An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• dihydro-β-carboline derivatives have been synthesized in moderate to good yields using this methodology. Attempts were made towards the conversion of these dihydro-β-carbolines to naturally occurring eudistomin alkaloids. Keywords: Bischler–Napieralski reaction; dihydro-β-carboline derivatives; dihydro

• -eudistomin; eudistomin; keto amide; oxidative amidation; Introduction β-Carboline alkaloids [1] are widespread in plants, animals and some are formed naturally in the biological system. Rinehart et al. [2] reported the isolation of β-carboline alkaloids such as eudistomins [3] and several of its analogues

• from the active Caribbean colonial tunicate Eudistoma olivaceum. β-Carboline alkaloids bearing a substituted phenylacetyl group at C-1 position such as eudistomin T (1) [4], eudistomin R (2a) and eudistomin S (2b) [5] were isolated by Cardellina et al. [6], and these compounds exhibit antimicrobial

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• activities and their applications for pharmaceutical lead discovery. These compounds are the central skeleton of numerous alkaloids [1][2][3][4][5][6][7][8] and have found wide biological applications, e.g., as potent p53–MDM2 inhibitors [9][10][11][12][13][14][15]. Usually, isatin and its derivatives were

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• each other. For compound 30, COMPARE analysis revealed the highest similarities towards tubulin interacting compounds like the vinca alkaloids vinfluine, vincristine, vindesine and the taxoid compound docetaxel. Furthermore, good correlations were detected towards PLK-1 inhibitors. Similar results were

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• Helge Klare Jorg M. Neudorfl Bernd Goldfuss Department of Chemistry, Universität zu Köln, Greinstrasse 4, D-50939 Köln, Germany, Fax: +49(0)221-470-5057 10.3762/bjoc.10.18 Abstract Ten novel hydrogen-bonding catalysts based on open-chain PV-amides of BINOL and chinchona alkaloids as well as three

• in activating a hydrogen-bond-acceptor than commonly employed (thio)ureas. Synthesis of chiral open-chain PV-amides We evaluated both BINOL and chinchona alkaloids as chiral backbones. BINOL is a well-established chiral motif [30], while chinchona alkaloids are sterically very demanding, can be

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• the less hindered α,β-unsaturated ester and subsequent reduction. Alkaloid targets Davies and co-worker [112] were the first to apply the DVCPR to the total synthesis of alkaloids. Anhydroecgonine methyl ester (131, see Scheme 16) is a tropane alkaloid structurally related to cocaine, which can be

• divinylcyclopropane–cycloheptadiene rearrangement has been developed as a versatile method for the construction of seven-membered rings. The utilization in the total synthesis of both sesqui- and diterpenoid natural products as well as in the total synthesis of alkaloids and fatty acid-derived metabolites underlines

• (126) featuring an impressive gold-catalzed cascade reaction and a DVCPR. Davies early example of a formal [4 + 3]-cycloaddition in alkaloids synthesis. Fukuyama’s total synthesis of gelsemine, part 1. Fukuyama’s total synthesis of gelsemine, featuring a divinylcyclopropane rearrangement, part 2

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• ; dasyclamide; gigantamide A; (+)-grandiamide D; natural products; putrescine bisamides; Introduction Putrescine bisamides are one of the important naturally occurring polyamine alkaloids found in open chain and cyclic forms. The genera Aglaia are the richest source of putrescine bisamides. The cyclic 2

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• their inherent rigid chiral structure. The spirooxindolo pyrrolidine and pyrrolizidine frameworks form core units of many naturally occurring molecules possess significant pharmacological activities. Among them are alkaloids such as horsfiline from Horsfieldia superbа [1][2][3], elacomine from Elaeagnus

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• stable [5]. Among them, indole-based propellanes are useful in biology and medicine [6][7][8][9][10][11][12]. In 1963 Djerassi [13][14] isolated fendleridine and 1-acetylaspidoalbidine both of which belong to the aspidoalbine alkaloid family [15][16][17][18][19][20]. Kopsia alkaloids (Figure 2) show a

• . Elution of the column with 5% EtOAc/petroleum ether gave the diketone 4 (27 mg, 76%) as a white solid. The spectral data of this compound is identical with that of compound 4 obtained by the other route. [4.4.2] and [1.1.1]propellanes. Alkaloids containing indole-based propellanes. Retrosynthetic strategy

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• as polyhydroxylated alkaloids or azasugars, are sugar mimics in which a nitrogen atom replaces the ring oxygen of the corresponding monosaccharide (Figure 8) [31][32][33][34][35][36]. Iminosugars can competitively bind to glycosidase enzymes because of their structural resemblance to the terminal

