Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• carbamate 8 in good yield [27][28][36]. In the next step, the aminohydroxylation was accomplished by potassium osmate(VI) as the catalyst and t-BuOCl in the presence of DIPEA affording oxazolidine-2-one 9 [27]. The reaction was found to be highly stereoselective, giving exclusively the diexo-fused tricyclic

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• duplex where the 2'-oxygen acts as an H-bond acceptor for water, potentially making a favorable contribution to the increased pairing affinity of LNA [161]. Constrained ethyl (cEt) nucleic acids (Figure 7H), which contain a [2.2.1] tricyclic core, have been developed and show improved potency when

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• synthesis of three types of highly functionalized azaheterocyclic scaffolds (dihydropyridazines, tetrahydropyridazines, and partially saturated tricyclic systems) from readily available hydroxypyrrolines and hydrazides are described. The directions of the transformation of a common initial intermediate

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• dipolar cycloaddition to produce tricyclic isoxazolidines [40]. The synthesis started from 5-hexyn-1-ol (4, Scheme 2). The alcohol was treated with dihydropyran followed by alkylation using butyllithium and then, acetal deprotection, providing the alcohol 5 as a key starting compound for the (±)-adaline

• % overall yields. A relevant consideration in Holmes’s synthesis is: the nitrone is the same common intermediate as Gössinger’s [25], which is cyclized to form the tricyclic adducts. While the Gössinger route started from the cyclic 1-hydroxypiperidine, Holmes performed in situ cyclization to prepare the

• tricyclic adduct (+)-23b, a precursor to (−)-adaline (1). This methodology, based on the synthesis of optically active β-sulfinyl nitrones, was proved to be efficient in the synthesis of (+)-euphococcinine (2) in 7 steps from piperidine (17), in an overall yield of 2.1%. Specific rotation for (+)-2 was [α

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tricyclic compound 25, which led to the synthesis of (±)-hirsutene (14) [22] (Scheme 1A). Refluxing azo compound 22 in acetonitrile generated the proposed biradical intermediate 23 through nitrogen extrusion. This intermediate underwent isomerization to 24 and intramolecular diyl trapping through a [3 + 2

• synthesis of (±)-hirsutene (14) used an alkylidene carbene as source of TMM diyl in the intramolecular [3 + 2] cycloaddition [24] (Scheme 1D). Heating of epoxyaziridinyl imine 32 produced tricyclic compound 36 in 57% yield as a single product. The authors proposed that heating of epoxyaziridinyl imine 32

• generates alkylidene carbene 33. Transformation of 33 to TMM diyl 35 enables an intramolecular [3 + 2] cycloaddition to give the desired tricyclic product 36. Trimethylenemethane (TMM) cycloaddition An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition was reported by Berson [28] and Little [14

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• tricyclic indoles bearing 3,4-fused seven-membered rings, 2‑arylpyridines, aminonaphthalenes and 3-phenylisoquinolines. In addition, this catalyst showed to be recyclable and could be reused several times without significant loss in activity during the course of the reaction process. Keywords: biomass

• activity in organic reactions. Tricyclic indole alkaloids bearing 3,4-fused seven-membered rings have attracted much attention because of their interesting molecular architectures and important biological activities [32][33]. Here the three-component reaction of 4-aminoindole (1a), 4-methylbenzaldehyde (2a

• were shown in Scheme 1. Aldehydes 2 with different functional groups on the benzene ring could react smoothly with compounds 1a and 3a, producing the corresponding 3,4-fused tricyclic indoles 4b–d with yields ranging from 46% to 64%. o-Anisaldehyde, with steric-hindrance effect, also reacted

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• -2,7-diyne reacted chemo- and stereoselectively in a Diels–Alder reaction with N-phenylmaleimide affording the tricyclic products as a mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to the

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• obtained with DeoxoFluor at elevated temperature (Scheme 2). A side-product in this fluorination reaction was the tricyclic compound 12, which presumably formed through an electrophilic aromatic substitution reaction of the activated alcohol intermediate. The inclusion of TMS-morpholine [29] reduced the

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• under halofluorination conditions. We expected that the imide moiety of this molecule would fix the carbonyl oxygen atom in a position remote to the C=C bond to avoid cyclization. Indeed, the bromofluorination of tricyclic 19 was successful. However, the process required repeated reagent addition and

• . Since the treatment of the reaction mixture at reflux conditions significantly increased the yield, the formation of 22 may follow a radical pathway. Using a modified literature protocol [35], the tricyclic imide 24 was also prepared and investigated. In halofluorination reactions, the behavior of 24

• was inferior. Interestingly, the same type of tricyclic compound (rac)-28 was formed from all four substrates (Scheme 18). The stereochemistry of the product was determined using NOESY measurements. Since the structures of the substances in the mixture of (rac)-8a,b are unknown, a possible mechanism

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• efficiently via a triplet-mediated pathway without use of any external sensitizer. Similar to bicyclic systems, some of the tricyclic system like 1h yielded 1,2-AS product 2h under similar reaction conditions [16]. Initially we envisaged two mechanistic pathways: the oxa-di-π-methane (ODPM) path

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• )8 followed by the addition of NMO), and starting from the pure anti diastereoisomer of 1,7-enyne 20, the expected bicyclic enone was obtained in good yield and high diastereoselectivity (de > 95%). An attempt to extend the PKR to the formation of a fused tricyclic structure, starting from 1,7-enyne

• 21, was unsuccessful and no tricyclic product was formed. Bonnet-Delpon and co-workers reported the one-pot synthesis of several CF3-containing N-tethered amines in good yields (54–86% over 2 steps) [49]. These products were subjected to metathesis reactions in the presence of Grubbs catalyst

