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

• were built using chiral amino acid building blocks and consequently have an intrinsic CD spectrum. While changes of poly rA–poly rU spectra upon titration with Phen-Py-1 and Phen-Py-2 were negligible (Figures S20 and S21, Supporting Information File 1), the addition of Phen-Py-1 and Phen-Py-2 to the ct

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• ]. Therefore, as relevant building blocks, tremendous efforts have been made to develop reliable methods for their synthesis. Transition-metal-catalyzed cyclopropanation of alkenes with trifluoromethyldiazoalkanes is a commonly used synthetic strategy for the construction of trifluoromethylcyclopropanes

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• provide the reader a nice overview. Since reviews dealing with transition-metal-catalyzed functionalization of compounds by C–H bond activation with fluorinated reagents [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] and vinylic, allylic or propargylic fluorinated building blocks

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• weak interactions with one of the triflates (I1–O3: 3.354 Å, I1–O5, 3.078 Å). We finally investigated the further reactivity of the synthesized azoiodazinium salts to elaborate their potential as synthetic building blocks (Scheme 1). Treatment of 5aa with Ac2O led to a non-selective ring opening at

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• iterative addition of geranyl (C10) or farnesyl (C15) building blocks derived from isoprene as starting unit and further structure rearrangement and functionalization [1]. This ubiquitous distribution highlights their pivotal role in living systems such as cell wall structural agent or ecological mediator

• articulated around a ring expansion of a fused cyclobutane/perhydroindanone fragment, leading to the cyclooctane motif. Interestingly, and unlike the previously reported strategies, the perhydroindanone precursor was prepared starting from achiral building blocks 157 and 158. They were engaged in a selective

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• Benedikt Kolb Daniela Silva dos Santos Sanja Krause Anna Zens Sabine Laschat Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany 10.3762/bjoc.19.17 Abstract Dienones are challenging building blocks in natural product synthesis due to their high

• enone building blocks 23 for the synthesis of clifednamides [54][62]. The addition of Schwartz's reagent proceeds as a syn-addition affording (E)-alkenylzirconocenes 24 from terminal alkynes [28]. Based on these precedents from the literature, we surmised that it might be possible to establish a related

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

• derivatives thereof at various oxidation states. The selected examples show how the specific heterocyclic reactivity can be harnessed for the controlled synthesis of carbon–carbon bonds. The reactivity is compared to and put into context with more common synthetic building blocks, such as 1,3-dithianes and

• (hetero)aromatic building blocks. 1,4-Dithianes have as yet not been investigated to the same extent as their well-known 1,3-dithiane counterparts, but they do offer attractive transformations that can find good use in the assembly of a wide array of complex molecular architectures, ranging from lipids

• 1,3-Dithianes are text book examples of versatile organic synthesis building blocks. They are familiar carbonyl protecting groups, but are more commonly known as ‘umpolung’ reagents, or acyl anion equivalents [1][2][3][4][5][6]. This is because they can be readily metalated and alkylated, allowing the

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• easily available, which have been established as versatile synthetic building blocks for the synthesis of cyclic scaffolds [25]. In 2016, Zhu et al. reported the first example of a Rh-catalyzed C–H functionalization of enaminones with alkynes and α-diazo-β-ketoesters to access naphthalenes [26]. Very

• , the reaction of the isocoumarin 3ia with p-toluenesulfonyl hydrazide proceeded smoothly to deliver hydrazone 5 in 66% yield (Scheme 4b, right). Of note, oxime and hydrazone compounds are versatile synthetic building blocks, which have been widely applied in transition-metal-catalyzed cross-coupling

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• on the success of the catalytic aza-Nazarov reaction. Keywords: α-methylene-γ-lactam; aza-Nazarov reaction; β-silicon effect; heterocycles; intramolecular cyclization; Introduction The rapid construction of aliphatic heterocycles from acyclic building blocks via cyclization or cycloaddition

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• also been investigated as useful building blocks for the synthesis of larger diaryl-based molecules, (hetero)aromatic tricyclic systems, or new aryl-moieties [24][25]. Most methods that generate DIS utilize iodoarenes as starting materials [26][27]. In these one-pot procedures, iodoarenes react with

• -established reagents for synthetic chemists. They are portrayed as an alternative to otherwise hazardous transition metals. This is due to their great reactivity in electrophilic group transfers [1][2][3][4], photo- or organocatalysis [5][6][7][8][9][10][11][12][13][14][15], and their utility as building

• blocks for the synthesis of natural products [16][17][18][19][20][21]. One subclass of HVIs is diaryliodonium salts (DIS), which have been used as versatile electrophilic arylation reagents in metal-catalyzed and metal-free reactions [22][23]. The corresponding cyclic diaryliodonium salts (CDIS) have

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• routes to chemical compounds of interest. With this technology maturing over the last decades, robust and oftentimes automated processes are now commonly exploited to generate fine chemical building blocks. The integration of effective inline analysis and purification tools is thereby frequently

• lower equipment cost will lead to an increasing number of users in academic and industrial laboratories where rapid delivery of high-quality samples of advanced structures is pivotal. At the same time, applications of these inline chromatography systems for the scaled synthesis of building blocks (>100