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• ; ring closure; trans-methylation; Introduction Pumiliotoxins (PTXs, 1, Figure 1) such as pumiliotoxin 251D (2) are a subclass of indolizidine alkaloids isolated from the skin secretion of neotropical frogs. A total of 19 members have been isolated and partially characterized [1]. Pumiliotoxins are

• structurally characterized by a (Z)-6-alkylidene-8-hydroxy-8-methylindolizidine ring system, which distinguishes from one to another by the 6-alkylidene side chain [1]. Interestingly, it is known that poison frogs don’t produce the alkaloids themselves, instead, they accumulate alkaloids from dietary alkaloid

• -containing arthropods serving as a chemical defense against predators. It is not surprising that the alkaloids found in poison frogs can also be detected from ants, and most of them show remarkable bioactivities [2][3]. For example, formicine ants have been shown to be an arthropod source of the pumiliotoxin

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• alkaloids; structure–activity relationship; Introduction Hedgehog signaling is involved in embryonic development and plays an important role in the maintenance of stem cells, tissue repair and regeneration in adult organisms [1][2][3][4]. The erroneous activation of hedgehog signaling is tightly associated

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• . Review 1. Pyridines and quinolines The pyridine ring can be considered as one of the simplest yet most important heteroaromatic structures. Naturally occurring in many important compounds such as the vitamins niacin and pyridoxine, the ubiquitous redox system NADP/NADPH and a number of alkaloids

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

• higher hydrolytic and metabolic stability. To the best of our knowledge, there are only a few examples of natural products with a 1,2,4-oxadiazole core or a structure based on it. The 3-substituted indole alkaloids, phidianidines A and B (Figure 1), have been isolated by Carbone et al. from the aeolid

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• purity was observed. Keywords: N-(2,3-dihydroxypropyl)arylamide; nitrogen heterocyclic carbenes (NHC); oxidative esterification of aromatic aldehyde; Introduction Chiral structures with three carbons are an integral part of many biologically active compounds including alkaloids, pharmaceuticals and

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• . This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we

• have limited this review to the most inspiring examples. Within different congeners, we have selected a few members and discussed the synthetic routes in more detail. The putative biosynthetic pathways of the presented isoindole alkaloids are described as well. Keywords: isoindole; isoindoline

• is derived from L-tryptophan (36) [25], indicate a close biosynthetic relationship between these alkaloids. After additional experiments, the authors concluded that lycogalic acid A (38) is the biosynthetic key intermediate for the biogenesis of indolocarbazoles. This hypothesis was verified through

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 1897–1898, doi:10.3762/bjoc.9.223

• , tobacco and cocoa, drugs that all contain alkaloids with stimulating effects. More importantly, starting from their usage in traditional medicine natural products – and today also compounds inspired by natural products – are indispensable in the treatment of various threatening infectious diseases. The

Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

• Lin Yan,
• Zhiqiang Han,
• Bo Zhu,
• Caiyun Yang,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2013, 9, 1853–1857, doi:10.3762/bjoc.9.216

• compounds with chiral quaternary carbon centres containing a fluorine atom. Results and Discussion In the preliminary experiments, we investigated the reaction of α-fluoro-β-ketoester 1a with MBH carbonate 2a as the model substrate, in the presence of several commercially available Cinchona alkaloids as

•  1, entry 2). Next, we screened a series of C2-symmetric bis-Cinchona alkaloids as catalysts under the same conditions (Table 1, entries 3–7). (DHQD)2PHAL showed moderate catalytic activity; 3aa was obtained in 67% yield with 71% ee and 60:40 dr (entry 3). The effects of solvent were then

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• -1 to OC-6). The substituent on the bridgehead nitrogen of cinchona alkaloids has a great impact on the enantioselectivity of the reactions. The catalyst OC-2 with 9-anthracenylmethyl on the bridgehead nitrogen is more efficient than other cinchona alkaloid-derived catalysts for the desymmetrization

• enantioselective desymmetrization of a phospholene meso-epoxide by cinchona alkaloids to P,C-chirogenic 3-hydroxy-2-phospholene derivatives 93 and 94. Among the four main components of cinchona alkaloids, quinidine (OC-57) proved to be the most effective base in the enantioselective rearrangement of epoxide, and

• -aziridines are plentiful and can be found in a diverse set of privileged structures, including cinchona alkaloids-based PTCs, L-proline-derived amino alcohols, chiral phosphorous acids, chiral thioureas, chiral guanidines, and chiral 1,2,3-triazolium chlorides. But for the desymmetrization of meso-epoxides

