Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• analogue with electron-donating substituents, illustrating that the insecticidal activities of spinetoram J analogues are closely related to the electrical properties of the substituents. For compound 7c, the methoxy group was attached to the benzene ring at the meta-position, leading to a decrease in the

• conjugate effect, mainly for the role of electron absorption. So the compound 7c exhibited much more efficient insecticidal activity than the C17–O-benzyl analogues with electron-donating substituents. Therefore, an electron-donating substituent is more likely to generate a promising analogue with good

• with Na2SO4 and evaporated under reduced pressure. The residue can be used directly in the next reaction step. Preparation of spinetoram J analogue 4 Compound 2 (0.32 g, 0.79 mmol) and compound 3 (0.68 g, 1.87 mmol) were dissolved in 10 mL dry CH2Cl2 with some molecular sieve under Ar. Then BF3·(C2H5

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• ) substituents in the aromatic ring (products 3ca, 3da, 3fa, 3ha, 3cb–hb, yield 34–91%), and an electron-donating methyl group (products 3ba, 3ea, 3ga, 3bb, yield 39–85%). Good yields (60–79%) were achieved with a cyclic analogue of styrene – indene (1k, compounds 3ka, 3kb). β-Substituted styrenes (β-methyl

Synthesis and supramolecular self-assembly of glutamic acid-based squaramides

• Juan V. Alegre-Requena,
• Marleen Häring,
• Isaac G. Sonsona,
• Alex Abramov,
• Eugenia Marqués-López,
• Raquel P. Herrera and
• David Díaz Díaz

Beilstein J. Org. Chem. 2018, 14, 2065–2073, doi:10.3762/bjoc.14.180

• concentrations and gel-to-sol transition temperatures were also determined for each case. In addition, the superior squaramide diester gelator was compared with an analogue triazole-based gelator in terms of critical gelation concentration, gelation kinetics and thermal phase transition. Keywords: glutamic acid

• properties of the gels obtained with these compounds. In general, compound 2 formed gels in more solvents, at lower concentration and faster than compound 1. In this work, and based on our previous experience with organogels based on squaramides [21], we decided to prepare and study an analogue of N-stearoyl

• due to the delicate equilibrium between metastable gel and thermodynamically stable crystalline phases [39][40]. Squaramide 3 formed stable gels in the same number of solvents than the analogue triazole-based gelator 2, which was previously found to be superior to the amide 1 [33]. Similarly to 3, CGC

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• backbone of complex 16·Ni2(OAc)2 shows a helical arrangement. This helicity is facilitated by the innate stereogenic centers of the oxazoline moieties which is further extended by the flexibility afforded by the amide connections. Naphthyridine ligand 22-H2 was designed as an analogue of ligand 16-H2 that

Synthesis and characterization of π–extended “earring” subporphyrins

• Haiyan Guan,
• Mingbo Zhou,
• Bangshao Yin,
• Ling Xu and
• Jianxin Song

Beilstein J. Org. Chem. 2018, 14, 1956–1960, doi:10.3762/bjoc.14.170

• 1400 nm with several observable peaks. This remarkable absorption in the NIR region is comparable with that of the analogue “earring” porphyrins and reveals the π-conjugation between the subporphyrin and tripyrrin moiety. Conclusion In summary, we synthesized a π-extended “earring” subporphyrin from β

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• spirocyclic glycoside that was launched as antidiabetic agent in 2012 in Japan [15]. Rolapitant (5) is a marketed drug that was approved in 2015 for the treatment of nausea and vomiting [16]. Compound 6 is a spiropyrimidinetrione analogue which is currently in clinical trials for the treatment of gonorrhea

• I (30) to its spirocyclic analogue arnottin II (32) by reaction with LiOH followed by PIFA (31). The spirocyclic product arnottin II (32) was isolated in 56% yield (Scheme 7). This approach is based on a tandem oxidative dearomatization process and will be quite useful for the conversion of

• )-mediated spirocyclization of aryl alkynes 24 to spirolactones 26 by the reaction with bis(iodoarene) 25 in the presence of mCPBA. Bridged iodine(III)-mediated spirocyclization of phenols 27 to spirodienones 29. Iodine(III)-mediated spirocyclization of arnottin I (30) to its spirocyclic analogue arnottin II

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• , t = triplet, q = quartet, br = broad, m = massif, mult = multiplet). 2D NMR spectra (COSY, HSQC, HMBC, HSQC) were recorded to complete signal assignments. Melting points were recorded on a Stuart Scientific Analogue SMP11 or Büchi Melting Point B-545. Infrared spectra were recorded on a Bruker Alpha

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• comportment of G-1 piperazine dendron D-N

  NH being not entirely ruled out [68]. In line with this hypothesis, we recently described [35] the aptitude of the non-O-n-octylated analogue of G-2 dendrimer 4 (Scheme 3) to deprotonate Hemin completely (1:5 molar ratio), thus generating a new MOF for H2O2

• direction to the other five, caused, probably, by the propeller orientation (Figure 1) of the three covalent junctions around the benzene core. In contrast, the energetic minimum of the ionic analogue 7b could be accessed in a gradual approach only. Thus, we had to start from a preliminary DFT calculation

