Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• hydrolysis transition states as well as having many other interesting properties. They are found in nature as pyrrolidines, piperidines, indolizidines, pyrrolizidines or nortropane alkaloids with a variety of ring substituents, typically hydroxy groups, carboxylic acids and amides [1]. The ability of

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• diverse secondary metabolites with pharmaceutically useful bioactivities. Importantly, members of the genus Streptomyces have been the main source of drug discovery programs due to their high capacity in secondary metabolism including polyketides, peptides, terpenoids, alkaloids, and amino acid

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• for the synthesis of many alkaloids (Figure 1) [16]. To synthesize pyrazinoisoquinoline and its derivatives, various approaches such as the Ugi multicomponent reaction [17] amidoalkylation [18][19], N-acyliminium ion cyclization [20] and a radical cyclization [21] have been reported. To this end

• , recently, we have reported the activation of an imide carbonyl group with TfOH, for the synthesis of tetrahydroisoquinoline (THIQ) and tetrahydro-β-carboline (THBC) skeletons and related alkaloids [22][23][24][25][26]. The present study, describes the synthesis of 4-benzenesulfonylpiperazine-2,6-dione

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• . ComQ lacks homology to cysteine isoprenyltransferases, tryptophan dimethylallyltransferases for cyanobactins [2][37][38] or prenyltransferases for indole alkaloids [39][40][41][42]. However, ComQ shares some homology with farnesyl diphosphate (FPP) synthases and geranylgeranyl diphosphate (GGPP

• ABBA fold and exhibits some similarity to other dimethylallyltransferases for cyanobactins and prenyltransferases for indole alkaloids, but lacks similarity to cysteine isoprenyltransferases and ComQs [2][37][38][39][40][41][42][43][44]. Considering the in vitro prenylation analysis of KgpF together

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• ]. Opatz et al. developed the enantioselective syntheses of various alkaloids using the rhodium catalyst developed by Noyori [88] for the asymmetric transfer hydrogenation of imines. Interestingly, imines are formed from unstable α-aminonitrile intermediates which spontaneously eliminate HCN [89][90][91

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• charge providing ion–dipole interactions with the carbonyl portals of CB[7] as well as its extended π system, that was proposed to cause a higher affinity to the CB[7] due to an increased hydrophobic effect. Moreover, the naphthoquinolizinium ion resembles the quinolizinium-type alkaloids palmatine

• that can thread nicely into the binding site. Notably, the structurally resembling alkaloids berberine (8a) and palmatine (8b), that contain an angularly annelated quinolizinium unit, also bind to CB[7]. But whereas palmatine (8b) has essentially the same binding constant as 2 (Kb = 4.3 × 104 M−1, in

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• modulation, α1a adrenoceptor-selective antagonists, cancer therapy, anti-HIV alkaloids) [12][13][14][15]. The mechanism of the Biginelli cyclocondensation was proposed and investigated by Kappe and is illustrated in Scheme 1a [16]. According to the generally accepted mechanism of the Biginelli reaction

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• [7][8][9][10]. Indole and indazolyl subunits are central to numerous alkaloids and are constituents of many classes of compounds that display a wide range of bioactivities such as antimycobacterial, anti-inflammatory, antihypertensive, anticancer, antidepressant, antidiabetic, antimalarial

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• example MI-63 and MI-219, [15][16][17][18] have demonstrated cellular activity consistent with inhibition of MDM2-p53 binding and have shown in vivo antitumor activity [15][19] (Figure 1). Isoindolinones, belonging to the alkaloids family, are found in many natural products such as vitedoamine A

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• piperidine or a pyrrolidine-based precursor, with few reports of alternative approaches. The approach adopted by our research group to the synthesis of these and related bicyclic alkaloids takes advantage of enaminone chemistry [10][11][12][13][14][15][16][17][18][19]. Our interest in the enaminone manifold

