Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• Hapalindole/ambiguine alkaloids, isolated from cyanobacteria, are composed of the total C15 prenyl moieties derived from dimethylallyl diphosphate (DMAPP) and geranyl diphosphate (GPP), and cis-indolylvinyl isonitrile 1 (Figure 2A) [15]. This natural product family includes structurally diverse compounds with

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• for such rigid systems are macrocycles which stem from Lissoclinum cyclopeptide alkaloids (Figure 1) [2][3]. Here, the required recognition units can be introduced via the amino acid side chains or via the side chains of the azole rings. The orientation and the distance between the recognition units

• -D3 [56][57] as well as the def2-TZVP [60][61] basis set. Some examples for artificial C2- and C3-symmetric platforms based on Lissoclinum cyclopeptide alkaloids. a) Principle of a chiral foldable platform and container based on Lissoclinum cyclopeptide alkaloids. b) Switchable molecular platform 4

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• applied in squalestatin syntheses as highlighted above, the monoalkylated tartaric acid motif is also directly present in several natural products, such as hydroxybenzyl-substituted piscidic acid (42) and congeners (fukiic and cimicifugic acids) [50], and the Cephalotaxus alkaloids isoharringtonine (43

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

• ] and zinnimidine [4] (Figure 2) are simple isoindolinone alkaloids, for which total syntheses have been reported [5], and nuevamine (Figure 2) is an isoindoloisoquinoline alkaloid [6][7]. Moreover, in this last decade, new compounds such as impatien A [8] (Figure 2) or daldinans B and C [9] have been

• discovered. Similarly, the 2-oxindole framework is prevalent in a wide range of natural products [10]. For example, convolutamydines [11] are alkaloids containing a dibromohydroxyoxindole moiety, isolated from the Floridian bryozoan Amathia convulata, while coerulescine [12] is an oxindole alkaloid isolated

• using simple substrates and reagents. γ-Lactam-derived structures considered in this review. Alkaloids containing an isoindolinone moiety. Alkaloids containing the 2-oxindole ring system. Drugs and biological active compounds containing an isoindolinone moiety. Drugs and biologically active compounds

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• considered as the analogues of both 3,3’-spirooxindole and 2-aminoimidazole marine sponge alkaloids. Keywords: 2-amino-4-arylimidazole; (2-amino-4-arylimidazolyl)propanoic acid; isatin; Meldrum’s acid; multicomponent reactions; pyrrolo[1,2-c]imidazole; 3,3’-spirooxindoles; Introduction Heterocyclic

• of Leucetta Sp. and Clathrina Sp. are presented by achiral imidazole alkaloids from the group of benzyl substituted 2-aminoimidazole (dorimidazole A (I), naamine A (II)), fused cyclic systems (2-amino-2-deoxykealiiquinone (III)) and spiro-linked compounds ((−)-spirocalcaridine B (IV)) [2]. Agelas Sp

• . are a source of alkaloids with core structures containing simultaneously pyrrole carboxamide and 2-aminoimidazole moieties such as the simple achiral compound oroidine (V) and spatially organized molecules in a complex manner with a large number of chiral centres like (−)-palau’amine (VI) [3

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• recycle catalysts. However, only a limited number of organocatalytic moieties and functional groups have been attached to CD scaffolds so far. Cinchona alkaloids are commonly used to catalyze a wide range of enantioselective reactions. Thus, in this study, we report the preparation of new α- and β-CD

• derivatives monosubstituted with cinchona alkaloids (cinchonine, cinchonidine, quinine and quinidine) on the primary rim through a CuAAC click reaction. Subsequently, permethylated analogs of these cinchona alkaloid–CD derivatives also were synthesized and the catalytic activity of all derivatives was

• disubstituted CD derivatives performed similarly to monosubstituted CDs. Therefore, these new CD derivatives with cinchona alkaloids effectively catalyze asymmetric allylic aminations and have the potential to be successfully applied in other enantioselective reactions. Keywords: asymmetric allylic amination

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• alkaloids, which found wide application in some regions as food-stuff and medical supply [33]. The method described in the present study opens a straightforward access to their benzyloxy analogues, potentially bioactive compounds, which have not been known yet. Experimental General information: Solvents and

