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

• dihydropyridine, hydantoin, imidazole, indole, isoquinoline, isoxazole, oxazole, 4H-pyran, pyrazine, pyridazine, pyridine, pyridinone, pyrimidine, pyrimidone, pyrrole, 3H-quinazolin-4-one, quinoline, 1H-quinolin-4-one, and thiophene. For heterocycles that are composed of a fused aromatic ring, such as

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• (see Figure 3, Figure 4 and Supporting Information File 2 for details of X-ray study of compounds 4a,o,p). According to the XRD data, the molecules of compound 4a are non-planar with the Ph substituent turned toward the oxazole ring by a 51° angle and the imidazole ring turned toward the oxazole moiety

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• enantiopure phosphine catalyst 27 in order to generate the coupled product 30 with both high ee and dr (Scheme 6) [31]. Presumably, the allenyl stereochemistry is destroyed upon 1,4-addition of the phosphine catalyst, resulting in chiral phosphonium adduct 29 that further reacts with deprotonated oxazole 28

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• pathways but is found across proteins of all sizes so will not be discussed here. Review Thiazole and oxazoles Thiazoles and oxazoles are found in a huge number of bacterial RiPPs, which are often loosely defined as thiazole/oxazole-modified microcins [24] (TOMMs), although these can be subdivided more

• there remains a wealth of unexplored pathways to discover and characterise. Schematic of RiPP biosynthesis. Thiazole/oxazole formation is represented by the blue heterocycle (X = S, O), lanthionine formation is represented by the purple cross-link (X = S) and macrolactam (X = N) or macrolactone (X = O

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• formed. Instead, we isolated the trisubstituted oxazole derivative 6 in 55% yield. The scope of this reaction has not been studied by us, however it is known in the literature that enamides can undergo related oxidative cyclizations to oxazoles in the presence of the reagent cocktail employed or under

• methoxylation of compound 3a we unexpectedly observed the formation of the 5-acetyl-substituted oxazole derivative 6. However, precursor 3i was smoothly available from acetylacetone 1a. It could smoothly be transformed into the desired bipyridine derivative 4i, but also into the related pyrimidine and

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• Na a174 yielded a new class of halogenated pyrrole–oxazole compounds 14–18 (Figure 8). Pyrronazols A (14), A2 (15) and B (16), synthesized by Ari7, additionally include an α-pyrone moiety [48]. This is worth noting, since the non-cyclic alkyl moiety in the pyrronazols C1 (17) and C2 (18), found in

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• exhibit an unusual molecular architecture featuring two oxazole rings connected by a two-carbon tether and a terminal 2,4-pentadienylamine moiety. Feeding experiments as well as biosynthetic reasoning indicated that the siphonazoles originate from a mixed PKS/NRPS pathway [125]. Both bisoxazoles were

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• functionalization with nitrogen nucleophiles, including amides, sulfonamides and primary arylamines. In addition, the oxazole-based DG could be easily deprotected to provide the corresponding benzoic acid 44 by heating in EtOH in the presence of KOH (Scheme 13). As another easily available N-containing aromatic

• , was reported by Dai and Yu et al. [83]. As outlined in Scheme 26, the presence of the oxazole-based DG was found to be the main factor in tuning the selective formation of 101. Related control experiments suggested that the formation of intermediate 102 acquired from the copper-catalyzed C(sp2)–C(sp3

• for lactam synthesis. Copper-catalyzed amidation/sulfonamidation of aryl C–H bonds. C–H amidation of pyridinylbenzenes and indoles. Mechanism of the Cu-catalyzed C2-amidation of indoles. Copper-catalyzed, 2-phenyl oxazole-assisted C–H amidation of benzamides. DG-assisted amidation/imidation of indole

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• . This is illustrated with one reaction in which 3 was subjected to treatment with triphenylphosphine in the presence of iodine and triethylamine in dry dichloromethane at room temperature (Scheme 4) [34][35]. As expected, compounds 3 are converted to 2,4,5-substituted oxazole 7 regiospecifically in good

