Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• (Scheme 36) [53]. CHCl3 was proved to be a superior solvent for the MBH reactions. Most of the products were obtained in excellent yields and with excelent enantioselectivity, for N-unprotected maleimide, the corresponding product was obtained in a lower yield and enantioselectivity (75% yield and 77% ee

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• sorting, in photodynamic therapy and in colorimetric enzymatic tests (ELISA). Although it is possible to modify xanthene dyes with specific functional groups (e.g., isothiocyanates, maleimide, succinimidyl), enabling them to react with amine groups, such chemical modifications dramatically affect the cost

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• loading. The authors proposed a bifunctional mode of activation. More specifically, the thiourea moiety activates the maleimide through hydrogen-bonding and the tertiary amine recognizes the thiol group, again through hydrogen-bonding, and orients the thiol attacking from the Si-face of the maleimides 52

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee). Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized. Keywords: 7-azaisatins; β-isocupreidine; bifunctional catalysis; maleimide; MBH

• enantiocontrol was diminished at 70 °C (Table 1, entry 10). On the other hand, when α-isocupreine (α-IC) [24][25] was employed as the catalyst instead of β-ICD, unfortunately no desired product was obtained even after 120 h (Table 1, entry 11). Finally, we compared the reaction of 7-azaisatin 1a and maleimide 2a

• , entries 2–4) while good results were obtained in a mixture of THF and DCM for a maleimide with an electron-deficient N-aryl group because of better solubility (Table 2, entry 5). In addition, N-alkylated maleimides provided the desired products in good yields (Table 2, entries 6–9), while only moderate

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• intermediate 15 under Zémplen conditions, i.e., catalytic NaOMe in MeOH [40], safely afforded the target conjugate 16 in 84% yield without affecting the DMM group. Despite, the two C=O groups could not be seen with certain at δ ≈ 174.00 ppm (13C NMR), the two maleimide CH3 groups were observed at δ = 8.80 ppm

• . The C=O signal (13C NMR) was observed at δ = 183.10 ppm with concurrent disappearance of the maleimide CH3 signal. A peak was observed at m/z value corresponding to the exact molecular mass. Conjugate 20 was prepared under similar conditions as employed for the synthesis of compound 17. Thus, coupling

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• substituents. The P25 SCPC reactions of aryloxyacetic acids with maleic anhydride or maleimide substrates gave the expected adducts 29 but also launched an alternative reaction channel resulting in novel chromenedione derivatives 31 (Y = O, NR). These are evidently formed when the initial adduct radicals 27

• cyclized onto the aryl rings 30 followed by rearomatization (Scheme 7). Good to excellent overall yields were obtained under all conditions. Excess maleic anhydride or maleimide was necessary as the sacrificial electron sink; hence moderate amounts of succinic anhydride or succinimides were byproducts. The

• -Bu, MeS or di- and tri-MeO), underwent addition–cyclization reactions with maleimide on UVA irradiation, but in the complete absence of photoredox catalysts [63]. Good to excellent yields of chromenopyrrolediones and pyrroloquinolinediones (32, X = O, NR) were obtained from photolyses in H2O/MeCN

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

• -pentyne and NaH in DMF to deliver compound 287. Then, indole-3-glyoxylate 288 was converted to N-alkylated derivative 289 by the treatment with 5-chloro-1-pentyne in the presence of cesium carbonate. The maleimide condensation of 287 and 289 was carried out in the presence of KOt-Bu at 0–23 °C to give the

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• important monomers for the synthesis of polymers used in high temperature applications [61][62][63]. Methyl maleic anhydride and p-bromoaniline smoothly provided the corresponding maleimide (Table 3, entry 5). The reaction of p-toluidine and phthalic anhydride was very facile and the corresponding

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• ) was selected and synthesized on Rink amide polystyrene resin. For attachment to the polymer carriers the N-cysteinylated peptide CGPPPRGPPPR-NH2 (P2) was prepared, containing a free N-terminus in order to enable the attachment to polymers via native chemical ligation or Michael addition to maleimide