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• Group, Departments of Chemistry and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel, Belgium 10.3762/bjoc.15.18 Abstract Selectively methylated analogues of naturally occurring 2-heptyl-4(1H)-quinolones, which are alkaloids common within the Rutaceae family and moreover

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

• application as advanced intermediates in the total synthesis of Lycopodium alkaloids [3][4][5][6], 3a-substituted 2,4-dicarbonyl compounds being particularly useful in this field. The synthetic approaches toward these versatile building blocks (i.e., compounds with the functionalization pattern A) are

• (generated by Me3SiSnBu3 and CsF). As a continuation of our work on the synthesis of Lycopodium alkaloids [23][24][25][26], we hypothesized that decahydroquinoline 1, a versatile building block for the synthesis of phlegmarine-type alkaloids, available in both enantiomeric forms, could also serve as an

• intermediate toward other Lycopodium alkaloids (e.g., fawcettimine). Thus, we surmised that building block 1 could be a new precursor of 3a-substituted hydrindan-2,4-diones (Scheme 1). This type of compounds, when adequately functionalized, has been used as advanced intermediates for the synthesis of the

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• units in bioactive natural products and pharmaceuticals. Some of these propellanes exhibit intresting properties like antibiotic, antifungal, anticancer, platelet-activating factor antagonistic and antibacterial activities. The propellane skeleton is present in many alkaloids such as aknadinine (1

• , 141.4, 140.4, 140.2, 131.2, 128.0, 127.9, 127.2, 127.1, 127.0, 126.5, 125.6, 125.2, 57.4, 51.5, 30.2 ppm; HRMS (ESI, Q-ToF) m/z: [M + K]+ calcd for C90H63N3O6·K, 1320.4348; found, 1320.4344; IR (neat) max: 2328, 1708, 1383, 837, 690 cm−1. Various alkaloids containing propellane frame work. Selected list

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• , Shanghai 200444, P. R. China 10.3762/bjoc.14.198 Abstract A water-soluble 2,2′-biphen[4]arene (2,2’-CBP4) containing eight carboxylato moieties was synthesized and characterized. Its complexation behavior towards two alkaloids, palmatine (P) and berberine (B), was investigated by means of fluorescence and

• of isoquinoline alkaloids‘ family, P and B can produce singlet oxygen (1O2) and oxide biological substrates under light, and thereby have applications in photodynamic therapy (PDT) [48][49][50]. However, their low quantum yields limit such applications, which could be potentially improved or restored

• ). To examine the fluorecence behavior and to quantitatively assess the complexation of the two alkaloids and 2,2’-CBP4, spectral titrations of P/B and 2,2’-CBP4 were performed in the phosphate buffer solution of pH 7.4 at 298 K. As can be seen from Figure 2 and Supporting Information File 1, Figure S10

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

• compounds have been employed as important synthetic intermediates for the construction of biologically active molecules such as histrionicotoxins and the cytotoxic marine alkaloid fasicularin [84]. In 2010, Honda [85] reported the synthesis of isoquinoline alkaloids possessing spirocyclic framework using

• PIDA (15) as an electrophile in hexafluroisopropanol solvent. The p-substituted phenolic compound 48 was used as starting material for the construction of spirolactam 49 in 69% yield (Scheme 15). This is an important intermediate in the synthesis of various naturally occurring alkaloids such as

• an electrophile and trifluoroethanol (TFE) as the solvent at room temperature (Scheme 35). Compound 97 was further used as substrate for the synthesis of discorhabdin alkaloids [106][107]. In 1996, Kita and co-workers [108] developed an intramolecular cyclization of ortho-substituted phenols 98 to

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• architectural extreme are: the ecteinascidins, antitumor tetrahydroisoquinoline alkaloids from the colonial Ascidian Ecteinascidia turbinata as exemplified by ecteinascidin 729 (4) [6]; ulbactins F (5a) and G (5b), two polycyclic thiazoline congeners isolated from a culture extract of a sponge derived

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• enantiomeric ratio of 79:21. This method can be easily performed in large scale. In addition, the structure–activity relationships for the cinchona alkaloids catalysts were elucidated. Experimental All solvents and reagents were of commercial sources and used without further purification. Melting points were

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

• catalytic amounts of chiral phase-transfer agents [32][33][34]. Although the literature contains examples of calixarene derivatives used as phase-transfer catalysts (PTCs) [35], the first asymmetric quaternary ammonium salts derived from cinchona alkaloids based on the calixarene skeleton were prepared by

