Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• . A compound which was found to be predominantly produced under iron deficiency was subsequently isolated. Its structural characterization by spectroscopic and bioinformatic analyses revealed a previously not known diastereomer of the cytotoxic alkaloid agrochelin. The structure of this natural

• atoms. In this way, the full planar structure of 1 was elucidated. According to a literature search, 1 possesses the same chemical constitution as the alkaloid agrochelin (2, Figure 2), which was previously reported from a marine bacterium of the genus Agrobacterium [18]. However, we also noted some

• S3, Supporting Information File 1). Conclusion In summary, Massilia sp. NR 4-1 was found to synthesize an epimer of the alkaloid agrochelin under iron-deficient conditions. The structure of massiliachelin is consistent with the architecture of a biosynthetic assembly line, which is encoded in the

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

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

• 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

• ) the cinchona alkaloid moiety can be successfully attached to CD scaffolds through a CuAAC reaction, (ii) the permethylated cinchona alkaloid–CD catalysts showed better results than the non-methylated CDs analogues in the AAA reaction, (iii) promising enantiomeric excesses are achieved, and (iv) the

• catalysts, a disubstituted α-CD derivative as a pure AD regioisomer with two identical cinchona alkaloid residues was prepared and tested in the AAA reaction. Our study shows that the CuAAC reaction is a good and high-yielding method for the functionalization of the CD skeleton when attaching sterically

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• and vinyl azides 92 for the synthesis of azaheterocyles 93 (Scheme 20) [98]. This strategy could also be applied to the synthesis of the quaternary indole alkaloid and melinonine-E. Quinones play an important role in organic chemistry because of their unique structure. In 2013, Malayappasamy and co

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• of the alkaloid hemerocallisamine skeleton [37], its tert-butyl counterpart was used as a starting material in a multistep synthesis of a functionalized exo-methylenecyclopentane skeleton as an entecavir intermediate [116]. On the other hand, the stereospecific alkylation of methyl (2R,4R)-4

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

• and six-membered carbocyclic ring system can be achieved in only four steps from a simple acyclic β-keto ester. Keywords: alkaloid; Danheiser annulation; decahydroquinoline; Introduction cis-Fused hydrindanes (bicyclo[4.3.0]nonanes) [1][2], scaffolds of numerous natural products, are amenable to

• not relevant for the potential application of this type of building block (i.e., 8) in fawcettimine and related alkaloid synthesis, since this stereogenic center is epimerizable, as shown by Heathcock [7]. Conclusion In summary, we have successfully applied the Danheiser annulation reaction to rapidly

• hydrindan-2,4-diones. Stereoview of cis-hydrindane 8. Decahydroquinoline 1 as a versatile building block for Lycopodium alkaloid synthesis. A de novo approach to 3a-substituted cis-hydrindan-2,4-diones. Synthesis of enone 4 and the Danheiser annulation. The depicted compounds are all racemic. Transformation

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

• ), aknadilactam (2), and the known morphinane alkaloid sinococuline (3), which was identified as a bioactive component from S. japonica [7]. In 1963 Brown et al. isolated 1-acetyl-aspidoalbidine (4) from Vallesia dichtoma [8] and subsequently, Djerassi proposed its structure [9]. Another alkaloid

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• pharmacological interest. For example, vasicine is a 3,4-dihydroquinazoline alkaloid isolated from natural sources with antitumor activity [1]. Vasicine and deoxyvasicine are also potent butyrylcholinesterase (BChE) inhibitors [2]. Some synthetic derivatives containing the dihydroquinazoline scaffold have shown

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• ]quinazolines were synthesized and exhibited good antimicrobial as well as notable antifungal activities [9][10][11]. Since the isolation of hinckdentine A, an unusual marine alkaloid from the bryozoan Hincksinoflustra denticulata collected off the eastern coast of Tasmania [12][13], indolo[1,2-c]quinazolines

