Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• ]. Monocrotaline is used as compound for pulmonary hypertension model in rats. To date, some groups have reported synthetic methods and its synthetic supply will potentially contribute to hypertension treatment [54][55][56][57]. Although there have been a lot of reports of pyrrolizidine scaffolds or necine base

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• ]. Pyrrolothiazole and spirooxindole moieties occupy exclusive positions as valuable source of natural products and therapeutic agents in organic synthesis and drug discovery [60][61][62][63][64][65][66][67][68]. We have developed a number of asymmetric reactions to construct spirooxindole-based scaffolds through

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• of 2-unsubstituted imidazole 1-oxides with arylglyoxals and CH-acids [11]. This procedure is convenient for the synthesis of pharmacologically important compounds containing furopyranone and furocoumarin scaffolds. With this method, extensive varieties of polyfunctional imidazole 1-oxides can be

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• ) using click chemistry resulted in the synthesis of compounds 7 and 8 (Scheme 2). Biological assay The anti-RSV activities of triterpene derivatives, intermediates, and scaffolds were evaluated using MTT and SRB assays in A549 cells treated 4 hours after viral infection (Table 1 and Figure 2). Both

• of a 1-(3-nitrophenyl)-1,2,3-triazol-4-yl substituent in the C-28 position of both compounds 7 and 8 (EC50 = 0.314 and 0.053 µM, respectively) increased their antiviral activity, compared to that of the scaffolds 1 and 2 (EC50 = 5.3 and 17.3 µM, respectively) and acetylated compounds 3 and 4 (EC50

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzazoles containing oxazole and imidazole skeletons are the most commonly used scaffolds [1][2][3][4][5]. Therefore, it is crucial for the drug industry to develop methods for their syntheses [1][2][4][6]. For example, conventional benzoxazole synthesis methods involve the condensation of 2-aminophenol

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• asymmetric organocatalysis. In order to eliminate the need for C2-symmetry in common CPAs, various scaffolds containing C1-symmetrical thiophosphorus acids were chosen. These new compounds were synthesized and evaluated in the asymmetric transfer hydrogenation of 2-phenylquinoline. Although the efficacy of

• Prize in Chemistry awarded to McMillan and List. A subclass of organocatalysts introduced independently by Akiyama and Terada in 2004 [1][2], are the C2-symmetrical chiral phosphorus acids (CPAs) initially derived from the BINOL scaffold, and later extended to other scaffolds such as VAPOL [3] and

• enantioselective catalyst. On the other hand, their successful completions attest to the inexpensive and scalable requirements we had set. Indole scaffolds The synthesis of racemic tryptophol CPA 1 is shown in Scheme 2. Commercially available tryptophol (5, 225 $/mol) was N-arylated into 6 via copper-catalyzed

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• molecule is fixed by a system of H-bonds in a pocket created by amide units and the triazinane ring. This creates opportunities for a rational design of supramolecular receptors for alcohols based on 3N-TAAD as a template. Adamantane-based tripodal scaffolds and current work. General view of the 1,4,6,10

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• ]. Jones et al. designed a cyclooctene-based Co–salen macrocycle catalyst for the phenolic KR of epichlorohydrin and 1,2-epoxyhexane [21]. However, these Co–salen systems suffer from several limitations such as tedious preparation of salen scaffolds, excess use of epoxides, high catalyst loadings, narrow

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• to efficiently bind to oxo-anions such as carboxylates [10]. These compounds were already used to specifically address carboxylates on the surface of proteins. Many artificial receptors based on guanidinium scaffolds use hydrogen bonding, charge pairing, and hydrophobic interactions to complex oxo

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• sterol scaffolds have drastically different three-dimensional shapes. For this reason, CYPs are typically specific to a certain group of triterpenoid scaffolds. Hence, we summarised our list of 149 triterpenoid/steroid CYPs (Table 1) according to their target scaffold. Figure 3 covers plant CYPs acting

• on steroid, cucurbitacin, or simple tetracyclic triterpenoid scaffolds. Important scaffolds here are campesterol (1), β-sitosterol (2), cholesterol (3), cucurbitadienol (4), and dammarenediol-II (5). Not surprisingly, CYPs involved in the biosynthesis of essential sterols in plants are highly

• -dihydroxycucurbitadienol to form trihydroxylated mogrol in yeast [102]. CYPs acting on pentacyclic 6-6-6-6-6 triterpenes, which include the extremely important and widespread scaffolds β-amyrin (6), α-amyrin (7), and friedelin (8), are summarised in Figure 4. Of particular relevance in this area is the CYP716 family

Enzymes in biosynthesis

• Jeroen S. Dickschat

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

• 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

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

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• sacrificial anode would be a promising approach toward synthetically valuable vic-1,2-diol scaffolds without using low-valent metal reductants. However, sacrificial anodes produce an equimolar amount of metal waste, which may be a major issue in terms of sustainable chemistry. Herein, we report a sacrificial

