A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• four diastereomers can help to assign their relative configurations. This method was exercised on a set of diastereomeric Cinchona alkaloid derivatives, where 13C NMR data always identified the proper configuration. The presented approach is also an attempt to quantify the assignment by exclusion

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• Ottenheijm in the total synthesis of an analogue of the tryptophan-containing natural alkaloid neoechinulin B (indole 77) [67][68] (Scheme 28). At the initial stage, N-methylindole was alkylated with ethyl bromopyruvate oxime and sodium carbonate to give adduct 78, which was then transformed into N

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• ][16][17][18][19][20]. Following the pioneering reports of Wynberg et al. [25] and Merck scientists [26] who employed cinchona alkaloid-derived quaternary ammonium salts for asymmetric epoxidations [25] and the α-methylation of a phenylindanone derivative [26] in the late 1970s, early 1980s already

• nucleophiles dates back to 2002, when Kim and Park described the first use of cinchona alkaloid-based quaternary ammonium salts A (i.e., derivative A1) for the enantioselective α-fluorination of β-ketoesters 1 by using N-fluorobenzenesulfonimide (NFSI, 2) as the fluoride-transfer reagent [73] (Scheme 2). By

• fluorination reaction [78]. The groups of Duan and Lin have also very heavily been engaged in the systematic design of highly active bifunctional cinchona alkaloid-based ammonium salt catalysts that contain an additional H-bonding donor [43][44]. Very impressively, they succeeded in synthesizing and testing

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• conditions were not well tolerated by few sensitive groups, most of the β-carbolines were successfully prepared utilizing this procedure, including the alkaloid harmine with 99% yield. The final product precipitates at the end of the reaction and hence required minimum purification. Organocatalytic aerobic

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• the synthesis of the alkaloid bianfugecine (6, Scheme 4), which contains only one methoxy group at ring B. Until now, only one partial synthesis of this alkaloid is described in the literature. Kunitomo et al. [30] obtained alkaloid 6 by hydrogenolytic demethoxylation of alkaloid menisporphine (2

• ) with H2/PtO2 in acetic acid. Unfortunately, upon cyclization of the carboxylic acid 11c, obtained by acidic hydrolysis of ester 10c, with Eaton’s reagent alkaloid 6 could be isolated in only very poor yield (7%). Other established cyclization methods starting from methyl ester 10c were tested in order

• and N-2 of the isoquinoline moiety, thus is kept away from C-8’. In contrast, we found in previous investigations on the synthesis of the pyridoacridone alkaloid demethyldeoxyamphimendine [21], that an ester group located at a comparable position (suitable for forming a chelate in cooperation with a

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• reported by Pelletier and Caventou, the founding fathers of alkaloid chemistry, in 1818 [4], but the nature of its irritant principles remained obscure and controversial until 1930, when Flaschenträger unambiguously characterized the inflammatory fraction of the oil as a mixture of esters of a crystalline

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• strategies with chiral transition metals [27][28][29][30][31][32][33], organocatalysts such as secondary amines [34][35][36], nucleophilic phosphines [26][37][38][39][40][41][42][43][44], tertiary amines [45], N-heterocyclic carbenes (NHCs) [46][47][48], and cinchona alkaloid derivatives [25][28][49][50

• variety of organocatalysts (a–f) were investigated in CH2Cl2 at −20 °C for 12 h to evaluate their ability to promote the transformation (Table 1, entries 1–6). When cinchona alkaloid-derived catalyst a and quinine-derived amine catalyst b were tested, however, poor yields or ee values were obtained

Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

• Qin Zhu and
• Xinyu Liu

Beilstein J. Org. Chem. 2017, 13, 1168–1173, doi:10.3762/bjoc.13.115

• -52-3 has an enhanced substrate specificity towards 12-epi-hapalindole C (1) in comparison to WelO5 in H. welwitschii UTEX B1830. This allowed us to define the origin of the varied chlorinated versus dechlorinated alkaloid structural diversity between the two welwitindolinone producers. Furthermore

• engineering and evolution of these proteins for biocatalyst application. Keywords: alkaloid biogenesis; biosynthetic divergency; C–H activation; halogenase; non-heme iron enzyme; Introduction Carbon–halogen (C–X) bonds are prevalent structural motifs in modern agrochemicals, pharmaceuticals and bioactive

• ], analogous oxidative functionalizations with halogens via C–H activations remain challenging that need to be addressed [9][10][11]. Recently, during the systematic investigation of hapalindole-type alkaloid biogenesis [12][13][14][15][16][17][18][19], we discovered a family of Fe/2OG-dependent halogenases

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• effective synthetic protocol to access [6,6]-bicyclic lactone moieties through a regio- and stereoselective intramolecular Mizoroki–Heck cross-coupling reaction followed by a 6π-electrocyclization. This method enabled the first synthesis of the elusive CD fragment of the Erythrina alkaloid DHβE. Preliminary

• challenging [6,6]-bicyclic lactone fragment in general through an expedient regio- and stereoselective Mizoroki–Heck cyclization approach. This method enabled the synthesis of the elusive and volatile CD fragments ([6,6]-bicyclic lactones 9 and 26) of the Erythrina alkaloid DHβE. This allowed the

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• (±)-oxomaritidine (gas–liquid–solid reaction) Baxendale et al. have developed a multistep synthesis for (±)-oxomaritidine, a cytotoxic alkaloid of the amaryllidaceae family of natural products [9] (Scheme 4). The process involved seven reaction steps out of which the first two reactions were carried out in parallel

