Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• ), which is subsequently converted to I–C intermediate D via radical migration [88]. The homogeneous cleavage of the C–I bond in D leads to the stable carbon radical E and an iodine radical. Finally, the reaction between E and the iodine radical produces product 2a, with the concomitant release of water

• and iodobenzene. In pathway b, the O–I intermediate C is converted to a C–I intermediate D via 1,3-migration [89]. Then, intermediate D carries through a five-membered ring transition state F to afford the title product 2a, accompanied by the release of iodobenzene and water. One practical application

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• signalling pathway has been shown to regulate crucial aspects of cell fate determination, organogenesis, cell migration and polarity [1]. Importantly, compromised Wnt signalling has been implicated in the perturbation of synaptic integrity and function in Alzheimer’s disease (AD) [2]. Palmitoleoylation of

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• explain odd results from Friedel–Crafts reactions [19] and this type of process is sometime referred to as a Baddeley rearrangement. Many examples of alkyl group migration have been described [19]. Phenyl groups migrate easily and degenerate phenyl shifts in biphenyl were confirmed by isotopic labeling

• present work, we have explored rearrangements of quaterphenyls, the next homolog in the paraphenylene series, now with six structural isomers. Scheme 2 summarizes interconnections via 1,2-migration of a terminal phenyl group. As will be shown below, an internal aryl–aryl bond can also be transposed

• through 1,2-biphenyl migration, with a similar network of interconversions. Based on the behavior of terphenyl which favors meta substitution at equilibrium, we initially hypothesized that m,m'-quaterphenyl (14) would likely be the major isomer at equilibrium. Only brief exploration of quaterphenyl

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

• C-9, as hydroxylation at both sites is common to all of the (iso)nanangenines. The 9-hydroxylation also results in migration of the double bond on the decalin to Δ7,8. The two hydroxylations could be catalysed by the FAD-dependent oxidoreductase or one of the cytochrome P450 oxygenases. From this

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

• lead to different migration of the double bound and different hydroxylation pattern (Table 2 and Scheme 1). An exchange to leucine drastically changes the product to cembrane A (7) and 3,7,18-dolabellatriene 12 (Table 2 and Scheme 1) [36]. The cation migrates via a 1,5 hydride shift, as shown by

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• /dehydration process in the side chain), treatment with conc. aqueous hydrochloric acid gave a complex, bridged molecule under C–C-bond formation of the lactone moiety with the pyrrole, migration of the isopropyl group and loss of the carboxanilide residue. The novel degradation products were characterized by

• product 7. Proposed mechanism for the formation of bridged product 6 under cyclization, isopropyl migration and carboxanilide fragmentation. Acidic stress conditions and decomposition products formed. Supporting Information Supporting Information File 251: Materials and methods; stress tests and

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• -ring system; palladium-catalyzed carbonylation and in situ lactone formation, and rhodium(II)-catalyzed double bond migration to construct the D-ring; and palladium-catalyzed Csp2–H oxygenation to install the C-14 hydroxy group. In 2016, Qin and co-workers developed a catalytic asymmetric route toward

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• along with 8% of the alkene 22. It is proposed (Scheme 5) that these products arise from stepwise formation of the cyclopropylcarbinyl cation 23. This cation can rearrange via migration of bond a to give the cyclobutyl cation 24. The cis-nature of the phenyl group and the hydrogen in cation 23

• necessarily results in the formation of the γ-silyl-stabilized cation 24. This cation is the source of the acetate 21. Alternatively, cation 23 can rearrange by migration of the b bond of the cyclopropane. This leads to the β-silylcyclobutyl cation 25, which can subsequently desilylate to give the minor

• cyclopropylcarbinyl cation 26 rearranges by migration of the a bond of the cyclopropane to give the cyclobutyl cation 27. This cation 27 is different from the γ-silyl-stabilized cation 24 in that the cis-nature of the phenyl and TMS groups in 26 requires that these groups are closer to each other in 27. Shown in

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• studies of tri-, tetra-, and pentacationic systems [11][12]. This product, 10, is the result of charge migration involving the carbocation center and the phenyl group (vide infra). When compound 9 is treated with only superacid, the bis(pyrido[1,2-a]indole) 11 is formed as the major product. Likewise, the