• electrolysis; Introduction Carbon–carbon bond formation is one of the most fundamental and important reactions in synthetic organic chemistry. Reductive coupling of carbonyl compounds known as pinacol coupling would be a powerful method to construct vic-1,2-diol scaffolds through C–C bond formation [1][2

• ]. Such scaffolds are widely utilized as versatile building blocks in the synthesis of biologically active compounds [3][4][5][6][7], chiral auxiliaries [8][9], and chiral ligands [10][11][12][13]. Traditional pinacol coupling reactions are performed with a stoichiometric or even excess amount of low

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

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

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• acetonitrile at room temperature gave the unexpected products 4a–k in moderate to good yields in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as base promoter and the results are summarized in Table 3. It can be seen that the products 4a–k contain two scaffolds of each phenacylmalononitrile and

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

• -kaurane skeletons outlined here may provide an attractive route to prepare other privileged diterpene scaffolds. Keywords: artificial pathway; ent-kaurene; Escherichia coli; overproduction; terpentetriene; Introduction Diterpenoids, of which there are over 34,000 members (http://terokit.qmclab.com

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

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

• 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

• of this library will be reported in due course. Biologically active cholic acid hybridized with different heterocyclic scaffolds. Structures of target compounds 4a–v. Synthesis of cholyl 1,3,4-oxadiazole-2-thiol 2. Synthesis of cholyl 2-(propargylthio)-1,3,4-oxadiazole 3. Synthesis of target

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

• unknown, that could have untapped potential in medicine. The study of the relationship between the components of plant-derived smoke and MAO and/or AChE can lead to safe and efficient drugs and drug scaffolds from a yet unexploited resource. One very important bioactive constituent of smoke of burning

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• Mannich reactions; supramolecular catalysis; thiourea; Introduction In the past decades, the development of supramolecular chemistry has enabled abundant host scaffolds and assembly tools for boosting catalytic processes, and stimulated the emergence of supramolecular catalysis [1][2][3][4][5][6][7][8][9

• ][10][11][12][13][14]. Among which, macrocyclic compounds have attracted extensive attentions due to their enzyme-mimicking cavity and preorganized binding sites [4][6][15][16]. Various macrocyclic compounds including the privileged scaffolds like cyclodextrins [17][18][19], calixarenes [20][21][22][23

• % yields. It is worth noting that common dilute conditions for macrocyclization reactions was not required here. Due to the very high efficiency, gram-scale preparation of the chiral macrocycles was readily achieved (see Supporting Information File 1). To enrich the diversity of the macrocyclic scaffolds

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

• and operational simplicity through one pot reaction. Keywords: chemoselective conjugate reduction; dispirocyclopentanebisoxindole scaffolds; metal-free; one-pot operation; reductive cyclization; Introduction There is a vast demand of the structurally complex spirooxindole scaffold which is an

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

• reaction, among pericyclic reactions, is a very important synthetic approach to obtain several molecular scaffolds, including naturally occurring molecules, drugs, polymers, and heterocycles with promising biological activity. Especially, Diels–Alder reactions involving quinones and dienes as starting

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• versatile starting materials in organic synthesis [1][2]. Specifically, due to their keto–enol tautomerism and high reactivity, diketones are excellent precursors for different pharmaceuticals [3]. Cyclic 1,3-diketones have been widely exploited to access enantiomerically enriched scaffolds with increased

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• scaffolds with versatile medicinal properties, including anti-Alzheimer, anti-inflammatory, anticancer, antidiabetic, and antileishmanial activity [1]. Since the first synthesis of paullones (scaffold A in Figure 1) in 1992 [2], and disclosure of their Cdk inhibiting potential, several other analogues were

• unit is shifted and the indole ring is flipped (D). Isomer D has been shown to be a potent tubulin-polymerase inhibitor, while B was only mildly cytotoxic towards cancer cells at a concentration of 1 µM [5][6]. Backbone C, despite being very similar to the other three scaffolds, remained a synthetic

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• , we synthesized a Ni–chitosan complex and exploited the coordination properties of the complex to use it as an effective and recyclable catalyst towards the green synthesis of C5–C6-unsubstituted 1,4-dihydropyridine (1,4-DHP) scaffolds. Ultrasonic irradiation is an important technique in the toolbox

• (NPs) and therefore automatically increases the dispersibility of the catalyst throughout the medium, resulting in a higher catalytic activity [23]. 1,4-DHPs are considered one of the most useful molecular scaffolds in medicinal chemistry. The scaffold is the main constituent of several crucial drugs

• unsubstituted double bond next to the nitrogen atom permits a DHP to react as an enamine, for further transformation to complex heterocyclic scaffolds [26]. The exposed double bond can also undergo modification to produce different kinds of moieties. There are only few reports on the synthesis of C5–C6

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• , sulfonyl chlorides are good building blocks to intermediates and complex scaffolds of sulfonamides. Gordon, Maskill, and Ruasse [1] have reviewed “Sulfonyl Transfer Reactions” in a broader sense than the coverage of the present contributions. In particular, an appreciable amount of the coverage in the