Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• -DNA by terminal stacking. Keywords: berberine alkaloids; Cu-mediated coupling reactions; DNA recognition; nucleic acids; quadruplex DNA; Introduction Berberine (1a) is the most prominent member of the protoberberine family, i.e., a group of tetracyclic isoquinolinium alkaloids [1]. Like many members

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• -aminopyrroloquinolines with various biological activities. Keywords: 2-azahexatiriene system; carbodiimide; electrocyclization; pyrrolo[2,3-c]quinoline; trigonoine B; Introduction In 2011, two novel alkaloids, namely trigonoine A and B, were isolated from the leaves of Trigonostemon lii by Hao and co-workers [1]. The

• rearranged from a β-carboline skeleton (Figure 1). Additionally, the antihepatitis B virus (HBV) activity of the alkaloids was evaluated in vitro using an HBV-transfected HepG2 cell line. The antihuman immunodeficiency virus (HIV) properties were also investigated to determine whether trigonoine A and B

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• ] are central fragments in various natural products, which are often synthesized from lactams by reduction. This makes them important building blocks in the total syntheses of alkaloids and their non-natural analogs [17][18][19][20][21]. However, the γ-lactam substructure itself is a central fragment of

• numerous bioactive alkaloids, such as pyrrocidine B (I) [22], fusarin C (II) [23], fusarisetin A (III) [24], pseurotin A (IV) [25], (−)-salinosporamide A (V) [26], parvistemoline (VI) [27], glochidine (VII) [28], and other alkaloids [29][30][31][32][33][34] (Figure 1). Moreover, functionalized synthetic γ

• /EtOAc 10:1 to 1:1) to give keto lactam 13. Selected alkaloids containing the pyrrolidone motif. X-ray crystal structure of the major (2R,4S)-alkoxyamine hydrochloride derived from 9j. Displacement ellipsoids at 30% probability level and a disordered CHCl3 solvent molecule is not shown for clarity. X-ray

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• %) catalyst loading. Selected enantiomerically enriched sulfa-Michael addition products were subjected to oxidation to obtain the corresponding sulfones. Keywords: asymmetric synthesis; bifunctional catalysis; cinchona alkaloids; organocatalysis; sulfa-Michael reaction; Introduction Derivatives of the

• naturally occurring cinchona alkaloids have shown remarkable performance as organocatalysts for stereoselective synthesis in the past decade [1][2][3][4][5][6]. Among them, quinine-derived organocatalysts make a noteworthy appearance in the formation of new stereogenic centres, which can serve as valuable

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• pyrrolizidines; cyanoketones; legonmycin; vinylogous ureas; Introduction At least 40 members of the large class of pyrrolizidine alkaloids [1][2][3][4] have so far been characterized from bacterial cultures. Of these ‘bacterial pyrrolizidines’, those of the vinylogous urea type are particularly intriguing from

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• , West Common, Harpenden, AL5 2JQ, United Kingdon 10.3762/bjoc.17.4 Abstract The 9-azabicyclo[3.3.1]nonane ring system is present in several insect- and plant-derived alkaloids. (−)-Adaline (1) and (+)-euphococcinine (2), found in secretions of Coccinelid beetles, and (+)-N-methyleuphococcinine (3

• ), isolated from the Colorado blue spruce Picea pungens, are members of this alkaloid family. Their unique bicyclic system with a quaternary stereocenter, and the potent biological activity exerted by these homotropane alkaloids, make them attractive synthetic targets. This work aims briefly to review the

• variety of defensive alkaloids that makes them unpleasant for various predators [1]. Over 50 alkaloids have been characterized from ladybirds until now, including perhydroazaphenalenes, aliphatic and aromatic amines, piperidines, pyrrolidines, azamacrolides, dimeric alkaloids and homotropanes [2]. The

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• cycle by reacting with phosphine catalyst A to give H and C. Some total syntheses of hexacyclic Daphniphyllum alkaloids were reported by Li’s group (longeracinphyllin A (10) [41] and daphenylline (11) [42]) and Zhai’s group (daphenylline (11) [43]), applying Lu’s [3 + 2] cycloaddition (Scheme 6). The

• -workers used a platinum-catalyzed intramolecular [3 + 2] cycloaddition of a propargylic ketal derivative to complete the total synthesis of Kopsia indole alkaloids [67] (Scheme 11). The platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 afforded indoline 143 in 58

