Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• activation with cycles of violet and green light. Due to the very long-lived metastable cis configuration, 4FAB in vivo use could be of great promise for long term biological studies. Further chemical functionalization of this 4FAB probe with a maleimide functionality allowed clean cross-linking with

• temperature. The maleimide-substituted compound 1 reacted with the cysteine of glutathione, however, we found that this "4FAB version" of MAHoCh (Scheme 1) did not enable significant perturbation of nicotinic acetylcholine receptor currents used with MAHoCh [16]. However, when 4FABTA analog 2 was tested as a

• maintains the near-ideal chemical properties of Hecht’s 4FAB chromophores [12][13] (see below). The final synthetic challenge was the installation of a maleimide onto chromophore 2. The original AB photoswitchable probes which were cross-linked to cysteine mutants had amides with a reverse orientation [19

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• Valentina A. Ol'shevskaya Elena G. Kononova Andrei V. Zaitsev A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, 119991, Vavilova St. 28, Moscow, Russian Federation 10.3762/bjoc.15.263 Abstract Maleimide-containing fluorinated porphyrins and chlorins were

• prepared based on the reaction of Zn(II) or Ni(II) complexes of 5,10,15,20-tetrakis(4-amino-2,3,5,6-tetrafluorophenyl)porphyrin and chlorin with maleic anhydride. Porphyrin maleimide derivatives were also prepared by the reaction of 5,10,15,20-tetrakis(4-azido-2,3,5,6-tetrafluorophenyl)porphyrinato Zn(II

• ) or Ni(II) with N-propargylmaleimide via the CuAAC click reaction to afford fluorinated porphyrin–triazole–maleimide conjugates. New maleimide derivatives were isolated in reasonable yields and identified by UV–vis, 1H NMR, 19F NMR spectroscopy and mass-spectrometry. Keywords: chlorin; maleimide

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• (i) maleimide derivatives, (ii) dimethyl acetylenedicarboxylate (DMAD) and (iii) p-benzoquinones. Generic schemes showing pentafulvenes participating as dienophiles in Diels–Alder cycloadditions with (i) o-benzoquinones and (ii) polyhalogenated cyclopentadienes. Reaction of 8,8-dicyanoheptafulvene

Mechanochemical Friedel–Crafts acylations

• Mateja Đud,
• Anamarija Briš,
• Iva Jušinski,
• Davor Gracin and
• Davor Margetić

Beilstein J. Org. Chem. 2019, 15, 1313–1320, doi:10.3762/bjoc.15.130

• mixture of 19 and 18 (3:2 ratio), accompanied with a small amount of 22. As a substitute for dianthracene 19, thermally more stable substrate, anthracene-N-methyl maleimide adduct 25 [54] was prepared by Diels–Alder reaction under high pressure conditions as well as by microwave-assisted reaction and

• mechanochemically (Scheme 5). In this molecule, N-methylmaleimide could be used as protection of the 9,10-positions of anthracene and then removed by FVP. We thought that the maleimide moiety will not be affected in the FC acylation, since the precedencies exist in the literature on imide moiety withstanding the FC

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• be protected as a cyclic acetal instead of the more labile acyclic acetal [5][6]. The maleimide group was incorporated into ODNs as a Diels–Alder adduct with dimethylfuran. Besides the need of an additional step for deprotection, only examples of 5'-end modification was given probably due to the

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• example for an application in biochemistry, Figure 1 shows a compound with cyclooctyne and maleimide as functional units. It was used as a "turn-on" fluorescence probe for cross-linking proteins [13]. The highly reactive cyclooctyne residue undergoes 1,3-dipolar cycloadditions with organoazides (copper

• -free click reactions) [14]. The second functional unit, the maleimide moiety, is a reactive probe for mercaptane, which could be, e.g., a protein holding a cysteine residue on its surface [15][16][17]. The successful ligation by conjugated addition can be followed by the changes of the fluorescence

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• variant of the β-barrel protein FhuA [73][74]. To do so, the authors duplicated multiple β-barrel strands to enlarge the cavity of the protein. HG-type catalysts bearing a maleimide moiety with different spacer lengths (69–71) were covalently anchored to a cysteine of the expanded nitrobindin variant

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• NHC ligand. The conjugation was performed via maleimide-thiol “click” reaction under slightly basic (pH 7.5) conditions. Within the small cavity of NB4, only the GH-type catalyst Ru-6 with the longest spacer was able to undergo conjugation; however, the conjugational yield was very low (25%). Within

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• , the large-scale production and subsequent manipulations of product 4a demonstrated the high synthetic potential of the present MFP method, which is well-suited for the construction of diverse biologically active molecules. a) Light-driven reaction between 2-MBP A and maleimide B for the synthesis of C

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

• ]. In spite of the fact that parent indole is too weak an acid to undergo Mitsunobu conversions, a model maleimide–indole hybrid was investigated by Ohkubo and colleagues to pave the way for the synthesis of indolo[2,3-a]pyrrolo[3,4-c]carbazole compounds with anticancer activity [90][91]. N-Glycosides

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• moderate to good yields (30–79%) and enantioselectivities (70–99% ee). The protocol was compatible to differently substituted isatin imines and maleimide derivatives. In particular, uniformly excellent enantioselectivities (90–99% ee) were achieved in the reaction of N-phenylmaleimide (R3 = Ph) with a