• investigation of the structure of 8a indicated that the compound is a highly substituted 2-(trifluoromethyl)oxazole. With different α-azidochalcones, differently substituted 8 have been isolated (Figure 5). It should be mentioned that oxazole formation is observed only at low temperature with trifluoroacetic

• , the solvent was removed in vacuo, and the residue was directly purified by column chromatography on silica gel (hexane/ethyl acetate 9:1) to yield oxazole 7. Synthesis of 8: In a dry two neck round bottom reaction vessel equipped with a calcium guard tube and a magnetic bar, α-azidochalcone (1.0 equiv

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• naphthoquinones (Figure 1) such as naphtho[2,3-b]furan [5][6][7][8][9][10][11][12][13][14], naphtho-pyran [15][16][17][18], benzo[f]indole [19][20][21][22][23][24], benzo[g]quinolone [25], benzo[b]carbazole [26], naphtho[2,3-b]thiophene [27][28][29][30][31][32][33] and naphtho[2,3-b]]oxazole [34] have been

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• -azabicyclo[3.2.1]oct-2-ene and/or 5,7-dioxa-1-azabicyclo[4.3.1]deca-3,8-diene-2-one derivatives. According to DFT calculations (B3LYP/6-31+G(d,p)), the cycloaddition can involve two modes of nucleophilic attack of the dihydroazireno[2,1-b]oxazole intermediate on acetyl(methyl)ketene followed by aziridine

• the mechanism of trapping of dihydroazireno[2,1-b]oxazole intermediates by acetyl(methyl)ketene were investigated by the DFT method. Results and Discussion Rhodium(II) carbenoids generated from α-diazoketones or 2-diazo-1,3-diketones react with various nitrogen-containing compounds, such as amines [16

• involves the 1,5-cyclization of azirinium ylide 9f–h to dihydroazireno[2,1-b]oxazole 10f–h followed by cycloaddition of the latter to ketene 12 to give two regioisomeric adducts 6f,g and 7f–h (Scheme 3). Several examples of the 1,5-cyclization of azomethine ylides bearing an α-keto group into oxazole

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• solvent mixture at 100–110 °C for 18 h. The oxazole moiety also acts as the directing group in the acetoxylation of alkyl groups with Pd(OAc)2/AcOOt-Bu or Pd(OAc)2/lauroyl peroxide oxidative systems; in these reactions acetic anhydride served as the source of the acetoxy groups [88]. Recently, Cu(OAc)2

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• solution and dichloromethane is employed as electrolyte. The method features attractive yields (70–95%) and a broad scope with regard to substitution on the phenylene moiety (R1 and R2) and on the oxazole unit (R3). 2 Intermolecular cyclizations 2.1 Cycloadditions with anodically generated intermediates A

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• .10.230 Abstract Novel cis/trans-4- and cis/trans-5-(2-vinylstyryl)oxazoles have been synthesized by Wittig reactions from the diphosphonium salt of α,α’-o-xylene dibromide, formaldehyde and 4- and 5-oxazolecarbaldehydes, respectively. In contrast, trans-5-(2-vinylstyryl)oxazole has been synthesized by

• )oxazole small quantities of electrocyclization product, 4-(1,2-dihydronaphthalen-2-yl)oxazole, are isolated and spectroscopically characterized. Keywords: bicyclo[3.2.1]octane; intramolecular photocycloaddition; oxazole; styryl; vinyl; Introduction The bicyclo[3.2.1]octane skeleton is the basic

• ] and sydnones [11][12][13], as routes to polycyclic compounds, we turned our attention to oxazole derivatives. The oxazole structure is commonly found in natural products and pharmaceuticals [14][15][16][17] and is applied in useful reagents and intermediates in organic synthesis [18][19][20][21][22

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• very low activation barriers (0.2–1.5 kcal/mol) to give (3Z)-1-oxa-5-azahexa-1,3,5-trienes. This is expected, because the oxazole N–O bond is very weak and the reaction is pseudopericyclic [21][22]. The calculated low thermodynamic and kinetic stabilities of the isoxazolium ylides (Figure 1) give only