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• ]pyridines; nitroalkanes; polyphosphoric acid; Introduction It is hard to overstate the importance of imidazo[1,5-a]pyridines in modern organic and medicinal chemistry. Several natural alkaloids possessing this core were isolated from marine sponges, for example, cribrostatin 6 (Figure 1) [1][2][3]. The

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• activity in organic reactions. Tricyclic indole alkaloids bearing 3,4-fused seven-membered rings have attracted much attention because of their interesting molecular architectures and important biological activities [32][33]. Here the three-component reaction of 4-aminoindole (1a), 4-methylbenzaldehyde (2a

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• not provide evidence for a significant effect of the adenine unit on the binding affinity of the ligands, for example, by additional association with the loops, presumably because the adenine residue is sterically shielded by the neighboring triazole unit. Keywords: berberine alkaloids; DNA ligands

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• (Nymphalidae: Danainae) have hairpencils on the forewings (i.e., androconia) that disseminate semiochemicals during courtship. While most ithomiines are known to contain derivatives of pyrrolizidine alkaloids, dihydropyrrolizines, or γ-lactones in these androconia, here we report on a new class of fatty acid

• spectrometry; mimicry; pheromones; pyrrolizidine alkaloids; Introduction The Neotropical butterfly tribe Ithomiini (Nymphalidae: Danainae) is very diverse and species-rich, with over 390 species and 50 genera [1][2] and extensively involved in Müllerian mimetic interactions [3]. Ithomiines are well suited for

• , possess scent glands on their forewings, so-called androconia, covered with erectable hairpencils (Figure 1). They are used during courtship and are known to contain compounds acting as pheromones for the butterflies [2]. Adult ithomiines sequester pyrrolizidine alkaloids (PAs) pharmacophagously from

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• existing alkaloids and a number of pharmaceutically active compounds [51][52][53]. 2-Aminothiazole has a thiourea-like character with a tendency to modulate promiscuously multiple biological targets. Thiazole derivatives also exhibit a broad spectrum of biological activities including antiviral, antiprion

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• alkaloid-promoted electrophilic fluorination producing enantioenriched post-Ugi adducts fluorinated at the peptidyl position. Keywords: cinchona alkaloids; electrophilic fluorination; enantioselective synthesis; 2-oxo-aldehydes; Ugi reaction; Introduction Multicomponent reactions (MCRs) [1][2][3][4][5][6

• fluorinations with QD and DHQD led to the reversed stereoselectivity as compared to the reactions with Q and DHQ. For the benzylamine-derived substrates 8a–c benzyl ether derivatives of cinchona alkaloids favored the formation of the same enantiomer of 12 as their free alcohol counterparts (e.g., both Q-Bn and

• Q favored the formation of the same enantiomer of 12). In contrast, for the substrates 8d–g derived from aromatic amines a reversed trend was observed. In case of 8d–g, benzyl ether derivatives of cinchona alkaloids favored the formation of the opposite enantiomer of 12 as compared to the one

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• biologically active alkaloids. Proposed reaction mechanism. Fluorescence spectra of 2aA–nA, 2bB, 2hB, and 6C. Fluorescence spectra of 4aA–gA, and 4eB. Synthesis of β-carboline-linked 2-nitrochalcones. Synthesis of β-carboline-linked benzothiophenone frameworks. Comparison of outcome of one-pot vs two-pot

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• ], antiprotozoal [47], antidiabetic [48], and antitubercular [49]. Relevant is the role of the hydrazone moiety as antitumor agent [50][51][52][53]. An interesting example reported by Ferreira demonstrates that the chemical derivatization of the indole alkaloids dregamine and tabernaemontanine to yield new

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• in the host organisms. Keywords: antioxidant; Burkholderia sp; quinolone; soil bacterium; Zn2+ enrichment culture; Findings 4-Hydroxy-2(1H)-quinolone (3) is a unique structural motif mostly found in alkaloids from rutaceous plants (family Rutaceae) [1][2]. This motif has several tautomeric forms

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• photocatalyzed reduction of acyloximes 14.1a,b offered a smooth entry to iminyl radicals (Scheme 14) [76]. The process took place at room temperature and involved the cleavage of a C–O bond, followed by a cyclization to give access to the benzo[c]phenanthridine alkaloids noravicine (14.2a) and nornitidine (14.2b

