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

• hydrodesulfurization of the daucanoid scaffold 109 (Scheme 20a) [108]. For the vinylcyclopropane desulfurizations (cf Scheme 18d) [112], this overreduction phenomenon was particularly troublesome, and reactions had to be very closely monitored, and stopped well before complete consumption of the starting material

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• ) triazolopyrazine scaffold (Series 4). The structures of all analogues were fully characterised by NMR, UV and MS data analysis; three triazolopyrazines were confirmed by X-ray crystal structure analysis. The inhibitory activity of all compounds against the growth of the malaria parasite Plasmodium falciparum (3D7

• . Antimalarial activity was significantly reduced when C-8 of the triazolopyrazine scaffold was substituted with CF3 and CF2H moieties, whereas incorporation of a CF2Me group at the same position completely abolished antiplasmodial effects. Keywords: antimalarial; characterisation; DiversinateTM; fluorine

• ; triazolopyrazine; scaffold; Open Source Malaria; Introduction Malaria is an infectious disease caused by Plasmodium parasites and is a major global threat to human health. The WHO World Malaria Report 2021, estimates 241 million cases of malaria and 627,000 deaths globally in 2020, an increase of 12% from the

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• structure as shown by the spherical bubble pores. Chitosan produces fragile matrices once they are dried. However, looking at the structures produced by the xanthan gum and locust bean gum matrices, the presence of a sphere-like porous scaffold is also evident when the material is not washed. Chemical

• simple hydrogel scaffold for the sorption of 1-naphthol. An aqueous sorbate mixture of five phenolic compounds has been also tested to assess the differences in the sorption behaviours of the different matrices. The absorbed amount changes as a function of the cyclodextrin/polysaccharide ratio, and the

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• terminal alkyne in 3an, and an alkyl chloride in 3ao proved compatible, associated with encouraging yields. In order to further demonstrate the utility of our protocol, a complex scaffold derived from lithocholic acid was tested, and was found to smoothly undergo the decarboxylative cyclization towards

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• review highlights recent total syntheses that incorporate the best of both worlds. Keywords: biomimetic synthesis; cascades; common scaffold; hydrogen atom transfer; photoredox catalysis; Introduction Societal needs push sciences into new directions, as the urge for new pharmaceutical leads grows, in

• their synthesis (Scheme 2). The synthetic variant of 3 was designed as the common scaffold 16, bearing the appropriate substitution for sequential revelation of carboxylic acid moieties. The highly congested decalin core of common scaffold 16 was obtained by a modified electrochemical polycyclization of

• of (−)-sclareol (43) [36] as the precursor to a photolabile Barton ester 59. When the latter was irradiated at 250 W in the presence of benzoquinone, a decarboxylated coupling occurred, yielding semiquinone 60, few steps away from the common scaffold 61. Following this protocol, researchers managed

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• ; Introduction The α’-methoxy-γ-pyrone motif is present in natural products and bioactive molecules [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Amidst these targets, a number contains a quaternary carbon vicinal to the scaffold, such as crispatene and photodeoxytridachione (Scheme 1a) [15]. These molecules

• chain to the 2,5-cyclohexadienone scaffold. Avoiding heat and light sensitive tetraenes, the convergent plan would also give the opportunity to assess an enantioselective synthesis of the targets, noting that the C14 epimeric product, isotridachiapyrone B, has also been isolated by Schmitz. Results and

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• and decoration of a NP scaffold. In comparison to biosynthetic assembly lines, intermediates are not permanently covalently bound to carrier proteins in discrete, multi-enzymatic assemblies. In both biosynthetic principles, the NP backbone is first assembled by core enzymes and then further modified

• by tailoring enzymes that decorate the NP scaffold. Assembly line-like pathways are characterized by mega enzymes, which can be subdivided into modules. Each module is responsible for the incorporation (and/or processing) of one building block into the nascent product. A “textbook” extension module

