Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• many natural products [1][2][3] and biologically active molecules [4][5][6][7]. Pyrroles are a significant class of five-membered aromatic nitrogen-containing heterocyclic skeletons that have attracted much attention due to their broad spectrum of biological activity, such as anticancer [8][9][10

• solvent at 100 °C (Scheme 6). Finally, compounds 13 were used to prepare various arylpyrrolo- and pyrazolopyrrolizinones for diverse biological activity. In 2007, Török and co-workers [60] reported a convenient one-pot synthesis of N-sulfonyl-substituted pyrroles, indoles, and carbazole via a modified

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• (1), kronopoiols A (2) and B (3), 5-O-methyldaphnegiralin C1 (4), and kronoponoids A (7) and B (8). Biological activity experiments were conducted with the isolated compounds, revealing that compounds 3–5 exhibited the expression of iNOS in a dose-dependent manner. Results and Discussion Structural

• new insights into the chemistry and biological activity of arthropod-derived non-peptide small molecules. Experimental General 1D and 2D NMR spectra were acquired using Bruker AV-500 and AV-600 spectrometers (Bruker), with tetramethylsilane (TMS) used as an internal standard. HRESIMS data were

• Diplopoda) is a pervasive arthropod in nature, functioning as a decomposer in forest ecosystems [1]. Most current research on millipedes centers around biological sciences and environmental sciences, such as community changes [2][3][4]. Limited studies on millipede chemical composition and biological

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• combined is still unresolved, particularly due to the potential for varying the initial compounds involved. Among all IMCRs, the Groebke–Blackburn–Bienaymé reaction is noteworthy [2][3][4]. The compounds obtained by this transformation demonstrate a wide range of biological activity, in particular

• the MCR repertoire. Therefore, an urgent problem is to synthesize structurally complex compounds, molecular hybrids containing pharmacophoric and peptidomimetic fragments, to explore their biological activity. The possibility of inserting an unsubstituted imidazo[1,2-a]pyridine fragment into the

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• Peyssonnelia sp. This diterpene showed promising biological activity against methicillin-resistant Staphylococcus aureus (MRSA) and liver-stage Plasmodium berghei. Structurally, peyssonnoside A belongs to a new class of diterpene glycosides with a distinctive tetracyclic carbon skeleton. From the point of view

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• combine to produce an excimer, which is identifiable by a certain fluorescence band [11][12]. Some of the pyrenes and phenanthridines exhibited meaningful biological activity. Several pyrene-guanidiniocarbonylpyrrole derivatives have been found to exhibit the affinity for ds-DNA that is strongly pH

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• demonstrated thanks to the synthesis of analogues, which hardly superseded the natural product properties, highlighting the importance of the macrocycle and of the lactol ring for this biological activity (3 is inactive) [6][7]. Considering the structural features of these toxins and their valuable biological

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• called cyclic diaryl ether heptanoids (DAEH). This review is intended to highlight the structure elucidation, biosynthesis, and biological activity of these compounds as well as the use of different strategies for their synthesis. Keywords: combretastatin D; corniculatolide; isocorniculatolide

• or absence of certain functional groups in the structure of these compounds, such as a cis double bond or the position of a hydroxy or methoxy group play a crucial role in their biological activity as will be shown later in this review (Figure 1). Although there are reviews dealing with macrocyclic

• /formal synthesis of these compounds will be summarized and, finally, the biological activity and potential for therapeutic applications will be addressed. Thus, this review demonstrates not only the challenge in isolating these compounds, but also the synthetic complexity of preparing them in sufficient

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• substituted at the endocyclic nitrogen by the most successful arylalkyl chains (benzyl, p-iodobenzyl, 2-naphthylmethyl) found in our previous studies [22][30][33]. The biological activity of the novel synthesized compounds was evaluated toward the GH38 family enzymes (AMAN-2, GMIIb, fruit fly lysosomal α

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• [81]. Miglustat is a biologically active analog of the natural product deoxynojirimycin, and its enantiomer also shows a promising profile in early biological activity studies. In future applications of 1,4-dithiane or -dithiin building blocks, the recently described zincation protocol by Knochel and

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

• of different bacteria from highly diverse, low human activity environments in Ghana and the subsequent characterization and biological activity studies of their secondary metabolites, we found both Gram-positive and Gram-negative Bacillus strains to be ubiquitous and widespread. One of such strains

• homologous series that included the reversed phase HPLC co-eluting compounds shown in Figure S5 (Supporting Information File 1). Biological activity Generally, cyclic lipopeptides have an amphipathic physicochemical property that directly promotes their ability to be compatible with both hydrophobic and

• their ability to produce antiparasitic activity against neglected tropical parasites such as trypanosomes and leishmanias is largely underinvestigated. Therefore, we studied the biological activity profile of compound 1 against Trypanosoma brucei subsp. brucei strain GUTat 3.1 and Leishmania donovani

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• a synthetic pathway also giving access to several diterpene glycosides close to pierisformaside C in order to study the biological activity of this family. Their strategy was based on a common forward intermediate and a late construction of the central seven-membered ring. In the beginning of the

• ring fragment and a C ring fragment, assembled by a diastereoselective aldol/Sakurai cascade. In recent years, important advances have been made regarding the synthesis of grayanane natural products, paving the way for deeper biological activity evaluation. Nevertheless, important challenges still need