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, China 10.3762/bjoc.14.75 Abstract A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily

• cycloaddition of azomethine ylides with N-alkyl maleimide, followed by a facile oxidation using DDQ as oxidant. Further manipulation with alkylamine/sodium alkoxide alcohol solution conveniently led to novel polysubstituted pyrroles in good to excellent yields (Scheme 1). Results and Discussion As shown in

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• reaction with N-phenyl maleimide, gives rise to formation of S-containing heterocycles by 1,3-dipolar cycloaddition [35]. However, to the best of our knowledge, there are no literature data on analogous intramolecular reactions of C=S ylides involving thiocarbonyl and any other nucleophilic group within

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• that FhuA ΔCVFtev is correctly folded even up to eight weeks. Coupling efficiency of the rhodium catalyst to FhuA ΔCVFtev is more than 90% The rhodium catalyst 1 bearing a maleimide group was attached to FhuA ΔCVFtev for the generation of the biohybrid catalyst [Rh]-FhuA ΔCVFtev 2 as previously

• ]) introduced for maleimide thiol coupling and a high coupling efficiency is achieved (Figure S2, Supporting Information File 1). After coupling, the excess catalyst is removed by washing the protein residue with THF. The dried biohybrid conjugate 2 is dissolved in water and refolded. As refolding reagents, the

• indicate the successful conjugation of the catalyst by an increase of the molecular weight of 116 Da corresponding to the maleimide group (Figure 4). In studies with other catalysts attached to FhuA ΔCVFtev, the addition of water to the maleimide ring was observed [10][47]. During digestion or ionization

Thiazol-4-one derivatives from the reaction of monosubstituted thioureas with maleimides: structures and factors determining the selectivity and tautomeric equilibrium in solution

• Alena S. Pankova,
• Pavel R. Golubev,
• Alexander F. Khlebnikov,
• Alexander Yu. Ivanov and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2016, 12, 2563–2569, doi:10.3762/bjoc.12.251

• for this transformation was postulated. It includes a nucleophilic attack of the thiourea sulfur atom on the C=C bond of the maleimide followed by a proton transfer and nucleophilic attack of the thiourea nitrogen atom on one of the two carbonyl groups; the latter step is considered rate determining

• (Scheme 1). It was reported that the substituent on the maleimide nitrogen atom, particularly a group in the para-position of the phenyl ring in N-arylmaleimides, affects the reactivity of the maleimide toward nucleophilic addition [10]. Strange as it may seem, N-phenylthiourea reacts with N

• solution. As expected, the electronic character of the substituent at the phenyl ring of maleimide 2 (compare 2a, Scheme 2, and 2c,d, Table 1) as well as the size of an alkyl group (compare 3b, Scheme 2, and 3e, Table 1) did not affect the product structure or the tautomeric ratio. A substituent in the

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• , NH 03435, USA 10.3762/bjoc.12.211 Abstract The one-pot [3 + 2] cycloaddition of an azomethine ylide with a maleimide followed by another [3 + 2] cycloaddition of an azide with the second maleimide gives a 1,5-diamino intermediate which is used for a sequential aminomethylation reaction with

• formaldehyde through [5 + 1] annulation to afford a novel polycyclic scaffold bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide in stereoselective fashion. Keywords: [5 + 1] annulation; [3 + 2] cycloaddition; one-pot reactions; stereoselective synthesis

• new sequence initiated with a three-component [3 + 2] cycloaddition for preparing polycyclic scaffold 1 bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide rings. Those heterocyclic fragments could be found in bioactive compounds such as bromodomain, thrombin

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• successfully used as catalysts for anthrone maleimide cycloadditions [29][30][31][32][33][34][35]. In the presence of 10, dichloroanthrone 21 reacted with maleimides 22 and 23 to produce exclusively cycloadducts 26 and 27. In contrast, a mixture of 25 and 28 resulted from the reaction of anthrone 20 and N

• reactions guanidine 10 is not optimal for the preparation of Diels–Alder adducts. We therefore focussed our efforts on the Michael products: Anthrone 20 and maleimide 22 reacted with 0.1 equiv of 10 in THF at −15 °C for 64 h. Chromatographic separation then yielded 51% of 25 and 42% of Michael product 28

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• through the efficient formation of pseudo-intramolecular transition state A. Intermediate B reacted with maleimide 2a to form Cu-pyrrolidine intermediate C. H-HMDS then reacted with the latter to regenerate the chiral CuHMDS and release the product to complete the catalytic cycle. The result obtained by

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• copper(II) complexes were covalently linked to an engineered variant of the transmembrane protein Ferric hydroxamate uptake protein component A (FhuA ΔCVFtev). Copper(I) was incorporated using an N-heterocyclic carbene (NHC) ligand equipped with a maleimide group on the side arm at the imidazole nitrogen

• hydroxamate uptake protein component A (FhuA) as host for defined Cu(I) NHC or Cu(II) terpyridyl complexes with a maleimide moiety. By covalently bonding these copper complexes to the protein artificial Diels–Alderases based on a membrane protein have been obtained. Results and Discussion Synthesis of the

• contains a cysteine residue at position 545 for conjugation [31], an NHC ligand containing a maleimide function was prepared (Scheme 1). The imidazolium salt 3 was synthesized by nucleophilic substitution of mesityl imidazol 1 with maleimide derivative 2. These salts were used to generate the Cu(I) NHC

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