• maleimido groups by reaction with N-3-chloropropyl maleimide for ligand attachment. Finally, dextran, a polysaccharide containing α-1,6-linked D-glucose as repeating unit, was selected as the second linear carrier. The D-glucose units in the polysaccharide are fixed in the 1C4 chair conformation and thus

• ) was further converted by condensation with 2-N-maleimido-ethylamine and N-ethyl-N´-dimethylaminopropylcarbodiimide (EDC) [6]. The monovalent ligand peptide 2 was attached to the dextran carriers by nucleophilic addition of the thiols to the maleimide double bond furnishing peptide–polymer conjugates

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• and BMP-2s are integrated in matrix metalloproteinase (MMP)-degradable PEG-maleimide hydrogels. The peptide ligands successfully host stem cells in vivo, and the sustained release of low doses of BMP-2 direct endogenous stem cell differentiation and promote bone healing [87]. Furthermore, the signal

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• by Seitz and co-workers using thiols imbedded in the backbone of the PNA that were chemoselectively conjugated to a maleimide–glycan adduct [43]. Our first efforts in the area of glycan display aimed to demonstrate that a DNA template could be used to program the assembly of discrete PNA-tagged

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• including azide–alkyne cycloadditions [9][10], Diels–Alder reactions [11][12], maleimide–thiol reactions [13], thiol–ene additions [14], and imine/oxime conjugations [15]. In this article we demonstrate that dihalocarbenes can be used to generate dihalocyclopropanes on olefin terminated SAMs. We recently

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• rationalized using semi-empirical calculations. In the same contribution, the cascade reactions starting from uracil polyoxin C 106 were described (Scheme 44). Decarboxylative formation of azomethine ylides from 106 and an aldehyde (or ketone), followed by reaction of the ylide with maleimide afforded mixtures

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• Scheme 3 [34]. Analysis of the PEGylated species showed more than 90% conversion, whereas less than 30% of the protein was PEGylated by direct conjugation of the albumin with commercial PEG-maleimide. The PEG-Hz may undergo pH controlled hydrolysis which also depends on the number of units in the linked

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• -terminated SAMs [33], by Diels–Alder reaction of cyclopentadienes and furans on maleimide-terminated SAMs [34], by thiol–ene click reaction of functionalized thiols on alkene-terminated SAMs [35] as well as by strain promoted cycloadditions on azide- and nitriloxide-terminated SAMs [36] using μCP. Homogenous

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• maleimide derivatives. Our preference for this dienophile was dictated by a recent patent on the lifespan altering properties of cycloadducts involving maleimide dienophiles [20]. Moreover, very recently we have characterized some furo[3,2-h]quinoliniums as potent non-detergent spermicides [19], which

• /antifungal/spermicidal/lifespan altering agents, where furo[3,2-h]quinoliniums were employed as dipole precursors and maleimide derivatives as dipolarophiles. We initially employed the protocols from our recently developed green methodologies [21][22][23][24][25], which however failed to give any promising

• cycloaddition is presented in Scheme 3. The base (DBU) abstracts the acidic proton of furo[3,2-h]quinolinium 9a to generate the 1,3-dipole I. The Cu(II)–phenanthroline system activates the maleimide dipolarophile via coordination with the carbonyl group to undergo a [3 + 2] cycloaddition with the 1,3-dipole to

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

• and only two examples of MC approaches have been included in the manuscript. The reported examples involve (hetero)aryl aldehydes 77, methyl glycinate (78) and maleimide 79 or (E)-1,2-bis(phenylsulfonyl)ethylene (80) as electrophilic alkenes. The reported work is an extension of a previous paper

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• by using a chiral auxiliary (>95% de in the case of an L-proline-derived diene). Diversification on the different units, diene, dienophile and aldehyde, has been described. Concerning the maleimide material, substituent R3 did not exert any significant effect on the process. Other dienophiles have

