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

• , a composition of coumarin, oak moss, geranium and bergamot, commercially launched by Houbigant [4]. The major constituents of geranium oil include myrcene (1), menthone (2), α-pinene (3), geraniol (4a), geranyl acetate (4b), geranyl butyrate (4c), citronellol (5), limonene (6) and linalool (9a). As

• introduced until the dawn of 19th century and first and foremost coumarin played a key role, first synthesised by Perkin in 1868 [7][8]. Following this breakthrough, many other perfumes were created based on synthetic molecules born from the newly established discipline synthetic organic chemistry. This made

Ultrafast processes triggered by one- and two-photon excitation of a photochromic and luminescent hydrazone

• Alessandro Iagatti,
• Baihao Shao,
• Alberto Credi,
• Barbara Ventura,
• Ivan Aprahamian and
• Mariangela Di Donato

Beilstein J. Org. Chem. 2019, 15, 2438–2446, doi:10.3762/bjoc.15.236

• coumarin 153 (δ1 = 47.4 GM [34]) as a reference, for which transient absorption spectra have been measured upon excitation at both 400 nm and 785 nm (see Figure S4, Supporting Information File 1), the estimated value for 1 in toluene is 12.6 GM, a value in good agreement with that previously determined

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• coumarin derivative 1y (BCVP), provides a bimodal (colorimetric and fluorimetric) output towards G4-DNA through the selective disruption of H-aggregates formed in buffered solution [59]. In the meantime, numerous other styryl derivatives were reported as efficient “light-up” probes for G4-DNA and RNA

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• , mechanosynthesis of lipids by ball milling techniques has remained essentially unexplored. In this work, a multistep synthetic route to access mono- and diacylglycerol derivatives by mechanochemistry has been realized, including the synthesis of diacylglycerol-coumarin conjugates. Keywords: ball mill; coumarin

• ) was separated from the unreacted starting materials, and analyzed by UV–vis spectroscopy (Figure 3). Comparison of the UV–vis spectra of 6a and 10a/10a’ showed the successful conjugation of the DAG with the coumarin moiety [47]. Conclusion The implementation of ball milling techniques has provided the

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• new structure. This concept has recently received attention by the pharmaceutical industry because it provides new options to develop more specific drugs for the treatment of persistent and challenging pathologies [27][28] (Scheme 1). The indole, coumarin, quinoline, chromone and fluorene moieties are

• . [52] and by Mousavizadeh et al. [53] through the three-component reactions of indole and coumarin, but in all cases, ordinary aliphatic and aromatic aldehydes as the third partner, mediated by a catalyst or by a biphasic system as solvent, respectively, were used. The lack of structural diversity in

• the indole and coumarin partners also characterizes these approaches, Scheme 2. Continuing our current program on the synthesis of quinoline-based heterocyclic compounds of biological interest [54][55][56][57], we describe here a Yonemitsu-based direct and reproducible three-component synthesis of

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• to antineurodegenerative activities [2][3]. The majority of natural coumarins are secondary metabolites isolated from plants [5][6][7]. A commonly used taxonomy for these natural products (which has been extended to the non-natural analogues) is based on the coumarin structure (Figure 1) [4][8]. It

• which a heterocycle is annellated to the benzene ring of the coumarin skeleton. In particular the latter group is often further divided into sections according to ring size (five-membered rings: furanocoumarins; six-membered rings: pyranocoumarins) and location of the annellated ring (linear vs angular

• the coumarin skeleton. For the latter group of syntheses several classical methods, such as the Perkin condensation, are available, which have been covered in earlier reviews [5][6][8]. Unfavorable reaction conditions, low yields and a sometimes limited scope make the development of alternatives to

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• -acenaphthenequinone derivatives, tetrahydrobenzo[a]xanthenone derivatives, tetrahydrobenzo[a]acridinone derivatives, 1-amidoalkyl-2-naphthol derivatives, 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)trione derivatives, quinoline derivatives, bis-coumarin derivatives, 2H-indazolo[2,1-b]phthalazinetrione derivatives

• supported 1,4-diazabicyclo[2.2.2]octane 70 was reacted with ClSO3H in cold chloroform to give new -SO3H functionalized SiO2. The authors studied its catalytic behavior in the synthesis of bis-coumarin derivatives 72 using a solvent-free reaction of aryl aldehydes containing electron-donating and electron

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme. Keywords: acetylcholinesterase inhibitor; 3-aminocoumarin; N-benzylpyridinium; dual binding site

• . Hybrid compounds such as huperzine A–tacrine hybrids [5], donepezil–tacrine hybrid related derivatives [6][7] and tacrine–indole hybrids [8] with dual-binding site properties exhibit potent AChE inhibition activities. In addition, coumarin compounds linked with various side chain moieties [9][10][11] as

• well as with benzylpyridinium moieties [12][13][14] have been reported as dual-binding site AChE inhibitors. Recently we have reported the AChE inhibitory activity of the coumarin derivative, scopoletin conjugated with a pyridinium side chain (Figure 1) [15] and a docking study revealed that the

