Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• in S. cinnamonensis [15][16][17][18][19][20], but much remains to be learned about the timing of the various steps of oxidative ring formation (and hence the true nature of the enzyme-bound intermediates) and about the exact role of the enzymes involved in these late steps. As shown in Scheme 1, the

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• optimal experimental conditions already reported with triazines [22][23][24]. In chlorobenzene at 220 °C (optimal reaction temperature for six-membered-ring formation), the corresponding cycloadducts 10–13 were obtained in high yields (Scheme 4, Table 3). We therefore developed an efficient method for the

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• peroxide moiety, the Isayama–Mukaiyama peroxysilylation, and reactions involving peroxycarbenium ions. Syntheses employing hydrogen peroxide and the intramolecular Kobayashi cyclization are less frequently used. 1.1. Use of oxygen for the peroxide ring formation The singlet-oxygen ene reaction with alkenes

• -ene (148) (Scheme 35). The cyclization occurs selectively because the hydroperoxide group in intermediate 147 attacks only one of two possible electrophilic carbon centers [266]. 1.5. 1,2-Dioxolane ring formation through oxidation of the allylic position 1,2-Dioxolane-containing compounds 150a–d were

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• provide a steady tool for the ring formation of 4,4-spirocyclic γ-lactams with the incorporation of CO as a carbonyl group. Experimental Typical procedure for a construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with CO: A magnetic stirring bar, 2-(azidomethyl)-N-benzyl-N-(2

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• and molecule types have been used depending on the desired geometry, such as ring formation [9], carbohydrate–triazole conjugation [10], aryl–alkyne linked structures [11][12][13][14][15] and the use of DNA as a rigid bridge between silver nanoparticles and quantum dots [5]. Among the rigid linking

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• -annulation cascade reaction with N,N-(dialkylamino)benzaldehydes, a process in which a 1,5-hydride shift occurs followed by larger ring formation [16]. After the evaluation of different Brønsted acid catalysts, diphenylphosphate (20 mol %) was identified as a suitable catalyst for the reaction. Toluene again

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• transformations and easily separated after the cycloadditions. Whilst the cycloadditions described above demonstrate the preference for the dipolarophile installed at module 3, we then attempted to alter the cyclization mode (module 3→4) by increasing the entropic barrier for medium-sized ring formation (Scheme 4

• formation of a seven-membered ring. Despite the minor pathway, cycloaddition at module 4 also competed to give 54 in 22% yield. On the other hand, cycloaddition of 52 exclusively occurred with the indole group at module 4, giving rise to 56 in 94% yield without eight-membered ring formation leading to 55. X

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• δ-lactam ring formation) is irreversible, there are at least three possible explanations for the high diastereocontrol in the formation of 1a–j and 2a–l: - The first is that the nitro-Mannich step is highly diastereoselective and lactamisation occurs subsequently without any effect on the

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• -protection gave the alcohol 12 which was oxidized to aldehyde 8a. Cascade condensation, cyclization, cycloaddition The cascade tricyclic ring formation was then investigated with the aldehydes 6, 8a and 8b. Heating aldehyde 6 with glycine gave a mixture of unidentifiable products. However, heating with

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• responsible for uracil ring formation, although biochemical evidence is currently missing. The final hydroxylation step towards cylindrospermopsin has been shown to be catalyzed by CyrI, a 2-oxoglutarate-dependent iron oxygenase [31]. Interestingly, two epimers were described for the corresponding hydroxyl

• halogenated by unique biochemical mechanisms through the two non-heme iron(II)-dependent halogenases BarB1 and BarB2 (Figure 6A) [40]. Further extraordinary features of the pathway include one-carbon truncation during chain elongation, E-double bond formation and thiazole ring formation. Jamaicamide The

• substituent, a beta-methoxy eneone system, and a pyrrolinone ring [41]. The incorporation of the chlorovinylidene group was partially elucidated and predicted to be highly similar to the cyclopropane ring formation of curacin A biosynthesis (Figure 6B) ([42], see below). The enzyme cassette comprises a PKS

Intramolecular hydroamination of alkynic sulfonamides catalyzed by a gold–triethynylphosphine complex: Construction of azepine frameworks by 7-exo-dig cyclization

• Hideto Ito,
• Tomoya Harada,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2011, 7, 951–959, doi:10.3762/bjoc.7.106

• intramolecular hydroamination of alkynes [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], seven-membered ring formation is rare and is limited to the cases where the substrate is preorganized for cyclization: The substrates must

• triethynylphosphine ligand L1 was also evaluated for the eight-membered ring formation of sulfonamide 9, which is much more challenging than the seven-membered ring formation of 4. The reaction required 5 mol % catalyst loading under heating conditions (80 °C) in 1,2-dichloroethane for a reasonable conversion rate to

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• . Its synthesis, as well as that of its dihydroxylated homologue 36, features as the key step five-membered ring formation via RCM induced by the 2nd-generation Grubbs catalyst 5 (Scheme 6) [58]. A further contribution to new pyrrolidine-based azasugars, characteristically having 1,2-dihydroxyethyl side

Novel carbazole–pyridine copolymers by an economical method: synthesis, spectroscopic and thermochemical studies