• )] computed at DFT B3LYP/6-31G(d) level. Energy profiles for the transformations of (3Z)-1-oxa-5-azahexa-1,3,5-triene D and oxazines E derived from (methoxycarbonyl)phenylcarbene or di(methoxycarbonyl)carbene and oxazole A. Relative free energies [kcal/mol, 298 K, CH2Cl2 (PCM)] computed at DFT B3LYP/6-31G(d

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• afforded the final (R)-bacillamide C in 6% yield over three steps (ee 94%). Oxazoles The oxazole unit has been applied in different bioactive marine natural products [110]. The group of Zhu reported a Ugi 3-CR to a small library of 2,4,5-trisubstituted oxazole-containing peptide-like structures from

• bifunctional α-isocyanoacetamides (Scheme 43) [111][112]. A plausible mechanism for this reaction involves the formation of 141, that after tautomerization, cyclizes to the oxazole product 143. It is noteworthy, that this reaction proceeds without the addition of a carboxylic acid because amino-oxazoles are

• unstable under acidic conditions. In total, six different aldehydes, twelve amines and three isocyanides yielded the corresponding desired oxazole mimics 143 in good yields (60–96%), however, the products were obtained as racemates even when the reaction was performed with chiral isocyanides. Some

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• reaction with the chloride ion released during the initial imine acylation. Finally, a combination between Brønsted acid and metal catalysis, promote the isomerization of V to oxazole 21. It is noteworthy, that the gold catalyst seemed to be essential only for the formation of the gold-acetylide

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• 13C NMR signals of oxazole C-5 (10 Hz) and C-4 (6.2 Hz). To the best of our knowledge, this is only the second time that a peptide-derived oxazol-5-ylphosphate has been characterized. Earlier, Boyd and co-workers had converted an oxazolone to an oxazolyl phosphate by treatment with excess diphenyl

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• oxazole or thiazole rings) [10], papuamides (HIV inhibitory macrocyclic depsipeptides) [11], polytheonamides (cytotoxic linear polypeptides) [12], cyclotheonamides (thrombin and serine protease inhibitors) [13], perthamides (anti-inflammatory cyclopeptides) [14][15], solomonamides [16] and

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• cell line and >400-fold selective over both the NF-κB activation in HEK 293T cells and against TNFα-mediated NF-κB activation. In comparison, the second oxazole-based probe 12 is also potent (0.2 μM) in the 697 pre-B cell line and >400-fold selective over both the NF-κB activation in HEK 293T cells and

• 4-ethoxybenzaldehyde was condensed with diacetyl monoxime under acidic conditions. The resulting oxazole N-oxide 9 was converted to the chloromethyloxazole 10 via selective chlorination with phosphorous oxychloride in good yield. Addition of thioglycolic acid led to the carboxylic acid 11, which was

Synthesis of 5-(ethylsulfonyl)-2-methoxyaniline: An important pharmacological fragment of VEGFR2 and other inhibitors

• Miroslav Murár,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2013, 9, 173–179, doi:10.3762/bjoc.9.20

• sodium salt C was subsequently converted to the hydrochloride salt of 3-amino-4-hydroxybenzene-1-sulfonyl chloride (D) by treatment with thionyl chloride at room temperature. The amino group of D was protected in the form of a 2-methylbenzo[d]oxazole-5-sulfonyl chloride (E) by reaction of D with (EtO)3CH

Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization

• Piyush K. Agarwal,
• Meena D. Dathi,
• Mohammad Saifuddin and
• Bijoy Kundu

Beilstein J. Org. Chem. 2012, 8, 1901–1908, doi:10.3762/bjoc.8.220

• antagonistic [4] and antitopoisomerase-I activities [5][6][7][8][9][10][11][12][13][14][15][16]. The presence of a heterocyclic ring at the position 3 of the indole represents an important class of marine alkaloids, such as oxazole (martefragin [17], amazol [18]), imidazole (topsentins [19][20] and

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• , 4.25; N, 23.75. Terphenyl scaffold 1 [13][14]; oxazole-pyridazine-piperazine 2 [14][15] and aryl-triazoles 3 and 4 [15][16] as α-helix mimetics. Synthesis of azido-functionalized resins 7 and 9. Copper-catalyzed [2 + 3] cycloadditions of resin-bound azide 7 with five terminal alkynes. Copper-catalyzed