• stems mainly from its ability to display both ambident nucleophilic and electrophilic reactivity, properties that have frequently been exploited in the synthesis of alkaloids and other nitrogen-containing heterocycles [20][21][22][23]. The enaminone and related units that form the basis of our own

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• and TDDFT–ECD calculations. The synthesized flavonoid alkaloids were further characterized by physicochemical and in vitro pharmacological studies. Keywords: absolute configuration; Dracocephalum rupestre; dracocephins A–B; ECD calculation; flavonoid alkaloids; HPLC–ECD; Introduction Flavonoid

• alkaloids are a small subgroup of flavonoids possessing a five- or six-membered nitrogen heterocycle attached to C-6 or C-8 of ring A of the flavonoid moiety. They have been reported to exhibit a wide range of pharmacological activities [1]. Dracocephins A and B were isolated as a mixture of four

• cyclization of the Strecker aldehyde 5 yields the acylaminocarbinol intermediate 6, which readily loses water on protonation, resulting in the N-acyliminium ion 7a/b, a strong electrophilic reagent. Results and Discussion The aim of our work was to synthesize the natural flavonoid alkaloids 2a–d and 3a–d in a

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• materials. The operational simplicity combined with the convenience for introducing substituents to the aromatic rings makes this method useful. Natural indolo[3,2-a]carbazole alkaloids. Retrosynthetic analysis of indolo[3,2-a]carbazoles. Reagents and conditions: (a) H2SO4, MeOH; (b) Ar-NH2, Pd(OAc)2, BINAP

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• ; Introduction The aminal system (N,N-acetal) is the structurally equivalent analogue of the O,O-acetal. In the literature this moiety is found as a core element in various important structures, for example in the naturally occurring alkaloids tetraponerine T1 to T8 from the venom of the New Guinean ant

• with KMnO4 or a mixture of potassium iodide and tert-butyl hydroperoxide (TBHP) give access to quinazolinones and have been reported for the synthesis of the naturally occurring alkaloids deoxyvasicinone, mackinazolinone or rutaecarpine [22][28] (Scheme 2). Besides total oxidation of the aminal core

• , also a partial oxidation towards 3,4-dihydroquinazolines is possible for the case that the oxidation is promoted either by Cu(AcO)2 or by a mixture of elemental iodine and BuLi. These methods allow the synthesis of the partially unsaturated alkaloids vasicine or deoxyvasicine in good yields [22][28

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• compounds having the spiropyrrolidinyloxindole core [14][15][16][17][18]. The 3,3’-spiropyrrolidinyloxindole unit is found in the molecular skeleton of a large family of natural alkaloids with remarkable bioactivity profiles and interesting structural properties [19][20]. Derivatives with the 2,3

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• quaternary and tertiary stereogenic carbon centers on biologically intriguing molecular frameworks with high fidelity. Keywords: ammonium betaine; asymmetric catalysis; Mannich reaction; organocatalysis; oxindole; Introduction Chiral indole alkaloids possessing C-3 quaternary indoline frameworks are an

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• variotii EN-291, an endophytic fungus isolated from the red alga Grateloupia turuturu. The investigation of the chemical constituents of this fungal strain had been performed and as a result, three new oxepine-containing alkaloids with antimicrobial activities [9][10], two new butenolide derivatives with

• DPPH radical scavenging activity [11], and two new prenylated indole alkaloids with cytotoxic activity [12] had been isolated and identified. In an effort to isolate additional analogues that might show similar effects, a larger fermentation was undertaken. This study led to the isolation of two

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• of aroyldiazomethanes 2 and dibenzoyldiazomethane 3c with aminoester 1. Oxidative functionalization of α-СН2-groups in the structure of amines is a rather familiar instrument of organic synthesis, which is widely used for the preparation of amino acids and alkaloids [26][27][28]. Cleavage of σ-С–С