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• avoid any silyl migration [12]. As already shown [12][13], n-butyllithium proved to be very efficient, although stronger or complex bases are usually required to produce oxiranyl anions [1][2][24][25][26][27][28]. Upon deprotonation, the corresponding oxiranyllithium was sufficiently stable at −78 °C

• ] transferring the non-oxygenated boron substituent and promoting oxirane ring opening [39]. The group’s migratory aptitude cannot be directly compared to that known from cationic rearrangements, because the nature of the other boron substituents plays a key role in migration, as revealed by calculations [40][41

• B could be envisaged with the large pinacol substituent facing the small oxirane ring and thus placing the migrating group antiparallel to the adjacent oxiranyl C–O bond. This may explain the role of the diol substituent on the reaction efficacy (see Table 1). Upon migration and oxirane ring opening

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• sulfonylacrylamide 123 (Scheme 36). Then, ipso-cyclization of radical 125 to 126, departure of SO2 and final oxidation of 127 by Cu(II) would provide oxindole 124. As a consequence of this desulfonylative 1,4-aryl migration, the SO2 group initially present in the starting acrylamide is replaced by another SO2 moiety

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• spectra from the incubations of HcS with (1R)- and (1S)-(1-13C,1-2H)FPP, resulting in a singlet for the (R)-case and a triplet in the (S)-case indicating a direct C–D bond, clearly demonstrated the stereospecific migration of HR from C-1. To complete the observations also for C-10, (2-13C)DMAPP was

• catalysis suffers from poor selectivity. Nevertheless, the formation of multiple sesquiterpene products demands for a challenging mechanistic model, which was refined by extensive labelling experiments. Several interesting details were disclosed including the stereochemical course of a 1,3-hydride migration

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

• ). However, purification of 4a by column chromatography on SiO2 favored acyl migration in 4a, thereby dropping the yield of 4a by increasing the amount of the isomeric sn-2,3-protected monoacylglycerol 4a’ (Figure 2) [42]. Typically, cobalt complex (S,S)-cat has been used for kinetic resolution of racemic

• by an aqueous work-up gave DAG 6a in only 31% yield, together with concomitant acyl migration of the corresponding sn-1,2-diacylglycerol 6a into sn-1,3-diacylglycerol 6a’. Therefore, the desilylation reaction was carried out by stirring 5a and BF3·CH3CN (Scheme 5a). Next, DAG 6a was reacted with 4

• through acyl migration of 6a under the basic milling conditions. Subsequently, the reaction mixture containing 8a and 8a’ was milled with 7-hydroxycoumarin (9) and triethylamine to achieve the conjugation of the DAGs 8 in 53% yield after two steps (Scheme 5c). A mixture of 10a and 10a’ (10a/10a’ 72:28

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• of the C-2,C-3-double bond by the enzyme’s active site (e.g., on top of it, Figure 4A). This migration of OPP to C-3 results in a reorganisation of the resulting structure to a cisoid conformation for the follow up 1,6-ring closure. To explain the astonishing selectivity between the two NPP

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• neurotransmitters to appear during development [11] and may have an organizing function in the development of the mammalian CNS being involved in cell division, differentiation, survival, neuronal migration [12][13] and synaptogenesis [14]. Dysfunction of the 5-HT receptor (5-HTR) signalling during early

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• % yield (1:1 mixture of the two possible diastereomers). Probably due to the bulkiness of the acyl group, the migration to the nitrogen is strongly hampered and hence the three-component cascade almost completely stops at the stage of aminobutadiene C (see Scheme 2) that is hydrolyzed during work-up to

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• reactants. In the reaction of monovinyl-POSS with allylbenzene, CM was accompanied by double bond migration, which results in reduction of the isolated yield of the CM product (85%) and the formation of minor amounts (15%) of 1-propenylbenzene. No similar isomerization was observed in the reaction of POSS

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

• elimination and thus interrupts the catalytic cycle. For these reasons we started from the MOM-protected 8-allylcoumarins 7, which underwent the Ru-hydride catalyzed double bond migration smoothly. The MOM group was cleaved off without isolation of the intermediate products and the required 7-hydroxy-8-(prop

• . Starting point was the 7-acetamido-substituted coumarin 18 [29], which was first N-allylated to the allylamide 19. Dual double bond migration was accomplished with the Ru–hydride complex used previously and furnished the enamide 20 in high yield and predominantly as the E,E-isomer. In light of previous