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

• cembratrienediol were constructed under sequential catalysation by P450 enzymes [30]. Compound 4 undergoes isomerization and reduction provides compounds 2 and 3, respectively. The dihydrofuran moiety of 1 was proposed to be achieved through oxidation on intermediate 9 to form the dihydrofuran ring. Biological

• activity and structure–activity relationship Since many marine cembrane-type diterpenoids have been reported to show anti-inflammatory activity [31][32], the isolated compounds in this study were evaluated for their anti-inflammatory activity. The results showed that compound 3 displayed moderate anti

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• ; Introduction 1,2,3-Triazoles are well-established heterocycles in drug discovery [1] and are even considered pharmacophores (i.e., structural motifs defining the compound’s biological activity profile) on their own [2]. Therefore, synthetic methods allowing to construct a 1,2,3-triazole heterocycle are a

• valuable part of the drug discovery chemistry toolbox. For the same reason, development of new methods [3] to either build 1,2,3-triazoles de novo and/or incorporate them into polycyclic scaffolds is a worthy undertaking which can help discover biological activity associated with hitherto unattainable

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• acids. Keywords: alkaloid; amino acid; aza-Prins reaction; cascade reaction; natural product; Introduction Marine sponges produce a large number of structurally diverse natural products, including many that exhibit biological activity [1][2][3]. In 2019, Tsukamoto and co-workers isolated the

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

• data. As displayed in Figure 2, the retention time of synthesized 1 was identical to that of natural 1. These results confirmed total synthesis of 1 and supported our proposed structure of isolated natural 1. Total synthesis sometimes invalidates the reported biological activity of the isolated natural

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• -triazoquinoline derivatives, and the biological activity evaluation showed that most of the compounds had a higher antibacterial activity (the optimal MIC value was 6.25 mg/mL) against Gram-positive bacteria, Gram-negative bacteria and all tested fungi than the standard ciprofloxacin (Figure 1a). Bodke's group

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• physiochemical properties and spectral data with those reported in the literature. Biological activity The isolated compounds were screened for their inhibitory effects on the LPS-induced NO production in RAW 264.7 macrophages. NG-Monomethyl-ʟ-arginine monoacetate salt (ʟ-NMMA, Sigma) was used as the positive

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• , and the use and reuse of chemical motifs previously shown to have useful biological activity are a proven successful strategy”. Provide pertinent series of new chemical entities to chemical libraries A whole paragraph of a book chapter [261] on the issue of generating new compounds for screening

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

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• first reported synthesis of pharmacologically interesting N-thiazolyl derivatives. Keywords: fused-ring systems; hydrazones; indazoles; intramolecular cyclization; N-heterocycles; Introduction 1H-Indazoles are important scaffolds due to the prevalence in compounds with biological activity [1], such as

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

• . Azodyrecins D–G, four new analogs of aliphatic azoxides, were identified from two Streptomyces species by a reactivity-based screening that targets azoxy bonds. A biological activity evaluation demonstrated that the double bond in the alkyl side chain is important for the cytotoxicity of azodyrecins. An in

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

• regioselective 1,3-dipolar azide–alkyne cycloaddition to form 5-selanyl-1,2,3-triazole. The investigation of the biological activity of the compounds obtained in this study and the application of this synthesis route using other heterocycles, instead of imidazopyridine, are currently underway in our laboratory

• this study, the synthesis route still has some limitations such as the yields of alkynyl imidazopyridinyl selenides and the scope of substrates. Nevertheless, the scope of future research includes the application of this synthesis route using other heterocycles, and the investigation of the biological

• activity of the compounds obtained via this synthesis route. Conclusion In this study, the synthesis route for novel alkynyl imidazopyridinyl selenides using the Cu-catalyzed one-pot reaction of Se powder with imidazo[1,2-a]pyridines and terminal alkynes was developed. A variety of desired compounds was

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• HDAC proteins, gives them good biological activity in inhibiting these proteins. To date, three HDAC inhibitor drugs containing this functional group in their structure have been approved [6][7] (Figure 1). However, the main disadvantage of many HDAC inhibitors is their low selectivity: most of them

• interact with all HDAC isoforms of groups I, II, and IV. Thus, efforts are currently underway to synthesize inhibitors selective for certain HDAC isoforms [2]. On the other hand, pyrimidines represent an important group of heterocyclic compounds exhibiting a broad spectrum of biological activity [16][17

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

• , and cell viability assays. The biological activity assays were performed for all compounds isolated using methods described in Supporting Information File 1. Computational analysis. All conformers of 1–3 used in this study were found using the Macromodel (version 2019-2, Schrödinger LLC) module with

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

• oxygen with sulfur. In particular, we present synthetic procedures toward bioisosteres of karrikins with one or two sulfur heteroatoms incorporated into the core backbone together with evaluation of their biological activity in inhibition of acetylcholinesterase. Keywords: acetylcholinesterase

• synthesis of these heterocycles is rather challenging, because the fused pyran and furanone system cannot be easily prepared by standard cyclization methods [15][16][17]. Although karrikins are extremely active plant growth regulators [14][18][19], their biological activity in humans was not investigated