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• the construction of the tricyclic scaffold of phenanthrenes and their nitrogen-containing analogues, mainly phenanthridines. The adoption (in most cases) of visible light to promote the processes makes the photocatalytic approach one of the mildest methods available for the construction of these

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• with the use of succinic anhydride. The results are evidence of an unexplored method for the access of the aforementioned tricyclic annelated systems incorporating a bridgehead nitrogen atom. The structures and relative configurations of the new compounds were established by means of 1D and 2D NMR

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• used similar disulfide-catalyzed [3 + 2] cycloaddition reactions for the synthesis of polycyclic frameworks. The irradiation of vinylcyclopropanes with alkenes or alkynes in the presence of dibutyl disulfide afford the desired bi- or tricyclic products with 54–88% yield (Scheme 2) [6]. In 2014, Maruoka

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• underwent a thermal rearrangement to generate tricyclic isobenzofurans 313 through the ring-cleavage of the thietanes. It was assumed that the rearrangement was assisted through participation of the oxygen lone-pair electrons [17] (Scheme 57). The silicon-containing phenyl triphenylsilyl thioketone (316

• Synthesis via intramolecular photochemical [2+2] cycloadditions: In 1985, Machida’s group reported the intramolecular photo-assisted [2 + 2] cycloadditions of N-allylthiosuccinimides 327 applying 1 kW high-pressure mercury lamp irradiation under a nitrogen atmosphere, giving the highly strained tricyclic

• thietanes 328 [91] (Scheme 62). One year later, the same group reported the intramolecular photo [2 + 2] cycloadditions of 2-allyl-N-methyldithiosuccinimide (329) with the same irradiation source at room temperature for 1 h, generating another highly strained tricyclic thietane 330. 2-((6,6-Dimethylbicyclo

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis as a key step, we herein survey representative examples where this reaction is effectively associated with traditional chemical transformations to produce bioactive synthetic targets. Review Artemisinin and nanolobatolide Due to its biological relevance, artemisinin, a tricyclic compound bearing a

• key step, adding this protocol to the existing synthetic or hemisynthetic procedures. Along this line, Oguri et al. elaborated an excellent strategy for assembling the tricyclic diene scaffold of artemisinin and its analogs that combines classical transformations with tandem dienyne ring-closing

• catalyzed by Grubbs 2nd generation Ru-carbene, these intermediates then led to the tricyclic sesquiterpenoid-like scaffolds I–VIII (Scheme 4), as suitable precursors for the synthesis of artemisinin and its analogs (1a–c). After selecting the optimal tricyclic intermediate, the installation of the bridged

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• and 6b: Figure 2 and Table S2 in Supporting Information File 1). The BODIPY cores of 3a and 6b are almost planar with smaller mean-plane deviations (defined by the 12 atoms of the tricyclic ring system) of 0.075 and 0.025 Å, respectively. The meso-mesityl groups are oriented perpendicularly to the

Absolute configurations of talaromycones A and B, α-diversonolic ester, and aspergillusone B from endophytic Talaromyces sp. ECN211

• Ken-ichi Nakashima,
• Junko Tomida,
• Takao Hirai,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 290–296, doi:10.3762/bjoc.16.28

• , indicative of a tricyclic ring system in the structure of 1. HMBC correlations (Figure 2) from H-2 to C-4 (δC 107.4) and C-9a (δC 108.0), from H-4 to C-2 (δC 112.7), C-4a (δC 155.9), and C-9a, and from H3-11 to C-2 (δC 112.7), C-3 (δC 148.2), and C-4 (δC 107.4) indicated the presence of a tetrasubstituted

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• that shows good overlap with drugs like levaquin, which is characterized by a complex tricyclic skeleton. The addition of a second aromatic ring, as the benzoyl or tosyl group of compounds 30–32, 34 and 35, increased the aromatic- and conjugation-related character of the structure, thus resulting in

• even more efficient in increasing the three-dimensional character of these compounds, as spiro tricyclic products were found to be more shifted towards the sphere-disc region of this chemical space, especially if compared to their corresponding starting materials (see Figure 4, compounds 5 and 26 with

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• cationic species. For instance, remodeling the hydrophobic pocket of the active site by single-point mutation, epi-isozizaene (33) synthase was engineered to produce various linear, monocyclic, bicyclic, and tricyclic terpene skeletons (Figure 9b) [119][120][121]. Another prominent example is cyclooctat-9

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• DBE and thus requiring 1 to be tricyclic. The 1H and 13C NMR data also revealed the presence of one hydroxylated quaternary carbon (C-9), two aliphatic quaternary carbons (C-4, C-10), two oxymethines (C-1, C-6), one aliphatic methine (C-5), one oxymethylene (C-12), two aliphatic methylenes (C-2, C-3

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• backbones. Thus, in the presence of presilphiperfolan-8-β-ol synthase (Bot2) a novel tricyclic product 70 was obtained from unnatural farnesyldiphosphate ether 69. The olfactory analysis revealed an ethereal, peppery and camphoric scent (Scheme 10) [39]. Future prospects of the fragrance industry will be

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• xanthone 6 [8]. A related strategy, adding lithium compound 7 to a preformed tricyclic system 8, was used by Nagano et al. to synthesize the Ge and Sn rhodamine analogues [14]. In a recent publication, Urano et al. synthesized the rhodamines 13–15 by coupling the triflate of xanthone 12 with boroxines 9b

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• deuterium labeling [33][34][35], to form the carbocation located at position C8 of dolabellatrienyl (B). By ring closure and formation of a novel C–C bond the tricyclic 5–8–5 ring system (C) is established. F107, F149, and the pyrophosphate moiety stabilize the carbocation at position C3 (Scheme 2 and