• -time IR and automated pump control to facilitate reagent addition and column robustness have been demonstrated in the synthesis of pyrazoles and other valuable building blocks [79]. In the same fashion as inline phase separations, the use of such cartridges is often considered to remove a reagent

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

• minimally harbors three core domains, responsible for the activation and loading, tethering, and condensation of building blocks and intermediates. The biosynthesis is directional and starts at the N-terminal module with the activation and loading of the first building block onto the assembly line (Figure

• large mega enzymes and generate NPs via the successive addition and/or modification of building blocks (e.g., non-ribosomal peptide biosynthesis) using conserved core domains. In discrete multi-enzymatic assemblies, distinct and mostly monofunctional enzymes catalyze the built-up of the NP scaffold and

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• building blocks 5 and 8 in hand, ketone 9 was prepared via a palladium-catalyzed Sonogashira coupling reaction in a yield of 95%. The precursor 10 for the gold(I)-catalyzed [19][20][21][22][23][24] cycloisomerization was then synthesized by treating ketone 9 with sodium bis(trimethylsilyl)amide (NaHMDS

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

• communication in the microbial world. Herein, we report the solid-phase total synthesis and structural confirmation of longicatenamide A. First, commercially unavailable building blocks were chemically synthesized with stereocontrol. Second, the peptide chain was elongated via Fmoc-based solid-phase peptide

• this study. Second, to realize the solid-phase synthesis, the C-terminus of the linear peptide was connected to 2-chlorotrityl resin [15] to give resin-bound peptide 5. Peptide 5 was divided into six building blocks 6–11 by retrosynthesis. At the beginning of the total synthesis, commercially

• unavailable building blocks 7 and 10 were chemically constructed from readily available starting materials. The synthesis of building block 10 commenced with the synthesis of compound 15 through Wittig reaction of Garner’s aldehyde (13) [16], which was readily obtained from tert-butyloxycarbonyl (Boc

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• and they are important building blocks in the synthesis as well as substructures of a number of biologically active natural and unnatural products [1][2][3][4][5][6][7][8]. Aziridines are valuable synthetic intermediates for the preparation of structurally complex molecules because of their

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• ) from an initial mechanical treatment of trichloroheptazine and Na3P, once again highlighting the importance of halogenated organic molecules as building blocks for graphitic heptazine materials (Scheme 4) [8]. Another halogenated molecule, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), proved to be

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

• Tripodal molecules are widely used as chelating ligands for transition metal catalysis [1][2][3], sensors for ions and small molecules [4][5], reagents for surface grafting [6], building blocks for the construction of supramolecular structures [7], polycyclic cage molecules [8], and porous materials [9

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

• enantioselective synthesis in modern chemistry turns out to be accumulatively essential for the preparation of chiral drugs, which is a huge growing market in the future. Indeed, the asymmetric ring opening of terminal epoxides is one of the most important strategies for synthesizing drug-like building blocks and

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

• patents just because of a lack of a simple synthetic method. Our contribution to alleviate this “blind spot” was an extensive exploration of the chemistry of alkoxypyrazoles (C) which provided synthetic building blocks useful to reach, amongst others, many new chemical entities with the general formula B

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• corresponding 1,2,3-cyclopropenium bromides was realized by a classical approach: combination of C1 and C2 building blocks, i.e., the addition of a carbene species to a triple bond of diarylacetylene, followed by treatment of the produced cyclopropene with HBr to convert it to the corresponding cyclopropenylium

• distilled at reduced pressure to give pure compounds. In a final step, we used the above mentioned approach of combining the C1 and C2 building blocks and found that chloroarylcarbenes, generated from the corresponding benzal chlorides 4b,c under the action of potassium tert-butoxide, reacted with 1,2-bis

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• building blocks. Experimental Procedure for the addition of n-BuLi to C3-silylated furfurals (preparation of compounds 3a–c and 4c) In a flame-dried round-bottom flask under argon was placed the appropriate C3-silylated furfural [15] and dissolved in freshly distilled THF (0.3 M). The solution was cooled

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

• Koert et al. in the racemic synthesis of the bisindole alkaloid (rac)-cladoniamide G (103, Scheme 17) [33]. The synthesis started with benzaldehyde 97 and indole 99 which were converted to the indole building blocks 98 and 100, respectively. These were connected to bisindole 101, which reacted with

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

• 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

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

• hydrogenation; Introduction Heterocyclic compounds with a benzothiazine moiety are attractive building blocks in medicinal chemistry. Benzo-1,4-thiazine derivatives possess a wide range of biological and pharmacological properties, such as anticancer and antitumor, antioxidant, antimicrobial, antibacterial

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

• from natural sources or by synthesis via chemical glycosylation [2]. Total syntheses of chitin and chitosan oligosaccharides based on conventional chemical glycosylation of protected monosaccharides as building blocks have already been reported. Convergent synthesis using oligosaccharide building

• oligosaccharides based on electrochemical preactivation of building blocks, is an alternative method for the synthesis of chitin oligosaccharides [3][4], it is also time-consuming and too sophisticated to prepare oligosaccharides composed of a single repeating structure. Thus, we assume that the electrochemical

• blocks can reduce the number of steps in the total synthesis. However, it requires manipulation of the anomeric leaving groups and deprotection of the protected hydroxy group at the 4-position prior to glycosylation. Although automated electrochemical assembly, which is a one-pot iterative synthesis of