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• cyclization with the aid of HCl followed by pyridinium dichromate (PDC) oxidation (Scheme 8). Schmidt and co-workers [39] described an efficient route involving RCM and SM coupling towards the synthesis of 8-aryl-substituted coumarin 64, a natural product isolated from the plant Galipea panamensis. To this

• protocol. Synthesis to 8-aryl substituted coumarin 64 via RCM and SM sequence. Synthesis of cyclic sulfoximine 70 via SM and RCM as key steps. Synthesis of 1-benzazepine derivative 75 via SM and RCM as key steps. Synthesis of naphthoxepine derivative 79 via RCM followed by SM coupling. Sequential CM and SM

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• discovered the one-pot synthesis of coumarin derivatives via hydrocarboxylation/alkene isomerization/cyclization reactions (Scheme 22) [49]. A key of the sequential reactions is a use of aromatic alkynes bearing a momo-protected hydroxy group at the ortho position on the aromatic ring (23). The corresponding

• coumarin derivatives were obtained in moderate-to-good yields. Notably, ketone (24e), ester (24d) moieties were tolerated in the reaction. In addition, 2-quinolones (24f and 24g) were obtained using alkynes bearing a Boc protected carbamate in place of the MOM protected ether. Scheme 23 shows a plausible

• coumarin derivative. Rhodium catalysts Carboxylation of aryl and alkenylboronic esters Aryl and alkenylboronic acids or their esters are of interest in organic synthesis because they are commonly used for C–C bond-forming reactions such as Pd-catalyzed Suzuki–Miyaura coupling reactions [50][51][52][53

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• Michael addition pathway (see Figure 1b) [6]. Prompted by the interest of developing novel light-driven microfluidic methods for the construction of biologically relevant molecular scaffolds, we investigated the reaction between MBP 1 and 3-unsubstituted coumarin (2a) and chromone (3a, Figure 1c). It was

• enabling novel light-driven synthetic transformations. Results and Discussion The reaction between 2-methylbenzophenone (1a) and coumarin (2a) was initially screened in a MFP of 1000 μL volume, using 1.5 equiv of 1a and a residence time of 26.6 min (Table 1 and Table S3 in the Supporting Information File 1

• higher MFP volume resulted in a higher productivity: 0.077 mmol·h−1 vs 0.063 mmol·h−1 (entry 1 vs entry 2, Table 1). Reversing the reagents ratio, i.e., using a slight excess of coumarin (2a), turned out to be highly beneficial, giving the cyclized product 4a in 77% yield (Table 1, entry 3). Notably, the

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• -protected reducing glucose derivative 2 gave the β-glucoside 76 with good stereoselectivity, and the respective mannose derivative 24 resulted in the pure α-mannoside 77 in good yield (Scheme 12) [56]. In a general approach to coumarin-derived inhibitors of gyrase B, a group working at Hoechst Marion

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• transformed into 4-phenylcoumarin derivatives bearing C–H, C–S, C–N, and C–C bonds at 3-position. Keywords: 3-aryl-2-propynoic acid; bromo-cyclization; coumarin; diaryliodonium triflate; O-phenylation; Introduction Coumarin is a benzo-α-pyrone and one of the typical heterocyclic compounds. The importance of

• coumarins arises from the fact that the coumarin skeleton is present in many natural products extracted from plants [1][2][3] and some of them show potent pharmacological activities, such as antidepressant [4], antimicrobial [5][6], antioxidants [7][8], anti-inflammatory [9][10], antinociceptive [11

• -ketoesters and phenols (the Pechmann condensation) [17]. Recent studies for the metal-catalyzed reactions for the synthesis of the coumarin skeleton are as follows: the Yb(OTf)3-catalyzed microwave irradiation of phenols and propynoic acids [18], the Pd(OAc)2-catalyzed oxidative cyclocarbonylation of 2

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• , dehydration and aromatization reactions. The use of ionic liquids (non-volatile solvents) over toxic organic solvents makes it an environmentally benign process [45][46]. The synthesis of isomeric tetracyclic pyrazolo[3,4-b]pyridine-based coumarin chromophores 27 and 28 was reported by Chen et al. [47

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• enamides could not be reacted with sodium sulfinates to yield the respective products. Wang and co-workers described a new method for the cyclization of phenyl propiolates with sulfinic acids, generating valuable coumarin derivatives in 2015 (Scheme 44) [81]. Visible-light irradiation of Eosin Y allows the

• reduction of tert-butyl hydroperoxide (TBHP) to form a reactive tert-butoxyl radical. After hydrogen abstraction from the sulfinic acid and subsequent radical addition to the alkyne derivative, consecutive steps for rearomatization lead to the cyclic coumarin adduct. The authors used various electron

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• phenyl ring, the 3-trifluoromethylated compounds were obtained in 50–56% yields. However, coumarins bearing electron-withdrawing groups gave yields up to 70%. As for the mechanism, the trifluoromethyl radical was generated from CF3SO2Na and Mn(OAc)3, then CF3• added regioselectively onto the coumarin to