• Aamer Saeed,
• Madiha Irfan and
• Shahid Ameen Samra

Beilstein J. Org. Chem. 2011, 7, 638–647, doi:10.3762/bjoc.7.75

• monomers. i) R–Br, 50% KOH, benzene, TBAB, 80 °C, 2 h; ii) AcCl, AlCl3, CHCl3, 0 °C then rt, 3 h. Synthesis of poly[3,6-N-alkylcarbazole-4-(3-substituted phenyl)pyridine-2,5-diyl]. i) CH3COONH4, CH3COOH, reflux, 18 h. Proposed mechanism of pyridine ring formation. Thermal data and molecular weights for

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• first results on the direct alkynylation reaction combined in a one-pot procedure with gold-catalyzed indole ring formation are promising, and analogous strategies combining palladium-catalyzed synthesis of indoles [3] and gold-catalyzed alkynylation could also be envisaged. The next step will be to

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• indole ring formation (Scheme 11) [13]. As can be seen from Scheme 11 the indole 59 prepared via the Japp–Klingemann reaction is substituted at position 2 by an ester group which prevents reaction with electrophiles, thereby reducing the amount of undesired by-products. A simple sequence of hydrolysis

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

Synthesis of new C^α-tetrasubstituted α-amino acids

• Andreas A. Grauer and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 5, doi:10.3762/bjoc.5.5

• from commercially available racemic methionine in a four step synthesis. TAAs show the ability to induce stable β-turns in solid state and solution when incorporated into natural peptide sequences [20]. The key step of the TAA synthesis is the ring formation, which is an aldol type reaction between the

• improve the diastereoselectivity of the ring formation. n-Butyraldehyde (2) was chosen for the first set of reactions to optimize the reaction conditions. Table 1 summarizes the results. In total eight different reaction conditions were tried and the conversion was determined by 1H NMR analysis after

• aldehyde was reacted with the sulfonium salt 1. The corresponding TAA was obtained in 18% yield. To investigate the reactivity of ketones, acetone (9) was tested but no TAA product was formed. The diastereoselectivity of the reaction was also examined. The previously reported ring formation reactions with

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• so efficiently furan ring formation was investigated with ketone 30. Three general protocols were identified as suitable for attempting fused furan formation with substrate 30; 1) Padwa [20] and Mukaiyama [21] furan synthesis, 2) Nishizawa furan synthesis [22], and 3) classical acid catalysed

Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate strategy

• Asunción Barbero,
• Francisco J. Pulido and
• M. Carmen Sañudo

Beilstein J. Org. Chem. 2007, 3, No. 16, doi:10.1186/1860-5397-3-16

• silylcuprate with electrophiles ("the silylcuprate strategy") provides new routes for the synthesis of functionalised allylsilanes, which undergo highly stereocontrolled silicon-assisted intramolecular cyclizations leading to three to seven membered ring-formation. Background Organosilicon compounds and in

• groups in appropriate positions undergo silylcupration-ring formation, when treated with higher order cyanocuprates as (PhMe2Si)2CuCNLi2. Intramolecular trapping of the vinylcuprate intermediate allows the synthesis of methylenecyclopentanes 20–22 (Scheme 4). [14] Epoxidation of the oxoallylsilanes

• -cyclopropane moiety, from open chain allylsilanes in just one step. The high stereocontrol associated to the ring formation allows the synthesis of enantiomerically pure spiro-tricyclic alcohols containing an angular OH-group, such as 38 (Scheme 7). [20] The use of reagents different from organoaluminun

Microwave- assisted ring closure reactions: Synthesis of 8-substituted xanthine derivatives and related pyrimido- and diazepinopurinediones

• Joachim C. Burbiel,
• Jörg Hockemeyer and
• Christa E. Müller

Beilstein J. Org. Chem. 2006, 2, No. 20, doi:10.1186/1860-5397-2-20

• a versatile condensing agent in heterocyclic ring formation [21][22]. However, its very low polarity can cause solubility problems when polar compounds are to be reacted. High temperatures (>120°C) and long reaction times (from several hours to several days) are generally required for the synthesis

• poor mixing. Microwave-assisted synthesis has been extensively applied in the field of heterocyclic chemistry, especially when high temperatures are needed for ring formation with conventional heating [24]. Based on these findings the preparation of 8-substituted xanthine derivatives and related

The vicinal difluoro motif: The synthesis and conformation of erythro- and threo- diastereoisomers of 1,2-difluorodiphenylethanes, 2,3-difluorosuccinic acids and their derivatives

• David O'Hagan,
• Henry S. Rzepa,
• Martin Schüler and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2006, 2, No. 19, doi:10.1186/1860-5397-2-19

• benzylic as well as anchimeric stabilisation via phenonium ring formation 18 with the β-phenyl group as illustrated in Scheme 6. Isolation of the minor threo-13 isomer required careful chromatography. In order to improve the synthesis of threo-13 a reaction with cis-stilbene 17 was investigated. The one

Crystal engineering of analogous and homologous organic compounds: hydrogen bonding patterns in trimethoprim hydrogen phthalate and trimethoprim hydrogen adipate

• Packianathan Thomas Muthiah,
• Savarimuthu Francis,
• Urszula Rychlewska and
• Beata Warżajtis

Beilstein J. Org. Chem. 2006, 2, No. 8, doi:10.1186/1860-5397-2-8

• identical with TMP-dicarboxylate salts such as TMP-hydrogen glutarate [17] and TMP-succinate [29] but differ only in the number of carbon atoms of the chain. Such cyclic hydrogen-bonded ring formation blocks the base-pairing interaction between the pyrimidine moieties. Hence base-pairing has not been