Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• -Hydrazinylpyridines (a) and pyridinylhydrazones (b), as well as their acylated derivatives (c), are versatile scaffolds for the preparation of triazolopyridines (Scheme 1). The known methods for the [1,2,4]triazolopyridine ring formation use various condensation agents such as HCOOH, orthoesters, Lawesson’s reagent

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

• Antonella Di Vincenzo,
• Antonio Palumbo Piccionello,
• Alberto Spinella,
• Delia Chillura Martino,
• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• . Formation of the 1,3-oxazinan-2-one ring. Formation of the product at m/z 382.2765 u. Formation of the components of mixture I. Percent of absorbed guest in the sequestration tests.a Supporting Information Supporting Information File 332: Possible structures of the components present in the mixtures

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• multiplication and viability of bacteria, and second, they are highly conserved in many bacterial species [85]. Various studies have shown that Z interaction protein A (ZipA) is one of the essential components that stabilize the Z-ring formation and that it binds to FtsZ with high affinity. The interaction

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• stereoselectivity of the ring-formation step can be explained by the suprafacial addition of the allene to the double bond of the α,β-unsaturated compound 4, the diastereoselectivity being sterically controlled by the methyl group on the β-face. The transformation of the vinylsilane moiety in 5 into the

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• in the order of the oxazoline ring formation and the aryl transfer steps. In our model transformation, it was found that the reaction generally features the aryl transfer–ring closing sequence and this sequence shows very limited sensitivity to the variation of the substituent of the reactants. On

• Scheme 2 and Scheme 3) the ring formation takes place with an activation free barrier of 22.6 kcal/mol (TSrcA). Along this path this is the rate determining step. The calculations revealed that once the ring is formed, the aryl transfer spontaneously occurs and a significant amount of free energy is

• amount free energy to arrive at the same state as postulated for path A. Comparison of the two free energy profiles indicates that the preferred route is the one where the aryl transfer precedes the oxazoline ring formation. On the other hand, the calculated activation free energy barriers are compatible

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• (compound 23) is shown in Figure 9, which involves installing an allyl group at C1' (20) and converting the C2'–CN to an aldehyde (21) followed by a Wittig reaction to install a second allyl group at C2' (22). Second generation Grubb’s catalyst was used for the ring formation, followed by hydrogenation to

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• precursors in a multistep sequence prior to indole ring formation [7]. In order to address these potential shortcomings we set out to develop a benign process relying on inexpensive substrates and non-toxic reagents that would rapidly deliver the desired indole in a readily scalable and continuous fashion

• looked at telescoping the final two steps of the process; substitution of the ethoxy group by hydrazine and then ring formation to the 3H-[1,3,4]oxadiazol-2-one unit [32][33]. In this procedure a 0.95 M THF solution of compound 12 was united with a solution of hydrazine (1.0 M in THF) and directed into a

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• -ring formation was investigated in non-activated systems, 5,7,8,13-tetrahydro-6,13-methanodibenzo[c,f]azonine was exclusively obtained. Furthermore, selective ring closure in the para-position could be achieved under standard PFB conditions, while a double ring closure could be obtained utilizing HClO4

• function of the water content of the reaction mixture. An acetal concentration of 0.3 M proved optimal to minimize the ether formation. The PF reaction conditions could possibly lead to a competition between 6-membered and 5-membered ring formation in systems such as 9a,o,p (Scheme 6). For this study

• cyclized into the indole 16p. It is thus possible to infer that indole formation is highly disfavored and only the presence of a great number of activating groups can make this outcome competitive. We then decided to expand our analysis to include competition between 6- and 7-membered ring formation

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• , selective synthesis of benzo-fused six- or five-membered rings can be achieved. We have demonstrated that the 5-membered ring formation is favored, when the two processes are competitive, and we have also shown that acetonitrile can act as a third component in the cyclization to oxazepinones. By employing

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• formation. Further we speculated that compound 26, in the presence of a base, might undergo a simultaneous epoxidation–intramolecular epoxide-ring opening to produce 27 (Scheme 7) as the corresponding benzoxepin ring formation via intramolecular displacement of –OTs group by ArO− is unresponsive [23]. To