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

• chiral counterions in less polar solvents. Up to 61% ee could be obtained using cinchona alkaloids as catalysts [26]. The subsequent work of Tan and co-workers with guanidine catalyst 8 achieved enantioselectivities as high as 99% ee [19]. In recent years functionalized chiral amines have been

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• [4]. Oxygen heterocycles are mainly found in carbohydrates, polyketides, peptides and terpenoids. Nitrogen heterocycles are part of peptides and alkaloids. Both can of course also occur in the respective hybrid natural products. Sulphur-containing heterocycles are present in few polyketides and more

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• recently gained immense importance. 2-Oxindoles having all carbon quaternary centres at the pseudobenzylic position are common structural scaffolds in many naturally occurring alkaloids of biological relevance [22][23][24][25]. These heterocyclic motifs especially exist in indole alkaloids with a wide

• focussed our attention to prenylated, reverse-prenylated, and geranylated hexahydropyrrolo[2,3-b]indole alkaloids showing broad biological activities [55][56][57][58][59][60][61]. For the synthesis of these compounds, we thought of utilizing the Pd-catalyzed decarboxylative strategy to install the prenyl

• the results are summarized in Figure 5. Interestingly, under this conditions, we can synthesize a variety of 2-oxindoles 8 in moderate to good yields. There are a large number of indole alkaloids bearing a 3-arylated-2-oxindole moiety that are known for their various biological activities [65][66][67

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• alkaloids of marine origin. Additional features of this route include the stereoselective generation of the central amine core with an appending quaternary center by an asymmetric addition of a Grignard reagent to a chiral tert-butanesulfinyl ketimine following an optimized Ellman protocol and a cross

• bromopyrrole alkaloids has attracted great interest from synthetic chemists and a variety of elegant total syntheses has been reported [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Inspired by an innovative concept for heterocycles synthesis recently developed in our group [26][27][28][29

• the chiral amine core of these alkaloids. For the synthesis of the nitrogen appending the quaternary center we tested a method developed by the Ellman group [46][47], which relies on an asymmetric addition of organometallic reagents to enantiopure tert-butanesulfinyl ketimines of type 29 and 30

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• murine leukemia cells (IC50 0.28 μg/mL) [1]. It is a member of the manzamine alkaloids and has an exquisite molecular structure comprising a 6,6,6,11,13 pentacycle possessing 4 stereogenic centres including one quaternary centre (Figure 1). In 1992, two years before its isolation, Baldwin and Whitehead

• , in their landmark paper entitled ‘On the Biosynthesis of Manzamines’ postulated that keramaphidin B was a common intermediate in the biosynthesis of the manzamine alkaloids [2]. Several years later, Baldwin and co-workers synthesised keramaphidin B following a biomimetic pathway via an intramolecular

• manzamine alkaloids with a particular emphasis on the development of novel catalytic methods for simplifying their syntheses [5][6][7][8][9][10]. Owing to keramaphidin B’s attractive structure combined with its interesting biological profile and the lack of an efficient method for its synthesis, we selected

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

• catalysts Cinchona alkaloids and their derivatives have been widely used as chiral catalysts in many reactions [44] and also show synthetic utilities in the synthesis of enantiomerically pure 3-substituted 3-hydroxyoxindoles. In 2013, Wu and co-workers reported the cinchona alkaloid (cat. 14)-catalyzed

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• acceptors in reactions promoted by bifunctional Brønsted bases. 1.2.1 Nitroalkenes as acceptors. Investigation of the base-catalyzed Michael addition reaction of 2-thio-1H-imidazol-4(5H)-ones 4 to nitroalkenes 5 [55] revealed that cinchona alkaloids such as quinine, (DHQ)2Pyr or even thiourea tertiary amine

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• sciences. Besides, the annelated cyclic indenes containing N or O heteroatoms are the main structural frameworks of several natural alkaloids [1], while indenopyran derivatives were found to be valuable substrates for the synthesis of various compounds with biological activity [2][3]. Some indeno[1,2-c