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

• -chloroacetyl-D-glucose (30) as well as its galacto-configured analogue with the carboxylic acids 31–34 to obtain products 35–38 which are related to various pesticide agents (Scheme 6). Their results supported the theory that, along with an effect of the reaction temperature, an increase of the pKa of the

• synthesis of various jadomycins [54]. Whereas the Mitsunobu glycosidation of 68 with the phenolic aglycon 70 yields the pure 1,2-trans-glycoside 71, the 2-deoxy sugar 69 yields the glycoside 72 as a 6:1 α,β-anomeric mixture (Scheme 11). In contrast to this, the jadomycin B carbasugar analogue 75 was formed

• Mitsunobu methodology, the rebeccamycin analogue 124 was synthesized in high yield and complete β-stereoselectivity by Wang et al. from the glucose derivative 2 and 123 (Scheme 25) [101]. Application of the anomeric Mitsunobu coupling in nucleoside synthesis was pioneered by Szarek et al. [102], who reacted

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• Information File 2, Table S2a and b). The GnRH-III analogue of AN-152, GnRH-III(Dox-O-glut) (1) showed comparable antitumor effect with that of AN-152 [14]. Results of our study indicate that conjugate 1 had similar cytotoxic effect as doxorubicin and AN-152 on endothelial cells at the two highest

Steric “attraction”: not by dispersion alone

• Ganna Gryn’ova and
• Clémence Corminboeuf

Beilstein J. Org. Chem. 2018, 14, 1482–1490, doi:10.3762/bjoc.14.125

• stabilizing extremely crowded systems, hexaphenylethane (3) being the mascot of this concept. As elegantly illustrated by Schreiner and Grimme [3][4], while bare hexaphenylethane (3) is thermodynamically unstable due to significant Pauli repulsion between the phenyl rings, its analogue 4 carrying all-meta

• representative class (II) and class (III) systems: tetracene (7) and its fully saturated analogue, perhydrotetracene (10, Figure 5A and B). For each monomer, four types of dimers were compared – perfectly stacked (i.e., the frozen dimer) and shifted transversally, laterally and in both directions by approx. half

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• of the achiral calixarene platform, the monomeric analogue carrying both thiourea and primary amine subunits was also prepared and used in the control experiments. Under optimal reaction conditions, the noncyclic analogue afforded the product in lower yields and enantioselectivities (52% yield, 89

• analogue 68 bearing the same bifunctional pattern was also prepared from p-tert-butylphenol and used for comparison (Scheme 19). When monomeric analog 68 was used as a catalyst alone or in the presence of p-tert-butylphenol/phenol as acidic additives, lower yield and enantioselectivity were observed. These

• converted to the the carboxylic acid analogue 82 by treatment with sodium hydroxide in MeOH at ambient temperature. Finally, deprotection of Boc groups under standard conditions afforded the targeted organocatalyst 83. Magnetic nanoparticles (MNPs) due to their high surface area have been widely used as

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• 24 h) and the isolated yields are often close to 90% for the ordinary substituents (alkyls, aryls, halogens) of the sydnone. Somewhat lower yields were obtained in ethyleneglycol [5]. The reaction of the parent 1-phenylsydnone with DMAD and its diethyl analogue has also been performed in

• supercritical carbon dioxide [41] in which 65 and 83% yields of dimethyl (or diethyl) 1-phenylpyrazole-3,4-dicarboxylates were achieved. Only in two cases involving 3-(2,4,6-trisubstituted phenyl)-4-iodosydnones (R1: 2-Br-4,6-diMe-Ph, 2,4-diBr-6-Me-Ph; R2: I) and DMAD (or its diethyl analogue) did the

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• of a mixture of 18 with DNA-APoly in thermal melting studies, as compared to the non-hybridized, single-stranded oligonucleotides [41]. This indicated a successful complex formation with ordered base stacking of the positively charged oligonucleotide analogue and its native DNA counterstrand. When

• review. Fathi et al. have established the aminoethylphosphonate linkage 19 (i.e., a phosphonate analogue of amidate 7) [47], and Rahman, Obika and co-workers have described cationic phosphorothioates of type 20 [48] (Figure 4). The preparation of phosphonate linkage 19 was achieved in diastereomerically

• the cleavage conditions used in the solid phase-supported synthesis of native DNA and also allowed the introduction not only of pyrimidine, but also of purine bases into the oligonucleotide analogue [53]. The method was based on the activation of the 5′-monomethoxytrityl (MMTr)-protected 3'-thiourea

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• cryptophycin analogues. The O-methyl group of the unit B D-tyrosine analogue was replaced by an O-(allyloxyethyl) moiety, an O-(hydroxyethyl) group, or an O-(((azidoethoxy)ethoxy)ethoyxethyl) substituent. While the former two maintain cytotoxicity in the subnanomolar range, the attachment of the triethylene