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• tryptamine derivatives provides access to 3a-(phenylselenyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole derivatives in high yields and with synthetically useful levels of enantioselectivity (up to 89% ee). Keywords: catalysis; chiral phosphoric acid; hexahydropyrrolo[2,3-b]indole; indole alkaloids; natural

• selenoetherification of olefins, whereas the enantioselectivity was not quite synthetically attractive (up to 70% ee) [25]. As chiral 3-substituted hexahydropyrroloindoline is a key structural moiety prevalent in a large number of bioactive indole alkaloids [26][27], direct access to which by selenofunctionalization

Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

• Steven S. Y. Wong,
• Michael G. Brant,
• Christopher Barr,
• Allen G. Oliver and
• Jeremy E. Wulff

Beilstein J. Org. Chem. 2013, 9, 1419–1425, doi:10.3762/bjoc.9.159

• as tetracycle 7) exhibited an unusual fluxional behavior at room temperature, which was ultimately traced to stereochemical inversion at the sp3-hybridized nitrogen. This behavior is consistent with previous examples of fluxional alkaloids, but represents a new structural type that may find

Palladium-catalyzed synthesis of N-arylated carbazoles using anilines and cyclic diaryliodonium salts

• Stefan Riedmüller and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2013, 9, 1202–1209, doi:10.3762/bjoc.9.136

• ., alkaloids) and pharmaceuticals [1]. In addition, the carbazole motif constitutes an immense class of materials in the rapidly growing field of molecular electronics. In particular N-arylcarbazoles have promising electroluminescent properties and have subsequently found diverse applications as hole-transport

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• ; quinazoline alkaloid; Introduction Quinazoline alkaloids are a class of naturally occurring compounds with a range of medicinal properties and have been indicated for use as bronchodilators, vasodilators, anti-inflammatory agents and acetylcholinesterase inhibitors [1][2][3][4][5]. Many of the plants these

• products have been isolated from, such as Adhatoda vasica, Peganum harmala and Evodia rutaecarpa, have been used in folk medicine for centuries [6][7][8][9]. Since the original isolation of vasicine (1, Figure 1) in 1888 [10], the biological properties of this class of alkaloids have been extensively

• studied. A number of synthetic strategies have been employed to gain access to quinazoline alkaloids [5][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Perhaps the most common method involves the condensation of an ortho-aminobenzoic ester with a lactam promoted by phosphoryl chloride

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• expand the scope of the enone aza-[3 + 3] annulation was made in the form of propyleine synthesis as a proof of concept. While synthesis of the enone annulation precursor was successfully accomplished, the annulation proved to be challenging and was only modestly successful. Keywords: alkaloids

• of isomerization and hydrolysis (Figure 1) [34][35][36][37]. The prevalence of six-membered nitrogen heterocyclic motifs in alkaloids renders the development of this aza-[3 + 3] annulation into a powerful strategy a unique opportunity in the field of alkaloid synthesis [1][2][3][4][8][9][10][11][12

• of N-1,4-addition and C-1,2-addition/β-elimination [16][17], effectively leading to a variety of nitrogen heterocyclic motifs, such as 3, which are prevalent among alkaloids (Scheme 1) [16][26][27][28][29][30][31][32]. However, there was a significant deficiency in this annulation: the inability to

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• indole alkaloids comprise a large category of alkaloids with diverse biological activities [1]. Their complex chemical structures and applications in pharmaceuticals have sparked numerous synthetic efforts in the past few decades. Dimeric indole alkaloids such as vinblastine (3) (Scheme 1) still inspire

• leukemia [12][13][14]. Fragmentation of 3 under acidic conditions delivers two structural units, desacetylvindoline and velbanamine (2) [15]. The reassembling of catharanthine (1) and vindoline (5) into the parent alkaloids 3 and 4 by using FeCl3-promoted oxidative coupling supports the biogenesis of

• heterodimeric indole alkaloids [11]. Interestingly, velbanamine (2) was later identified in leaves and twigs of Tabernaemontana eglandulosa in 1984 [16]. Therefore, the syntheses of velbanamine (2) and structurally closely related alkaloids may be important for the syntheses of their dimeric alkaloids. The

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• ; oxindole; oxirane; spiro-epoxyoxindole; spirooxindole; Introduction The spirooxindole unit is a privileged heterocyclic motif that forms the core structure of a large family of natural alkaloids and many pharmacological agents with important bioactivity and interesting structural properties [1][2][3][4][5