Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• , such as lukianol A (1) and lukianol B (2) (Figure 1) [8][9][10]. Lukianol B (2) was found to be the most potent human aldose reductase (h-ALR2) inhibitor in thousands of marine natural products screened [11]. The ningalin B alkaloid 3, having an isomeric pyrrolo-oxazinone skeleton, possesses antitumor

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• . Tashiromine is a natural indolizidine alkaloid isolated from Maackia tashiroi (1990). Strategies for the synthesis of indolizidine derivatives have received considerable interest from synthetic and medicinal chemists (Figure 2). A number of synthetic approaches have been described earlier for construction of

• concentrated under reduced pressure. The crude oil was purified by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH 90:8:2 or CH2Cl2/MeOH/NH4OH 90:5:5) to give the alkaloid. Ethyl (1R*,2S*)-2-(benzyloxycarbonylamino)cyclooct-5-enecarboxylate ((±)-3) A colourless oil (Rf 0.6, n-hexane/EtOAc 4:1); yield

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• , Trost and Genêt used a careful O-acetylation of an amino alcohol alkaloid intermediate with acetic anhydride in CH2Cl2 acidified with HClO4 as part of a total synthesis (Scheme 15) [88]. In the footsteps of Bretschneider, chemoselective O-acetylation of natural product amino alcohols also inspired

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• tools in organic synthesis. Among numerous applications they are applied as chiral ligands [1], as catalysts for various asymmetric transformations [2], and as building blocks for alkaloid and pharmaceutical drug synthesis [3][4]. The increasing number of applications leads to a growing interest in the

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• specific delivery of drugs to the desired place of action lowers the adverse effects associated with conventional chemotherapy tremendously [3]. Therefore, much effort is continuously being made to develop novel drug-carrier systems. (S)-Camptothecin (CPT) is a natural cytotoxic quinoline alkaloid with a

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• afforded the carbonyl compound and the 5,6 and 6,6-ring systems of the target compounds. Toyooka and co-workers have designed a route to both enantiomers of the quinolizidine poison frog alkaloid 195C. Key to the success of their synthetic endeavour was the preparation via direct anodic oxidation of

• glycine cation equivalents. Steckhan and co-workers have previously demonstrated the power of electrosynthetic chiral glycine equivalents [99][100]. Combination of technology and natural product analogue synthesis Lastly, Ley and co-workers have recently reported the expedient synthesis of indole alkaloid

• oxidation used in the preparation of the poison frog alkaloid 195C [80]. Preparation of iminosugars using an electrochemical approach [81]. The electrosynthetic preparation of α-L-fucosidase inhibitors [84][85]. Enantioselective synthesis of the anaesthetic ropivacaine 85 [71]. The preparation of

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• potential carcinogenic and mutagenic properties of some derivatives (EB and analogues), which had negative influence on biomedically-oriented studies of the complete phenanthridine class till the end of the 20th century. However, discovery of phenanthridine alkaloid analogues and in parallel new studies of

• bioactivity-guided fractionation, the bioactive compound chelerythrine (21, a quaternary benzo[c]phenanthridine alkaloid) was isolated from Chelidonium majus L. [103]. In addition to strong antihelmintic activity (against D. intermedius), chelerythrine also showed antimicrobial, antifungal and anti

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• synthetic approaches have been reported [61][62]. One popular target in this family is aspidospermine (36, Scheme 8). Although its medicinal potency is inferior to other members of the class, this alkaloid has served as a proving ground for many synthetic chemists. In 1989, Meyers reported an

• enantioselective synthesis of the (4aS,8aR,8S)-hydrolilolidone core 37 [63][64] present in aspidospermine (36), and thus a formal total synthesis of the alkaloid itself, intercepting Stork’s classic route [61]. One precursor described in the core synthesis is enone 38, which bears the quaternary stereocenter of

• [71]. It features a tetracyclic scaffold with a nine-membered ring and an all-carbon quaternary stereocenter. This alkaloid is a microtubule-disrupting agent that displays similar cellular effects to paclitaxel [72][73]. Because of its biological activities and potential pharmaceutical use, many

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• , Kwon and Andrews completed the first enantioselective total synthesis of the indole alkaloid (+)-ibophyllidine in 15 steps and 13% overall yield from N-Boc-indole-3-aldehyde (Scheme 32) [66]. This approach was the first non-formal total synthesis of a complex natural product employing phosphine

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• Catharanthus roseus [40] has been cloned and heterologously expressed in baculovirus-infected insect cells [41]. This cytochrome P450 monooxygenase belonging to the CYP76B family has been demonstrated to be involved into the biosynthesis of the alkaloid secologanin, and produced 8-hydroxynerol. It should be

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• used to carry out an asymmetric alkylation reaction (Scheme 4). The monoalkylation of phosphine–borane complex 15 was performed in the presence of the Cinchona alkaloid ammonium salt 16 [50]. However, the enantioselectivity of the reaction was low. Imamoto et al. prepared a new tetraphosphine ligand 19

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• 86% yield and 88% ee (Table 5, entry 9). A recently reported similar reaction catalyzed by Cinchona alkaloid-based primary amine catalyst requires high catalyst loading and is only suitable for N-unprotected isatylidenemalononitrile derivatives [5]. In contrast, our methodology is suitable for both N