• analogue of cryptophycin-1 (Figure 1). Eli Lilly took cryptophycin-52 into clinical trials. Although almost half of the patients obtained a benefit from the treatment, neurotoxic side effects forced the termination of the clinical trials [21][22][23]. In order to overcome the side effects of cryptophycin

• column chromatography. The allyl ether in 23 was cleaved using Pd(PPh3)4 as Pd(0) source and phenylsilane as scavenger to obtain the cryptophycin analogue 24 in good purity. Biological evaluation The biological activity of the modified unit B analogues was determined in a cell viability assay using the

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• dimethyl malonate and its nitro analogue gave benzoheptafulvalene derivatives 52 and 53 [50][63]. The condensation of 4,5-benzotropone (11) and anthrone (10H-anthracen-9-one) also afforded 4,5-benzo-tropyliden-anthron 54 in 65% yield [63]. Kitahara reported the synthesis of 1,2,3,4-tetrachloro-7,8

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• which contains a free phenol moiety, were also tolerated (69% and 65% yield, respectively), as was the highly deactivated pentafluorophenyl analogue 2j (48%). To briefly explore the effect of chain length on efficiency, the cyclisation of N-(but-3-en-1-yl)benzamide and N-(pent-4-en-1-yl)benzamide was

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• -fluorouracil (5FU) and nucleoside analogue prodrugs subject to mechanochemical co-crystal or polymorph transformation. Nucleoside tritylation effected by hand grinding in a heated mortar and pestle. Persilylation of ribonucleoside hydroxy groups (and in situ acylation of cytidine) in a MBM. Nucleoside amine

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• /β-CD inclusion complex. Phenoxodiol is an isoflavone analogue that possesses potent anticancer properties. The asymmetric unit of phenoxodiol/β-CD includes one guest molecule encapsulated by two β-CD molecules, and twenty-six water molecules. All the water molecules surround the external area of the

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

• , C2'-substituted ribonolactones were employed in the synthesis of 2'-β-Me analogues 7 and 8 and the 2'-deoxy-2'-fluoro 9 (Figure 7B) [65]. The 1'-α-H analogue 2 was reported to exhibit inhibitory activity against neoplastic cell lines [86]. This scaffold was later elaborated by Gilead to discover

• ) increases the loading of macrophages derived from human monocytes over its unmasked analogue [64]. It was also observed that intravenous administration of the prodrug leads to increased liver loading (as the triphosphate) in hamsters compared to oral dosing [63]. Draffan et al. synthesized a series of 2'-β

• hydrogenation afforded the optically pure carbocyclic tubercidine analogue (−)-53. This compound has shown potent activity against breast cancer cell lines and human foreskin fibroblasts [53]. Conclusion With increasing reports of emerging and reemerging infectious diseases globally, there is a need to develop

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• of the human GnRH-I, the sea lamprey analogue GnRH-III (

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• reaction to afford the desired alkenylation product 3aa albeit in moderate yields (Table 1, entries 3 and 4). No significant improvement was observed using the saturated analogues of IMes·HCl and IPr·HCl (Table 1, entries 5 and 6) or the 2,6-diethylphenyl analogue (IEt·HCl, Table 1, entry 7). Furthermore

• reaction (Table 1, entry 8). To our delight, we observed a remarkable improvement in the reaction efficiency using the benzofused analogue of IPr·HCl (L2·HCl), affording 3aa in 88% yield without any trace of a dialkenylation product (Table 1, entry 9). It should be noted that, unlike the C–H arylation of

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• provide 3-substituted isoindolinones in good yields and diastereomeric excesses. This methodology was applied to the asymmetric synthesis of a new pazinaclone analogue which is of interest in the field of benzodiazepine-receptor agonists. Keywords: asymmetric organocatalysis; Aza-Michael reaction; phase

• X-ray analysis of a single crystal allowed us to assert the (2R,3S) configuration of 3a (Figure 5). This result allowed for the determination of the absolute configurations of all isolated isoindolinones. Asymmetric synthesis of a new pazinaclone analogue With this handful methodology in hands, we

• then turned our attention to the asymmetric synthesis of a new pazinaclone analogue, which could be of particular interest in the field of benzodiazepine-receptor agonists [8][9][10][11][12][13][14][15][16][17]. Indeed, pazinaclone produces its sedative and anxiolytic effects by acting as a partial

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• ]. With these issues in mind, we carried out a retrosynthetic analysis (Scheme 2) in which 10, an iodo analogue to the starting material 3, could be generated in a single step via a decarboxylative ring-opening of α-acetyl butyrolactone 8. The iodo analogue 10 could then be used without isolation to

• ). Results and Discussion Initial optimization efforts to prepare 6 (Scheme 1) revealed poor reactivity of starting material 3, so we pursued the iodo analogue of 3, 5-iodopentan-2-one (10) as an alternative. By optimizing the reaction concentration, we have also shown that (see Table S1 in Supporting

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• -position to the sulfur atom. Under the conditions, a camphor-substituted analogue was anodically fluorinated with moderate diastereoselectivity. Moreover, the anodic fluorination of a cyclic benzothioate such as benzothiophenone was also successfully demonstrated. In contrast, the anodic fluorination of S