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• problem during its preparation occurred, i.e., benzylation of the axial 4-OH only gave the desired 4-O-Bn product as a minor product, whereas the benzoyl migration from the 3-O to the 4-O, followed by benzylation of the 3-O, was the major, if not the exclusive, product. Despite several different

• the 6-O-TBDPS protection the Latrell–Dax inversion provided slightly higher yields of 1, whereas with the 6-O-Bn 8, the two methods provided comparable yields. Migration of the benzoyl group under the 4-O inversion conditions was irrelevant as it is removed in the following step. The proposed

• and faster access to these biologically abundant and relevant α-D-GalpNAc-(1-3)-D-GalpNAc motifs. Undesired migration followed by benzylation of the 3-O-Bz GalN3 using several different benzylation procedures (LG: leaving group). Simple synthesis of two acceptors and two donors from the same common

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• -(phenylthio)propyl)-N-((4-(hydroxymethyl)-1-tosyl-1H-pyrrol-3-yl)methyl)-4-methylbenzenesulfonamide (9a) was apparently obtained via the sulfanyl group migration (S-shift reaction) (refer the NMR studies of 9a in Supporting Information File 1). To clarify the details of the S-shift reactions, we performed the

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• opening of the heteroring, (Scheme 7). The process involves isomerization through olefin bond migration proceeding Z-selectively. Conclusion The ring-opening metathesis (ROM) of some ring-constrained, unsaturated bicyclic frameworks has been studied in the presence of commercially available ruthenium

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• cells treated with P. aeruginosa quorum-sensing (QS) molecules, in order to elucidate their role in the occurrence of tissue damages, in which endothelial cells are involved, such as: wound healing, transepithelial migration of neutrophils, lung inflammation and permeability. Also, we highlighted the

• increased expression by 9 and 11 fold, respectively, was obtained when endothelial cells were treated with C4HSL (Figure 5). Migration of leukocytes from vessels into infected tissues involves interaction with endothelium through adhesion molecules. Adhesion molecules such as integrins (Cd11/Cd18) and ICAMs

• are usually involved in the inflammatory process during infection. P. aeruginosa-activated mast cells produce IL-1α and IL-1β, which stimulate the expression of ICAM-1 and E-selectin in endothelial cell, this process being required for transendothelial migration [23]. Furthermore Lins et al. showed

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• also described, with a focus on radical-involved reactions in terms of organic synthesis. Keywords: dehalogenation; electrolysis; green chemistry; heptamethyl cobyrinate; methyl transfer; 1,2-migration; photosensitizer; vitamin B12; Review 1. Introduction 1-1. Redox and coordination chemistry of B12

• catalytic reactions We deeply investigated the electrochemical catalytic reactions mediated by 1 and related complexes and succeeded in the functional simulations of MMCM-type 1,2-migration reactions [42]. For example, when 2,2-bis(ethoxycarbonyl)-1-bromopropane was selected as a model substrate, the 1,2

• -migration of carboylic ester (80%) and some simple reduction product (20%) were obtained under controlled-potential electrolysis at −2.0 V vs SCE in the presence of catalyst 1 in DMF (Scheme 1b) [54]. There were different ratios for the simple reduced product and the ester-migrated product, depending on the

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• -targeting by application of a GnRH analog as a carrier to deliver a covalently linked chemotherapeutic drug directly to the tumor cells. In this study our aim was (i) to analyze the effects of GnRH-drug conjugates on melanoma cell proliferation, adhesion and migration, (ii) to study the mechanisms of tumor

• effect of a drug-containing GnRH conjugate (AN-207) clearly indicated that GnRH-R receptors are suitable for targeted tumor therapy [24][26]. Besides the well-established antitumor activity of GnRH variants (e.g., goserelin), their negative effects on tumor cell migration and invasion have been also

• activity but also modulatory effects on cell adhesion and migration of melanoma cells. In our present work the effects of 3 Dau-GnRH-III conjugates – those carrying 4Lys with acetyl or butyryl side chain a “second drug” ([4Lys(Ac)]-GnRH-III(Dau=Aoa), [4Lys(Bu)]-GnRH-III(Dau=Aoa)) and the parent conjugate

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

• metal occurs, and the alkenylzinc intermediate E is subsequently obtained, along with the regeneration of Co(I) species A (step d). After 1,4-migration of zinc in E, product 19 is obtained (step e). Visible-light-driven hydrocarboxylation of alkynes The Use of photoenergy to organic synthesis is of