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• to trap the dipolar intermediate 11 with N-methylmaleimide [25]. However, from the reaction mixture of thioketone 1a, diazoacetylacetone 2a and maleimide (as an intercepting agent) solely 1,3-oxathiole 3a was isolated in 40% (68%) yield. In the 1H NMR spectrum of the crude reaction mixture no

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• -bromophenyl)maleimide a good enantioselection was observed when the reaction was run at −20 °C furnishing enantiomerically pure 7af in good chemical yields (Table 2, entries 9 and 10). The variation of the arene substituent of the azlactones promoted also excellent to good enantioselections in compounds 7ba

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• starting from tert-butylamidoxime and 4-aminobenzoic acid or 4-nitrobenzonitrile. The structures of compounds 1, 2, 4, 5 and 6 were confirmed by X-ray crystallography. Keywords: antitumor activity; bioisosteres; maleimide; natural product analogs; 1,2,4-oxadiazoles; Introduction The five-membered

• antirhinovirals [11], benzodiazepine receptor partial agonists [12], anti-inflammatory [13], muscarinic agonists [14], serotoninergic (5-HT3) antagonists [15], and growth hormone secretagogues [16]. The maleimide motif is also a useful five-membered heterocycle in pharmacological chemistry. Kratz et al

• . synthesized maleimide derivatives of doxorubicin and camptothecin. After intravenous administration these designed anticancer drugs bind rapidly to circulating albumin [17][18][19]. Endogenous albumin could be seen as a drug carrier, as it accumulates in solid tumors according to the pathophysiology of tumor

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• quantities of materials without the need for particularly specialist equipment. By using an inexpensive peristaltic pump, the [2 + 2] cycloaddition of maleimide (76) and n-hexyne was run continuously for 24 hours under optimised conditions for a custom-built Pyrex reactor (Scheme 25). This reaction produced

• productivity of the Vycor reactor illustrates the importance of glassware choice for UV transmission. The N-pentenyl substituted dimethyl maleimide 78 underwent a [5 + 2] photocycloaddition to the corresponding azepine 79 with a productivity of 39 mmol/h. The same reactor was also used to optimise the [5 + 2

• achieved by immersing the FEP-wrapped well in a methanol-containing cooling bath. At a given temperature the d.e. of the products 90/91 under flow conditions was superior to that when carried out as a batch process. Flow conditions were employed by Seeberger et al. in the [2 + 2] cycloaddition of maleimide

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

• nortopsentins [21][22][23]), dihydroimidazole (discodermindole [24]), oxadiazine (alboinon [25]), piperazine (dragmacidon [26]), maleimide (didemidines [25]), and pyrimidine (meridianins) [27][28][29]. Among these, meridianins (Figure 1), the tethered biheterocycles isolated from the south Atlantic tunicate

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• ; maleimide; organocatalysis; parallel synthesis; reductive amination; Introduction In recent years, the rapid access to structurally diverse and complex small molecules has grown in importance within the context of high-throughput screening of biologically relevant targets. The need for such compounds, both

• the maleimide component in Scheme 2. Consequently, higher diastereoselectivity was required for the synthesis of enantioenriched γ-lactams. Indeed, 3{1,1} could be produced with moderate diastereoselectivity when the reaction was performed at 0 °C over a prolonged length of time (Table 1, entry 11

• TOF spectrometer for electrospray ionization (ESI). General procedure for the asymmetric organocatalyzed Michael addition of aldehyde 2{1} to maleimide 1{1} to produce 3{1,1} (Table 1) Propionaldehyde (2{1}) (31.2 μL, 0.433 mmol, 1.5 equiv) was added to a solution of N-phenylmaleimide (1{1}) (50.0 mg

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• % ee. The nonsubstituted benzoylacetate 1e gave product 2e in good yield 69% but low ee (31%). Ethyl 2-cyclohexanonecarboxylate (1f) afforded product 2f in 73% yield and 63% ee. Reactions of ethyl benzoylacetates with bigger substitution groups, such as phenylsulfonyl and maleimide derivatives, were