A novel and practical asymmetric synthesis of eptazocine hydrobromide

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

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• and methallyl iodide [10]. However, these methods were undermined by expensive reagents, poor yields, harsh reaction conditions, or complex synthetic procedures. Phase-transfer asymmetric catalysis using cinchona alkaloid-derived quaternary ammonium salts is a practical method in organic synthesis [11

• alkaloid-derived catalysts was identified as the best one for asymmetric alkylation of 1-methyl-7-methoxy-2-tetralone (2) with 1,5-dibromopentane. The products I-13a and I-13b were isolated in a ratio of 79:21 and in 77.8% yield (Scheme 2). Encouraged by the previous studies and relevant works [15][16], we

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• steps in the pyrrolidine pathway. This review summarizes the present status of our understanding of these pathways, focusing on what is known about the individual enzymes involved. Keywords: biodegradation; enzyme mechanism; flavoprotein; metabolic pathway; nicotine; Introduction The toxic alkaloid (S

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

• experiments of P and B with 2,2’-CBP4 in deuterated phosphate buffer (pD 7.4) were carried out to examine the host–guest complexation (Figure 1 and Figure S9 in Supporting Information File 1). From Figure 1, upon addition of the host, all the peaks of alkaloid B displayed upfield shifts and broadening

• was included by 2,2’-CBP4; the guest emits stronger fluorescence in a more hydrophobic microenvironment [48]. Combined with NMR results, we can unambiguously conclude the alkaloid molecules must insert into the hydrophobic cavity of 2,2’-CBP4 to form inclusion complexes. Interestingly, the emission

• ’-CBP4, for the first time and studied its complexation towards two alkaloid guests, P and B. 1H NMR and fluorescence results indicate the formation of inclusion complexes with strong stability. The association constants are in the magnitude of 105–106 M−1. Upon complexation with 2,2’-CBP4, both alkaloid

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• , indolizidines etc. which exhibited remarkable biological activities and are highly interesting as pharmaceutical agents [15][16][17][18][19]. In addition, iminosugars exhibited a powerful inhibitory activity against a wide range of glycoside hydrolases [20][21][22]. One naturally occurring iminosugar, alkaloid

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

• drugs for the treatment of several health problems [9][10]. Annosqualine (1) is an isoquinoline-cored alkaloid and it was isolated in 2004 from the stem of Annona squamosa [11] (Figure 1). Griseofulvin (2) is a spirobenzofuranone-based naturally occurring compound which was isolated from Penicillium

• griseofulvum in 1939 [12]. In 1959, it was launched in the market as antifungal agent for the treatment of ringworm in human beings and animals [4][13]. Stepharine (3) is a member of the proaporphine alkaloid family and isolated from an angiosperm Stephania glabra [14]. Tofogliflozin (4) is a synthetic

• synthesis In 2005, Wipf and Spencer [79] reported the first total synthesis of the Stemona alkaloid (−)-tuberostemonine (40). In this report, PIDA (15) was used as an electrophile for the synthesis of spirolactone 16 in 35% yield by the cyclization of L-tyrosine 14 in nitromethane at room temperature for

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

• 10.3762/bjoc.14.119 Abstract In order to prepare asymmetrically (R)-(+)-1-(5-bromopentyl)-1-methyl-7-methoxy-2-tetralone (3a), a key intermediate of dezocine, 17 cinchona alkaloid-derived catalysts were prepared and screened for the enantioselective alkylation of 1-methyl-7-methoxy-2-tetralone with 1,5

• separated by two times of resolution with L-tartaric acid and D-tartaric acid (Scheme 1). Phase-transfer asymmetric catalysis with cinchona alkaloid-derived quaternary ammonium compounds has become one of the topics in stereoselective synthesis in both industry and academia [6][7][8][9]. It was reported [10

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

• ]. An extensively used two-component variant of this reaction consists in using a preformed imine. Among chiral metal complexes, a wide variety of organocatalysts [26][27][28][29][30][31][32][33][34] has been used to promote asymmetric Mannich reactions. Among them, cinchona alkaloid 1 was employed in