• , may produce traces to significant amounts of side-products via hydrogenolysis. Thus, we decided to modify Panda’s synthetic route to significantly increase the overall yield. We hypothesized that this problem might be circumvented by performing the debenzylation reaction prior to the epoxide-ring

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties

• Maximilian Maier,
• Magnus S. Schmidt,
• Markus Ringwald and
• Christoph P. Fik

Beilstein J. Org. Chem. 2017, 13, 372–383, doi:10.3762/bjoc.13.40

• finger print regime, we can only assume that all three propagation pathways a), b) and c) take place simultaneously. Furthermore, taking in account FTIR and DSC data, we expect that ring formation significantly contributes to the overall reaction enthalpy. It is quite clear, that the combination of

• thus highest apparent network density. This means that ring formation, which in principle should reduce the amount of covalent network points in the cured material, is superimposed by effects of conversion, entanglement and rigidity of the formed polymer. The decreasing trend of flexural modulus from 1

• intramolecular arrangement and the substitution with N-allyl, N-acyl and N-acrylamide functional groups. Surprisingly, the contribution of internal N-allyl groups was higher than that of external ones indicating a dominant, non-classical polymerization mechanism. The results support exothermic ring formation on

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• position of its indole ring. Conclusion The posttranslational isoprenylation of tryptophan involving pyrrolidine ring formation was first discovered in a B. subtilis peptide pheromone, as a crucial modification for the pheromonal function. In addition, the discovery of the ComXnatto pheromone revealed that

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• catalysing C-O-D ring formation and that this activity relies on interactions with the non-ribosomal peptide synthetase via the X-domain. Despite the interaction of StaF with the A47934 X-domain being weaker than for the preceding Oxy enzyme StaH, StaF retains higher levels of in vitro activity: we postulate

• show that the substrate specificity of StaF is not as broad as for Oxys catalysing the C-O-D ring formation, in agreement with the results from OxyAtei. Additionally, we could show that StaF interacts with the A47934 X-domain, indicating that StaF is, along with other related Oxy enzymes, recruited by

• appropriate MWCO. 2) Subsequently, the activity assay is performed using StaH and StaF together with the redox system composed of palustrisredoxin reductase (PuR), palustrisredoxin B A105V (PuxB) and NADH, in which StaH catalyses C-O-D ring formation between D-Hpg4 and L-Tyr6 and StaF catalyses ring D-O-E

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• prevent 5-membered ring formation by this group. The cis-dihydroxy groups in position 3 and 4 of compound 2 were acetylated (→ 12) prior to the deprotection of the anomeric center. Following this sequence, allyl 3,4-di-O-acetyl-2-O-methyl-α-L-fucoside (12) was synthesized in 50% yield over four steps from

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

• characterised in the pederin (24) and the ambruticin (28) biosynthetic pathways (Scheme 3 and Scheme 4) [14][15]. PedPS7 is a monofunctional pyran synthase (PS) domain that was predicted to catalyse ring formation from an α,β-unsaturated intermediate in the biosynthesis of the PKS–NRPS hybrid product pederin

• polyketide with potent antitumor, antifungal, antiparasitic, pesticidal and antitrypanosomal activities (Scheme 13). In its biosynthesis, the furan-ring formation occurs on a late stage, catalysed in an unprecedented fashion by the cytochrome P450 oxidase AurH [13][62][63][64][65][66][67]. This enzyme

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• carbenes and nitrenes generated from sulfonate esters prefer 6-membered ring formation (i.e., 1,6-insertion) opened the door for easy access to 1,3-functionalized products via C–H insertion [64][65]. The sulfonate can be a useful functional group for subsequent transformations, also. If used in the

• profound effect on the preferred C–H insertion location (Scheme 14). As has been noted for other intramolecular insertions [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65], five-membered ring formation is generally preferred over other ring sizes. Thus, the