• , terpene cyclases generate the oftentimes multicyclic, hydrocarbon scaffold via a carbocation-mediated cascade reaction [30]. Terpene cyclases are obligatory components of canonical terpene pathways and are used to identify terpene BGCs (Figure 3B) [30][31]. RiPPs, on the other hand, lack genes that are

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

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

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

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 There are several reports of bioactive natural products that have a 3-hydroxy-2-methyllactone scaffold in the molecular structure. For example, cytospolide K2 [50] containing a 10-membered lactone and feigrisolide [51] containing a 7-membered lactone are known to exhibit cytotoxicity and

• . In addition, we demonstrated a new approach to a necic acid lactone 2j that is a diastereomer of monocrotalic acid, a key intermediate of monocrotalin. Bioactive natural products bearing a 3-hydroxy-2-methyllactone scaffold. Monocrotaline and its structural components. Molecular structure of necic

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

• molecular scaffold. Pondering various opportunities for post-condensational modifications of the 1,5-disubstituted 1,2,3-triazole core according to this strategy, we turned our attention to such powerful transformation as the azide–alkyne [3 + 2] cycloaddition (also known as the azide–alkyne click reaction

• reaction conditions were not further optimized (Scheme 1). The structure of tetracyclic product 5a was unequivocally confirmed by 1H and 13C NMR as well as single-crystal X-ray analysis. Compound 5a is representative of the hitherto undescribed bistriazole benzodiazepine scaffold. However, 5,6,7,8

• fragments in the structure of compound 5a) include compound 6 for the treatment of cognitive impairment [7], BET bromodomain inhibitors 7 [8] and 8 [9] for cancer treatment, σ1 receptor modulator 9 for diverse disorders [10] and bacterial regulatory RNA binder 10 [11] (scaffold A) as well as antidiuretic 11

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• -2,3-diones; spirooxindole; Introduction Compounds with a spirooxindole scaffold have attracted the attention of researchers, which is demonstrated by the publication of several reviews of both the biological activities of compounds with the spirooxindole moiety [1][2][3][4][5], and methods for

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

• = 44.4 and 14.29 µM, respectively). Although betulinic acid (1) exhibited greater antiviral activity than ursolic acid (2), the introduction of a nitroaryl-1,2,3-triazole substituent in 2 was more efficient than its introduction in scaffold 1. Moreover, all tested compounds showed low cytotoxicity in

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

• 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

• cross-coupling, and 2) immobilization on a solid support via reduction and reaction of the aniline with an electrophile such as polystyrene isocyanate. DOPO scaffold We previously reported the syntheses of both enantiomers of 8-phenyl DOPO 3 [38]. The syntheses proceed in only three steps (including the

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

• ]. In tripodal molecules, three functional arms are bound to a central trivalent scaffold, which can be a single atom (e.g., carbon, nitrogen, or phosphorus), a small ring (usually aromatic or saturated six-membered ring), or a macrocycle (Figure 1a). The functional properties of tripodal molecules are

• governed not only by the nature and length of the side arms but also by the size and geometry of the central scaffold [2][4]. By changing the scaffold, the volume of the cavity created by the three arms can be tuned allowing for the coordination of ions and molecules of different sizes [4]. For this reason

• , the central scaffold should also have a rigid geometry without much conformational flexibility to create a preorganized binding pocket. In this regard, the adamantane scaffold received some attention as it represents a conformationally strained analog of the cyclohexane ring [10][11][12][13]. However

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

• addition, a Lewis basic NEt2 (‒N(CH2CH3)2) group was introduced to the salen scaffold to facilitate purification, enhance catalytic efficiency, and improve the thermal stability, as was shown in the synthesis of fluorescent probes [41][42]. The chelating effect of salen compounds 1 with different metals