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• , nannozinone B (5, Figure 2), containing a pyrrolopyrazinone moiety was isolated from a myxobacterium, Nannocystis pusilla [11]. The alkaloid peramine (6, Figure 2), isolated from endophyte-infected perennial ryegrass, has feeding deterrent activity against insects [12][13]. An efficient and straightforward

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• ] nucleophiles using bifunctional cinchona alkaloid catalysts. The Sasai and Enders groups used a phosphinothiourea to enable a Rauhut–Currier reaction to form bicyclic enones [16]. The Tian and Lin group used alkyne-tethered cyclohexadienones in an arylrhodation/conjugate addition sequence that

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• number of cinchona alkaloid-derived ligands which allow the dihydroxylation of alkenes of almost all substitution patterns with high enantioselectivity. Noteworthy is that the SAD is not limited to only E-allylic alcohols in its choice of substrates as is the SAE process. Moreover, the SAD is much more

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

• (15i–k). A series of aliphatic α-iminonitriles also gave good results (15n,o). Notably the labile dimethylacetal group tolerates this two-step transformation (15m). Using this protocol, the authors described a total synthesis of (±)-isoretronecanol (19), a pyrrolizidine alkaloid (Scheme 9). In this

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

• of the naturally occurring indolizidine alkaloid (±)-tashiromine and its unnatural epimer (±)-epitashiromine are demonstrated through the use of enaminone chemistry. The impact of various electron-withdrawing substituents at the C-8 position of the indolizidine core on the preparation of the bicyclic

• system is described. Keywords: alkaloid; enaminone; epitashiromine; indolizidine; tashiromine; Introduction Tashiromine (1) is a monosubstituted indolizidine alkaloid originally isolated from the Asian deciduous shrub Maackia tashiroi [1] and subsequently from the genera Poecilanthe [2] and Crotalaria

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

• chemistry, DNA intercalation, etc.) or in synthetic tetrahydroquinazolines as cholinesterase (ChE) inhibitors [15][16][17] as well as ChE inhibitors based on the scaffold of the naturally occurring alkaloid physostigmine from the calabar bean physostigma venenosum [18][19] (Figure 1). This is just a small

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

• natural products, have been used as chiral phase-transfer catalysts [12][13]. Bicyclic guanidines with five-membered rings are also known from the alkaloid isoalchornein [14][15]. In subsequent years, synthetic compounds (6–9) of this structural type have been developed as chiral Brønsted bases [16][17

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• attention, and numerous catalytic enantioselective methods using chiral catalysts have been reported [9][10][11][12][13]. Oxindole and its derivatives can be exploited as important synthons to synthesize various alkaloid natural products and biologically active compounds [14][15][16]. In particular, 3,3

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

• mechanism is reminiscent of the formation of a tetrahydropyridine ring by the berberine bridge enzyme in plant alkaloid biosynthesis. It starts with S-adenosyl-L-methionine (SAM)-dependent methylation of the secondary hydroxy group in 81 by the O-methyltransferase Leu14 (Scheme 14a) [71][72][73][74

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

• addition; keramaphidin B; nitro-Mannich lactamisation cascade; Introduction Keramaphidin B (1) is a marine alkaloid first isolated by Kobayashi in 1994 from the Okinawan marine sponge Amphimedon sp and has been shown to be cytotoxic against KB human epidermoid carcinoma cells (IC50 0.28 μg/mL) and P388

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

• , unprotected isatins failed to gave the desired products under the same conditions. As shown in the binding model, the catalyst activated the carbonyl groups through hydrogen bonds, while the allyltributyltin reagent attacked the 3-carbonyl group from the Si face, forming (R)-isomers. Cinchona alkaloid

• 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

• same group reported the organocatalytic asymmetric addition reactions of isatins with electron-rich aromatics sesamols using the cinchona alkaloid-derived thiourea catalyst (cat. 17) under mild conditions. In the presence of 10% catalyst, sesamols reacted with isatins smoothly in tert-butyl ether at

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• organocatalysis and metal catalysis for the construction of this type of structures. For example, Chen et al. reported the first organocatalytic enantioselective amination reaction of 2-oxindoles catalyzed by biscinchona alkaloid catalysts [8]. Zhou [9][10] and Barbas [11][12], have independently reported similar

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• in the chiral induction of the process. The authors proposed the transition state TS14, where the NH groups and the OH group of the squaramide would coordinate to the nitroalkene 3 through hydrogen-bonding interactions with the nitro group. Simultaneously, the amine in the cinchona alkaloid would

(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

• stereochemistry of the carbon bearing the R2 group. Very recently, Wang and co-workers used a cinchona alkaloid-based bifunctional thiourea 103 as the catalyst of choice to an organocatalytic domino process. This domino reaction involded a Michael cyclization–tautomerization reaction sequence between isatylidene

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• their derivatives in asymmetric organocatalysis over the last five years or so [13][14]. The review is organized by reaction type, beginning with the Morita–Baylis–Hillman process – one of the first reactions to utilize 6’-OH-cinchona alkaloid derivatives in asymmetric organocatalysis. The focus will

• produced, as is often the case with cinchona alkaloid catalyzed processes. However, the role of the 6’-OH was clearly important when directly compared with the equivalent 6’-OiPr catalysts 66 and 68 (Scheme 16). Jørgensen and co-workers have used another anthracenyl-modified hydrocupreidine HCPD-70 in an

• with cupreine, cupreidine, β-isoquinidine and β-isocupreidine derivatives. The original 6’-OH cinchona alkaloid organocatalytic MBH process, showing how the free 6’-OH is essential for coordination to the substrate. Use of β-ICPD in an aza-MBH reaction. (a) The isatin motif is a common feature for MBH