• sterically hindered catalyst such as Rh2(esp)2 or Rh2(OPiv)4 is needed to prevent dimerization of the diazoacetate. These catalysts are presumed to protect the carbene intermediates from intermolecular reactions long enough to adopt the correct conformation for bridged-ring formation. An exploration of the

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• reductive steps are optional in PKS biosynthesis, and considering the pyrone ring formation, an unsaturated PKS chain residue attached to the carrier is essential. This general PKS catalyzed mechanism is accomplished by different enzymatic machineries. In the following section the three PKS types which can

• investigated in detail. In vitro assays using NAC thioesters of the western and eastern chains in the biosynthesis of 36 [88], as well as simplified substrate mimics of both antibiotics [88][89] provided experimental evidence that the free-standing ketosynthases are responsible for the α-pyrone ring formation

• substrates, i.e., this resulted in a 12-fold increase of product formation. This is an additional hint that protein–protein interactions represent an important factor in PKS systems. Further, it seemed that the carrier proteins conferred specificity for α-pyrone ring formation, since once the carrier

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• : benzimidazolium salts; bulky ligands; cyclization; ligand design; N-heterocyclic carbenes (NHC); ring formation; Introduction Imidazole-based N-heterocyclic carbenes (NHCs) are stable systems serving as ancillary ligands mainly to construct organometallic complexes. These NHCs are sterically and electronically

• and 4-Cl the synthetic procedures proceed without noticeable problems, while complications were faced in the synthesis for 1-Cl and 2-Cl, particularly during the benzimidazole ring closures. Excluding the procedure of Borguet [42][43] all the known procedures to accomplish imidazole ring formation [44

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• ethynylene)s comprising a cinnoline core were prepared in high yields via a three-step methodology. A Richter-type cyclization of 2-ethynyl- and 2-(buta-1,3-diynyl)aryltriazenes was used for cinnoline ring formation, followed by a Sonogashira coupling for the introduction of trimethylsilylethynyl moieties

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• barriers of quaternary carbon and six-membered ring formation. The use of the second nucleophile and a fast initial trapping reaction reduced the cation character of the radical cation intermediate, slowed competitive elimination reactions, and allowed for the desired quaternary carbon formation. In these

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• . The TS 9‡ corresponds to the initial nucleophilic attack onto the nascent carbodiimide and is located at 14.9 kcal mol−1 whereas the introduction of solvent reduces the barrier to 9.9 kcal mol−1 (Scheme 3). There are two possible pathways for the MeSO2Cl assisted 1,2,4-thiadiazole ring formation

• , namely cyclization-IIa and cyclization-IIb (Scheme 2). It was very difficult to locate 14‡ in cyclization-IIa, the transition state for the second heterocyclic ring formation, due to a complex reaction coordinate (Figure 3). We were only successful considering that it may be promoted by a proton binding

• locate the DMAP-assisted TS for 1,2,4-thiadiazole ring formation via cyclization-IIb due to a complex reaction coordinate. Conclusion We report on a straightforward methodology to prepare three substituted benzimidazole-fused 1,2,4-thiadiazoles via a methanesulfonyl chloride assisted cyclization between

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

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

• electrochemical construction of heterocycles have been reported in recent years. These cases demonstrate that ring formation can be achieved efficiently under ambient conditions without the use of additional reagents. In order to account for the recent developments in this field, a selection of representative

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• groups since previous RCM studies [33] showed that the productive RCM for 8-membered ring formation was observed only for the S,S- configured trienes in the presence of an exo-methyl group at the allylic position (Figure 1). Initial attempts were focused on generating the first set of five polyols

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• the pyrazolo[4,3-c]pyridine system can be mainly achieved through two different approaches. One strategy involves the annelation of a pyrazole ring onto an existing, suitable pyridine derivative [16]. Alternatively, the bicyclic system can be accessed by pyridine-ring formation with an accordant

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• complex products and bioactive compounds. Among the glycosans, the anhydro sugars involving the anomeric center in the ring formation, the 1,6-anhydro sugars are the most common and useful building blocks [1][2]. They can play a role in synthetic methodologies aiming at the obtainment of regioselectively