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

• approach to identify bioisosteres [70][71] or to undertake scaffold hoping [72] from an actual hit. On the other hand, concerning the virtual docking [73][74] of molecules on structurally characterized targets, past a rather sobering 2010 domesday report [75], a more recent review [76] is noteworthy at the

• ]. A survey of the evolution of commercially available chemical libraries is also of real interest [97]. It turns out that a low lipophilicity, a higher fraction of sp3 carbons [98] in the structures as well as a minimum of 20 compounds per scaffold are currently favored. A high sp3 proportion along

• vivo [171] as well as the rescaffolded analogue ND-11543 (32) [168][169]. In view of this, further scaffold-hopping was undertaken [172][173], as illustrated by the structure of the pyridopyrazole 33 which is also featuring the long aryl-bearing chain of telacebec (22) [174]. Concerning the structure

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

• that performs hydroxylation and epoxidation reactions of the β-amyrin (6) scaffold to produce 12,13β-epoxy-16β-hydroxy-β-amyrin [1][99]. Thus, CYP51H10 is an example of a neofunctionalised CYP recruited from primary sterol metabolism. Two members of the CYP87D subfamily decorate the tetracyclic

• scaffold in plants from the Cucurbitaceae family (Figure 3B). CYP87D18 (CYP85 clan) was identified as a multifunctional C11 oxidase involved in the biosynthetic pathway of mogrosides. Mogrosides, isolated from ripe fruits of Siraitia grosvenorii (Cucurbitaceae) are glycosylated triterpenoid saponins with

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• dihydrorosefuran, a compound allegedly identified in Artemisia pallens and Tagetes mendocina, has been developed. The key steps in the five-step 36% overall yield synthesis are a CpTiIIICl2 mediated Barbier-type allenylation of a linear aldehyde and the formation of a 2,5-dihydrofuran scaffold through a Ag(I

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• protease inhibitors. Given the potential usefulness of the benzothiazine scaffold as a biologically active unit and the peptidomimetic nature of many SARS-CoV-2 protease inhibitors [35], we decided to investigate the viability of attaching a 4H-benzo[b][1,4]thiazine-3-carboxylic core to amino acids

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

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

• biocatalytic dimerization reactions [20]. Contrary to flavone dimers and oligomers being abundant in nature, only limited dimeric compounds have been reported for isoflavones. Isoflavones bear a characteristic 3-phenylchroman skeleton, which is formed by the B-ring migration from the flavonoid scaffold

• , Supporting Information File 1) but not for 13–17, suggesting that CYP158C1 is also compatible with compounds with flavone scaffold. Apart from flavonoids, this enzyme also dimerized umbelliferone (18), a substrate of the fungal P450 KtnC [14][18], and RVT with relatively low efficiency (Figures S19 and S20

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

• , Russian Federation 10.3762/bjoc.18.109 Abstract A practically convenient and streamlined protocol for the trans-diastereoselective introduction of an aryl substituent at position 4 of the 1,4-dihydroisoquinol-3-one (1,4-DHIQ) scaffold is presented. The protocol involves direct Regitz diazo transfer onto

• 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

• summary, we have presented a practically convenient and streamlined protocol for the trans-diastereoselective introduction of an aryl substituent at position 4 of the 1,4-dihydroisoquinol-3-one (1,4-DHIQ) scaffold. The protocol relies on hitherto undescribed direct Regitz diazo transfer onto readily

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

• functional groups, which led to the discovery of actinopyridazinones with a unique dihydropyridazinone scaffold [11]. N2H4 generates similarly in the acid hydrolysate of azoxy compounds, and this feature has been exploited as proof for the presence of N–N bonds in the plant-derived methyl azoxy compound

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

• other compounds. To explore the biosynthesis of daturamycins in S. sp. KIB-H1544, especially the formation mechanism of the tricyclic 6/5/6 scaffold, the biosynthetic gene cluster of daturamycins was found and confirmed by gene knockout experiments. We also characterized the deduced peptide synthetase

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