• -workers reported the synthesis of trifluoromethylated coumarin 71 and flavone 72 with CF3SO2Na (2 equiv), the hypervalent iodine F5-PIFA (pentafluorophenyliodine bis(trifluoroacetate)) (2 equiv) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 0.6 equiv). The trifluoromethylated compounds were obtained

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• led to the displacement of triphenylphosphine. Finally, coumarin derivatives 108 were obtained in yields of 40–90% as a result of intramolecular lactonization of the intermediate fumaric acid derivatives 107 [74]. In an analogous manner, but using 3-aminophenol, 7-aminocoumarin was obtained in a yield

• Gryko and Flamigni et al. for the preparation of 6-formylcoumarin derivatives 109 that are used in the synthesis of dyads 111 consisting of coumarin and corrole units (Scheme 61). The latter synthesis took place by condensation of formylcoumarins 109 with 5-(pentafluorophenyl)dipyrromethane (110) [76

• ylides in the intramolecular Wittig reaction. Synthesis of furan derivatives via resonance-stabilized ylides in the intramolecular Wittig reaction. Synthesis of 1,3-indanedione derivatives via resonance-stabilized ylides in the intermolecular Wittig reaction. Synthesis of coumarin derivatives via

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• [59] with coumarin 1 (Φfl = 0.73 in EtOH; λex = 380 nm) [46] as a reference. Photometric and fluorimetric pH titrations were performed in Britton–Robinson buffer (see above) solution (pH 2.0, c = 15 µM), and the pH value was adjusted by addition of NaOH (2 M). After each addition step, the pH and the

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• target bond 3-partition dissection maps for 27 commonly found heterocyclic rings is given in the Supporting Information File 1 (see Schemes S6 to S32). These include benzimidazole, 2,3-dihydro-1H-benzo[b][1,4]diazepine, benzofuran, benzopyran, chromen-4-one, coumarin, cyclopent-2-enone, furan, Hantzsch

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• contain two biologically important structural scaffolds, namely the 3-hydroxyoxindole and coumarin, which could be potentially used for further biological evaluation or serve as starting points in drug discovery pursuits. A highly stereoselective Mukaiyama–aldol reaction was reported by Zhou and co

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• cytotoxic activity. They can regularly be found in improperly stored food, hence, entering the food supply chain [6]. Further coumarin derivatives, e.g., umbelliferone (4), esculetin (5), and scopoletin (6), are subject of investigation due to their pharmacological properties, i.e., anticancer effects

• the coumarin derivatives umbelliferone (4, Figure 1), esculetin (5, Figure 1), and scopoletin (6, Figure 1) are subject of anticancer research [67]. Marmesin (62) was first isolated from the fruits of Ammi majus [67], and is currently under investigation as an agent for the treatment of angiogenesis

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• bioavailability of anticancer drugs. Thus, SuberAniloHydroxamic acid–cholesterol conjugates (SAHA–cholesterol) [11], cholesterol-based charged liposomes encaging doxorubicin [12] or curcumin [13] showed higher activity compared with the native drugs. Synthetic coumarin-caged cholesterol derivatives, for instance

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• (umbelliferone) (9) upon ring-closing metathesis. The synthesis of coumarin derivatives using this approach was described in previous publications [20][21]. By introducing an electron donor in the 7-position, a fluorescent product is obtained upon ring-closing metathesis [22]. Synthesis of the profluorescent

• (cooled at 5 °C to minimize evaporation) was pipetted. Then, 5 µL of a 3 mM precatalyst stock solution was added. Finally, 3 µL of the substrate stock solution was added (for the coumarin substrate 8 a 1 M stock solution was used, for the fluorophore quencher substrate 5, a 50 mM stock solution was used

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• prepared either in well water-soluble form or as gels of high swelling. Two versatile synthetic strategies for introducing a fluorescent tag (rhodamine, fluorescein, nitrobenzofuran or coumarin) into the water-soluble epichlorohydrin branched cyclodextrin polymers were worked out and compared. The

• techniques and capillary electrophoresis. The applied synthetic routes were evaluated based on the molecular weight, cyclodextrin content of the products and the efficiency of labeling. Keywords: coumarin; fluorescein; functionalized monomers and polymers; nitrobenzofurazan; rhodamine; Introduction

• , we report the controlled, regioselective fluorescent labeling of neutral and cationic epichlorohydrin branched β-CD polymer with four different dyes (rhodamine, fluorescein, coumarin and nitrobenzofurazan). Our goal was the development of versatile synthetic strategies, yielding key intermediates of

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• propensity to undergo heterolytic photosolvolysis reactions, most notably o-nitrobenzyl (o-NB) [12], benzyl phenyl ketone (benzoin) [13][14], coumarin-4-ylmethyl [15], and, more recently, p-hydroxyphenacyl (pHP) [15] phosphate esters (Figure 1). While these chromophores exhibit a range of photophysical

• enzymatic studies of ATPase [28][29][30][31][32][33][34]. We [15][28][29][35] and others [6][7][8][9][10][11] have successfully offered alternatives to the o-NB PPG series, initially with benzoin phosphate 2 [13][14] and coumarin-4-ylmethyl phosphate 3. However, the chromophores for these candidates remain