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

• products were converted into useful intermediates for the synthesis of pyrroloindoline alkaloids and related drugs, such as psychotrimine and (+)-folicanthine. Later in 2016, Trivedi et al. reported the synthesis of chiral 3-amino-2-oxindoles through the Mannich reaction of N-Boc-isatin imines 3 with 1,3

• ligands and organocatalysts. For example, remarkable enantioselectivities of up to 94 to >99% ee have been reported in recent examples of Mannich reactions promoted by organocatalysts, as varied as cinchona-alkaloids, squaramides, phosphoric acids, simple primary amines and L-diphenylprolinol

• organocatalyzed by cinchona-alkaloids, and unprecedented Friedel–Crafts reactions of isatin imines with naphthols and hydroxyquinolines promoted by cinchona-alkaloid-derived thioureas and cinchona-alkaloid-derived squaramides. Slightly lower enantioselectivity levels of up to 94% ee were described in aza-Henry

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• -piperidines are attractive intermediates because they easily can be transformed to a variety of alkaloids having a piperidine skeleton. In our preliminary study, we found the indirect cation pool method suitable for the generation and accumulation of N-acyliminium ions. Therefore, the reaction of N-Boc-4

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• , promoting mitotic halt and consequently cell death [93]. The difference with other known drugs that act on microtubules (vinca alkaloids) is that paclitaxel does not induce the disassembly of microtubules but boosts the polymerization of tubulin [94]. Sites available in PTX for the formation of PDCs are

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

• -transfer catalyst; 3-substituted isoindolinones; Introduction Isoindolinones I (Figure 1), e.g., 2,3-dihydro-1H-isoindol-1-ones, also called phthalimidines are bicyclic lactams whose molecular structure is the basis of a wide range of alkaloids and biologically active compounds [1][2][3][4][5][6][7][8][9

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• compounds. Wilson et al. successfully achieved the total synthesis of xyloketals 17 and 18, including cycloaddition of substituted dihydrofurans and 1-(2,4-dihydroxy-3-(morpholinomethyl)phenyl)ethanone via o-QM intermediates [69]. Osyanin et al. reported the synthesis of Uvaria scheffleri alkaloids

• of Evodia rutaecarpa alkaloids, starting from 6-methoxy-4,9-dihydro-β-carboline and various substituted 1-aminoalkyl-2-naphthols [84] (Scheme 5). Reactions with electron rich aromatic compounds The formation of aza-o-QMs is also possible, if the initial phenolic Mannich base bears an aromatic moiety

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• stereocontrol in alcoholytic catalytic asymmetric desymmetrizations of meso-cyclic anhydrides is of special interest [1][2][3][4][5][6][7]. Major families originating from natural products include cinchona alkaloids [8][9][10][11][12][13][14][15][16][17] and proteinogenic α-amino acids such as proline [18][19

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• (quindoline) system is present in numerous alkaloids of plant origin representing several biological activities and used in traditional tropical medicine for the treatment of various diseases, particularly malaria [1][2][3][4][5]. Further development revealed the potential of synthetic quindoline derivatives

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• ). Previously, Shibata et al. reported a cinchona alkaloid/Me4NF-catalyzed nucleophilic enantioselective trifluoromethylation of carbonyl compounds [33][34][35]. Initially, we tried to conduct the reaction of 2-cyanobenzaldehyde (2) with CF3–SiMe3 in the presence of cinchona alkaloids 9/TMAF combination (Table

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• considerable relevance in drug development, since it is found in both complex [1] and “simple” alkaloids (variously substituted derivatives of the native isoquinoline) isolated from different plants [2], and antiviral and antimicrobial activities have been found for numerous isoquinoline alkaloids [3]. Further

• of the direct methylation of electron-deficient N-heterocycles have been reviewed [9]. In a project aimed at the synthesis of tri- and tetracylic alkaloids containing the isoquinoline scaffold, we were interested in isoquinoline building blocks which bear a methyl group at C1, since this group should

• , due to its intrinsic C–H acidity, open opportunities for further functionalization. Since most isoquinoline alkaloids bear hydroxy and/or methoxy substituents at the positions 6 and 7, we regarded 7-hydroxy-6-methoxy-1-methylisoquinoline (1) as well as analogues containing a protected 7-hydroxy group