• heteroarylalkynes. Synthesis of noravicine (14.2a) and nornitidine (14.2b) alkaloids. Gram-scale synthesis of the alkaloid trisphaeridine (15.3). Synthesis of phenanthridines starting from vinyl azides. Synthesis of pyrido[4,3,2-gh]phenanthridines 17.5a–d through the radical trifluoromethylthiolation of N-(o

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• heterocycle is present in several alkaloids such as emetine (1) and related compounds, that exhibit biological activities such as glucosidase inhibition, anti-amoebic properties as well as activity against breast cancer cell lines [2]. Notable examples of synthetic compounds include the dipeptidyl peptidase

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• into pyridoisoindolones 337 [94] (Scheme 65). To synthesize various pyrrolizidine alkaloids, Padwa’s group used the intramolecular photocycloaddition of N-but-3-enyl-5-thiopyrrolidin-2-ones 338. The intramolecular photo [2 + 2] cycloadditions first generated the tricyclic thietanes 339, which further

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• simplest pyrrole-fused heterocyclic aza-bridged compounds. The numerous series of pyrrolizine-containing polycycles include pyrrolo[2,1-a]isoindoles [6], pyrrolo[1,2-a]indoles [7][8][9][10] and isoindolo[2,1-a]indoles [11] (Figure 1). These three series constitute the core of natural occurring alkaloids

• natural pyrrolizine- and isoindole-containing alkaloids. Structures of 9m (a) and 10m (b) as determined by single-crystal X-ray diffraction crystallography (ellipsoids at the 30% probability level). M06-2X/6-31+G(d,p) Optimized geometry for each of the SCs (a and d), TSs (b and e) and ADs (c and f) of the

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• crispine A isolated from Carduus crispus L has antitumor activity [3]. Erythrina alkaloids have curare-like neuromuscular blocking activities [4], and also antioxidant activity against DPPH free radicals [5]. Lamellarins isolated from marine invertebrates [6] are inhibitors for HIV-1 integrase and also

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• ). Ferroud’s group showed that the α-photocyanation of amines can be efficiently applied in complex molecules. The authors reported a highly regio- and diastereoselective photocyanation of both catharanthine and 16-O-acetylvindoline alkaloids with TMSCN and using TPP as photocatalyst (Scheme 58) [106][107

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• the cis-disubstituted double bond in the latter was performed under a high pressure of hydrogen, leading to the saturated tricyclic scaffold that was used as a key intermediate in the total synthesis of lycoflexine (15, Scheme 18). Manzamine alkaloids A highly interesting application of a metathesis

• reaction for accessing bioactive organic molecules is found in the complex synthesis of manzamine alkaloids. These efficient antitumor agents, originally isolated from several genera of marine sponges, contain a pentacyclic core with a pendant β-carboline moiety. Their total synthesis implies an elaborate

• . Securinega alkaloids The total synthesis of the Securinega alkaloids, (−)-flueggine A (18) and (+)-virosaine B (19), which are potent anticancer agents, was proposed by Wei et al. [90] via a relay ring-closing metathesis (RRCM) associated with a 1,3-dipolar cycloaddition. The enyne precursors bearing a

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• moderate to good yields, and the functional group tolerance was excellent. Later in 2018, Evano and co-workers used their methodology to reduce aryl iodide for the synthesis of the alkaloids rosettacin, luotonin A, and deoxyvasicinone (Scheme 22) [37]. The developed strategy relied on the addition of an

• aryl radical on ynamides or cyanamides, followed by a final cyclization. Using similar reaction conditions as those used for the Meerwein arylation, the three alkaloids were synthesized in good to excellent yield in a straightforward manner. In 2017, Fu, Peters, and co-workers reported the copper

• and 5-exo-trig cyclization catalyzed by the photocatalyst [Cu(I)(bcp)(DPEPhos)]PF6. a5 mol % of catalyst and 5 equiv of DIPEA were used. [Cu(I)(bcp)(DPEPhos)]PF6-photocatalyzed synthesis of alkaloids. aYield over two steps (cyclization and TMS deprotection). Copper-photocatalyzed decarboxylative