• -dicarbonyl compounds 5 performed in the presence of chiral cinchona alkaloid-derived squaramide 6 [36]. A range of chiral 3-amino-2-oxindoles 7 was obtained under mild reaction conditions in high to quantitative yields (78–99%) and uniformly excellent enantioselectivities (90–99% ee) as shown in Scheme 2. In

• diastereoselectivity of 90% de was achieved in the reaction of 1-benzoylacetone (R2 = Me, R3 = Ph) which afforded the corresponding single diastereoisomeric product in 96% yield and 95% ee. In 2018, Tanyeli et al. reinvestigated this type of reactions in the presence of related cinchona alkaloid-derived squaramide

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• research group. Docking and modelling of cryptophycin derivatives There is no X-ray analysis of cryptophycin–tubulin complexes available to provide information on the binding site. Based on biochemical evidence, binding close to the vinca-alkaloid binding site of β-tubulin, the so called “peptide-site

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• -pyridinone ring is present in milrinone (1), used to treat heart failure, while a 4-pyridinone is part of mimosine (2), an alkaloid isolated from Mimosa pudica. A benzene-fused pyridinone – a quinolone – can be found in brexpiprazole (3), a drug used against schizophrenia. In addition, the indole core is

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• system (Scheme 1). Their dipolar resonance structures such as tropylium oxide form 1B and 2B have been reported to provide a Hückel sextet of electrons that is necessary for aromaticity (Scheme 1) [1][2][3][4][5][6][7][8][9]. The tropone core is the ubiquitous structural motif in the alkaloid colchicine

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

• as a result of binding to minor groove DNA. Samanta et al. investigated a thorough structure–activity correlation between mahanine, an anticancer carbazole alkaloid, and its chemically modified analogs to test the role of various functional groups on its antiproliferative activity against 19 cancer

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

• of other types of cancers (breast cancer, bladder cancer, Kaposi's sarcoma) in combination with other anti-cancer agents. Camptothecin (CPT): Camptothecin is a cytotoxic alkaloid collected from extraction of the bark and stem of the Chinese tree ‘Camptotheca acuminata’. It was first isolated and

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

• unexpected side products. As mentioned above [71], Osyanin et al. reported the synthesis of Uvaria scheffleri alkaloid (±)-schefflone. In this publication, the dimerization of the o-QM resulting in intermediate 41 is a key step in the synthesis of the final natural trimer compound. Reactions with C=N

• polyheterocycles formed was also described. The [4 + 2] cycloadditions between cyclic imines and o-QMs derived from Mannich bases could also be successfully applied in the syntheses of natural alkaloid-like compounds 47. Osyanin et al. reported the preparation of rutaecarpine and evodiamine, the 14-oxa analogues

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

• products and in drug development and hence, effective synthetic approaches are required. Here we present a novel method for the introduction of a methyl group at C1 of isoquinolines. This is exemplified by a new total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline. Direct metalation of

• 7-benzyloxy-6-methoxyisoquinoline with Knochel–Hauser base, followed by cuprate-mediated methylation gives the target alkaloid directly, but separation from the educt is cumbersome. Quenching the metalated intermediate with Eschenmoser’s reagent gives an easy to clean tertiary benzylamine, which

• , after quaternization with iodomethane, is easily converted into the desired 1-methylisoquinoline by hydrogenolysis of both the benzylamine and benzyl ether groups. Keywords: alkaloid; aminomethylation; hydrogenolysis; isoquinoline; metalation; methylation; Introduction The isoquinoline ring system has

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• chemistry; heterocycle; hydrogenation; indole; multistep; Introduction Indoles are amongst the most important bioactive heterocyclic structures being commonly encountered in the amino acid tryptophan (1), the related neurotransmitter serotonin (2) as well as numerous complex alkaloid natural products and