. Quinazolin-4(3H)-ones and its derivatives possess several biological activities such as antibacterial [47], antiviral [48], antitumor [49

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• biological activities such as anti-COVID-19 [5], anticancer [6][7][8], antibacterial activity against Staphylococcus aureus and Bacillus subtilis [9][10], antifungal agents against Candida albicans and phytopathogenic fungi [11][12], and antiproliferative against different cell lines (e.g., PC3, HCT-116, and

• enhanced the biological activities like anticancer [15][16], antibacterial [17], antimalarial [18], anti-inflammatory [19], and lead to a promising scaffold for the treatment of Alzheimer’s disease [20]. Our previous work showed that a combination between cholic acid and heterocyclic scaffolds improved the

• , and the product showed antiviral activity (Figure 1) [23]. In continuation of our ongoing research on designing compounds with potential biological activities, we herein report the design, synthesis, and antimicrobial assessment of novel cholyl 1,3,4-oxadiazole moieties (Figure 1). For developing new

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

• activities. The antineuroinflammatory activity of all isolates (1–9) was assessed by measuring nitric oxide (NO) production levels in LPS-stimulated murine microglia BV-2 cells (Table 4). Compounds 2 and 5–7 significantly reduced NO levels, with IC50 values of 52.21, 47.90, 61.61, and 25.35 μM, respectively

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• novel drugs could be the smoke of burning plants that contains more than 4000 chemical species [1] and among them numerous compounds possess biological activities in humans. The psychotropic effect of smoke is well known for centuries and its inhalation has different effects depending on plant material

• methodology for the preparation of analogues of karrikins with one sulfur atom in position C2 or position 6, or two sulfur atoms in both positions was improved; however, observed biological activities towards AChE were rather low. Structures of naturally occurring karrikins. Target compounds with highlighted

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• with four different substituents: in position 1 of the pyrazol cycle a 7-chloroquinolin-4-yl unit, in position 3 various amino or thio fragments, in position 4 a nitro and in position 5 a dichloromethyl group. Some biological activities of 7-chloroquinolinyl-substituted pyrazole derivatives have

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

• chlorides to form furoxans also known as 1,2,5-oxadiazole 2-oxides, a class of structures with important biological activities due to their unique electronic nature and coordination ability. Keywords: environmentally friendly; furoxans; 1,2,5-oxadiazole 2-oxides; trifluoromethyl-substituted isoxazoles

• and γ-amino alcohols [1]. Isoxazoles, appearing in 33 patents from the year 2016 to 2018 [3], are an important drug class due to their wide range of biological activities, such as anticancer [5], antibiotic [6][7], antimicrobial [8], antifungal [9], and anti-inflammatory [10]. Therefore, new methods

• donors have shown important biological activities due to their unique electronic and coordination ability [37][38], such as antitumor [39] and antiparasitic [40][41]. Previously, furoxans were synthesized via dimerization of hydroximoyl chlorides in the presence of a base, such as trimethylamine in ether

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

• shown a wide range of biological activities of menadione, such as anticancer [15][16][17][18][19][20][21][22], antibacterial [23][24][25][26], antifungal [27][28], antimalarial [29][30][31][32], antichagasic [33], and anthelmintic [34] effects. In these cases, the redox cycle of menadione, followed by

• ][41]. The quinone–hydroquinone and quinone–semiquinone interconversions, with ROS generation, are responsible for the wide range of biological activities of menadione and its derivatives. An excess of ROS in the intracellular environment can cause harmful effects on structures such as nucleic acids

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• commonly utilized as key intermediates for the synthesis of boron-containing peptidomimetics, which have been demonstrated to be efficient covalent ligands and valuable protease inhibitors endowed with various biological activities [5][6]. Going on with our interest in the synthesis of 3,3-disubstituted

• in 2014 [16]. Herein, we describe the unexpected results achieved by our work, that is the obtainment of unprecedented, bisoxindole-based, vicinal, tetrasubstituted diamines. Bisoxindoles represent a particularly intriguing class of compounds, because of their interesting biological activities and

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• biological activities, including anticancer [9], neuroprotective [10], antiproliferative and antifungal activities [11]. Due to the significant bioactive properties of the 3,4-dihydroquinazoline and 4H-3,1-benzothiazine moieties, many preparation procedures have appeared in the literature for the synthesis

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

• identification of a new bis-coumarin glucoside 1, together with three known bis- and tricoumarin glucosides 2–4, two flavonoid glycosides 5 and 6, and eleven lignan glucosides 7–17 (Figure 1). Herein, we present the isolation and structural elucidation of these natural products and their in vitro biological

• activities. Results and Discussion Compound 1 was obtained as a yellowish, amorphous powder. Its molecular formula was determined as C29H28O15 based on the HRESIMS sodium adduct ion observed at m/z 639.1319 ([M + Na]+, calcd for C29H28O15Na+, 639.1320), indicating sixteen degrees of unsaturation. Its UV

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

• , such as histone deacetylases. Keywords: chelated enolate; Claisen rearrangement; HDAC inhibitor; peptide; late stage modification; Introduction Among natural products, peptidic structures have entered the limelight due to their extraordinary biological activities [1]. Often found as secondary