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• -a]isoquinolinone which has been isolated from Berberis darwinii [1][2][3]. Cryptolepine is an indolo[3,2-b]quinolone alkaloid found in west African shrub Cryptolepis sanguinolenta, a plant used in traditional medicine for the treatment of malaria [3]. This alkaloid has shown potent antiplasmodial [4

• ] and anticancer [5] activities. The bioactive β-carboline alkaloids canthinone [6] and vinpocitine [7] also bear these substructures. Vinpocetine is a dehydrated derivative of the natural alkaloid of vincamine [8]. It is reported to have cerebral blood-flow enhancing [7] and neuroprotective effects [9

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

• activity. Xestomanzamine A (3) [5] is a β-carboline alkaloid with an 1-methyl-1H-imidazole-5-acyl group at the C-1 position and was isolated from the Okinawan marine sponge Xestopongia sp. The other β-carboline alkaloids reported in the literature are fascaplysin (4) [7], eudistomin A (5a) [3], harmine (5b

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

• involving 1-aza-4-borono-1,3-dienes 28 as key starting materials for the preparation of α-hydroxyalkylpiperidines. These scaffolds are present in several natural products, particularly in the alkaloid family of palustrine. The tandem process started with the hetero-[4 + 2]-cycloaddition of an hydrazonodiene

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

• and reductive amination after Boc-deprotection to yield the desired natural product 131 in only five steps. Perhaps one of the most prominent alkaloid syntheses using a DVCPR was carried out by Fukuyama and coworker [118][119][120] and targeted gelsemine (146, see Scheme 17 and Scheme 18), an alkaloid

• . Removal of the MOM-protecting group followed by reduction of the amide concluded Fukuyama’s total synthesis of gelsemine (146). An approach similar to Davies formal [4 + 3]-cycloaddition [81] was used by the group of Kende [130] to access the alkaloid isostemofoline (158, see Scheme 19) [131]. Rhodium

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

• vincristine-resistant KB cancer cells [23][24]. Minfiensine alkaloid [25][26][27][28][29][30][31] containing a novel 1,2,3,4-tetrahydrocarbazole ring skeleton shows anticancer activity [32]. König and co-workers identified some propellane derivatives as cannabinoid CB1 receptor antagonists [33], which are

• potential drugs for the treatment of schizophrenia and alcohol addiction [34]. However, the synthesis of indole alkaloid derivatives containing a propellane ring system is a challenging task due to the presence of quaternary centers involved with these systems [35]. We envisioned a new synthetic route to

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

• derivatives bearing a pendant nitrogen nucleophile, and the source of chirality was a substoichiometric quantity of the cinchona alkaloid derivative (DHQ)2PHAL (70). This method was shown to work very well with several different pendant nucleophiles, but the N-acetamido nucleophile was found to be optimal

• , giving the corresponding product 71 in an impressive 92% ee. Elucidating the mechanism of chiral induction in this type of process is not straightforward, but preliminary experiments showed that associative complexation between the substrate 69 and the alkaloid catalyst 70 may account for the observed

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

• 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

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

• uptake inhibitor originally developed over 20 years ago by Novo Nordisk and Abbott and is currently used as anticonvulsant in the treatment of epilepsy. For a long time it has been recognised that the simple core alkaloid structures as found in nipecotic acid (2.37), guvacine (2.38), β-homoproline (2.39

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• sometimes offer competitive solutions regarding the synthesis of challenging chiral amine structures [9][22]. Furthermore, it is common that alkaloid or amine containing pharmaceutical drug syntheses proceed through imine intermediates that lead to diastereomeric amine products [36][37][38][39][40]. With

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

• have a huge potential for the development of new chemistry. Review Indolocarbazoles. Staurosporine (26) was the first member of the indolocarbazole alkaloid family to be discovered by Ōmura from Streptomyces staurosporeus at the Kitasato Institute in 1977 [16]. Over the past 35 years, more than 60

• subclasses. The first comprises two linkages, exemplified by (+)-staurosporine (26) and (+)-K252a (27), whereas the second class contains only one glycosidic bond as found in rebeccamycin (28) and holyrine A (29). Selected members of the indolocarbazole alkaloid family are depicted in Figure 2. The strong

• , Vedejs), the convergent approach reported by Myers allows a modular entry to diverse members of the cytochalasin alkaloid family [68]. As proof of concept, the macrolactone cytochalasin B (52) and the carbocyclic cytochalasin L-696,474 (78), a potent HIV-1 protease inhibitor [69][70][71][72], were

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• alkaloid; total synthesis; Findings (−)-Epimyrtine, isolated from Vaccinium myrtillus (Ericaceae) [1][2], is a quinolizidine alkaloid. This alkaloid family exhibits potential pharmacological properties such as anticancer, antibacterial, antiviral and anti-inflammation activities [3][4][5]. This alkaloid

• has been a target of interest for synthetic chemists because of its structural simplicity among the family of quinolizidine structures. Since it has been isolated, numerous total syntheses of this alkaloid in racemic form have been reported in the literature. However, only a few asymmetric syntheses

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

• and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, Singapore 637371 10.3762/bjoc.9.216 Abstract In the presence of a commercially available Cinchona alkaloid as catalyst, the asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates, with α-fluoro-β-keto esters as

• with hetereoaromatic groups, such as thiophene and furan (Table 2, 2n–o). Conclusion We have developed an asymmetric allylic alkylation of MBH carbonates with α-fluoro-β-ketoesters, catalyzed by a commercially available Cinchona alkaloid. Several fluorinated adducts, with chiral quaternary carbon