The role of spacer length and flexibility in peptide self-assembly

• Julian Link,
• Albin Lahu,
• Manfred Wagner,
• Tanja Weil and
• David Y. W. Ng

Beilstein J. Org. Chem. 2026, 22, 986–996, doi:10.3762/bjoc.22.77

• synthesize the Cx-spacers, the anhydride was transformed into the imides by refluxing the corresponding amines with the anhydride in the presence of a catalytic amount of 4-(dimethylamino)pyridine (4-DMAP). Through reaction of 2 with 6-aminohexanoic acid, 6-(1,3-dioxo-6-(piperidin-1-yl)-1H-benzo[de

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• with an increased catalyst loading of 20 mol %. The reaction affords lactams in up to 83% yield using amides containing various functional groups and substituted 1-bromo-2-iodobenzenes. Furthermore, 1,2-dibromo heteroarenes, such as benzothiophene and pyridine, undergo annulation to give the

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• -methylpyrrole-2-carbaldehyde and 4-hydroxybenzaldehyde, likely due to a shift in equilibrium toward the starting compounds. The reaction with strongly electrophilic, acceptor-substituted aromatic aldehydes, 4-nitro-, 4-cyanobenzaldehydes, and pyridine-4-carbaldehyde, is accompanied by complete resinification of

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• trialkylphosphines, anionic carbon and hydride ligands. N- and O-lone pair donors (pyridine, water) are weak ligands. The following indicative series is typical for Pt(II), although there may be slight variations in the specific ordering depending on the complex type under investigation: CO, CN−, C2H4 > P(alkyl)3

• , while C^N^C and C^C^N ligand frameworks look like simple structural isomers, their reactivity and analysis of their bonding has shown that replacing the weak N(pyridine) donor by strongly donating anionic carbon leads to profound changes in gold orbital ordering, often with drastic consequences for

• ^C^C(carbene) alkynyl complexes are similarly strongly emissive [43]. Since the π–π* gap of pyrazine is 0.95 eV smaller than that of pyridine, it is a much better electron acceptor, and pyrazine-based complexes of type B (X = Cl, -C≡CPh) show intense emissions. Since the non-coordinating N atom in

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• 1,8-diazafluorene (2) was performed using a TiCl4/pyridine system. However, the reaction yield was very low (11%) [15]. The latter approach was also used [22] for the condensation of 4,5-diazafluorene with ketones being especially challenging due to sterical issues. Moreover, this approach requires

• the smelly solvent pyridine, moisture-sensitive environmentally aggressive reagent (TiCl4) and subsequent complicated treatment of the resulting reaction mixture making it inapplicable for large-scale high-efficiency production of functional materials. Therefore, analyzing the literature examples we

• condensation using TiCl4 and pyridine, is cheaper, easier to apply, and the pure target product simply precipitated from the reaction mixture instead of extraction and purification by column chromatography. Di(pyridin-2-yl)methylene)-9H-diazafluorenes Furthermore, since ketones are generally considered to be

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• ]pyridine-2-carbaldehydes is reported. A Groebke–Blackburn–Bienaymé reaction between 2-aminopyridine derivatives, cyclohexyl isocyanide and glyoxylic acid in the presence of methanol and an acid catalyst gave the 2-ester derivatives that were reduced to give the corresponding alcohols. Mild Kornblum

• -chloroaniline. Alternative oxidation conditions such as PCC, IBX or T. versicolor laccase applied to the alcohols led only to oxidative ring-opening to give oxalamide derivatives, with no aldehyde being isolated. Keywords: 3-aminoimidazo[1,2-a]pyridine-2-carbaldehydes; Groebke–Blackburn–Bienaymé reaction

• ; Kornblum oxidation; oxidative ring-opening; reductive amination; Introduction Imidazo[1,2-a]pyridines display a wide range of different biological activities, and this scaffold has come to be regarded as being biologically privileged [1]. Compounds containing the imidazo[1,2-a]pyridine core have been

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• heteroaryl substituents; various β-aryl- and alkyl-substituted alkenyl heteroarenes, such as benzoxazole, benzothiazole, 1-methyl-1H-benzo[d]imidazole, dihydrooxazole, and isoquinoline, as well as monocyclic heteroarenes, including oxazole, thiazole, imidazole, pyridine, and pyrazine, can be used as

• activated alkenes was proposed. The authors demonstrated the potential for cycloaddition of silylimines containing a pyridine substituent with various dipolarophiles (Scheme 33). In all cases, the cycloaddition reactions proceeded with very high diastereoselectivity (trans/cis >95:<5), providing the trans

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• ; HRESIMS m/z: [M + Na]+ calcd for C20H2079Br2NaO6, 536.9519; found, 536.9519 [25]. Acylation of (+)-pinoresinol (2) (+)-Pinoresinol (2, 13.4 mg, 0.037 mmol) was dissolved in pyridine-d5 (200 μL) before 3,3-dimethylbutyryl chloride (150 μL) was added dropwise. The reaction mixture was stirred for 1 h at

• , tR 48−50 min, 70% yield). (+)-Pinoresinol (2, 8.0 mg, 0.022 mmol) was dissolved in pyridine-d5 (200 μL) before pivaloyl chloride (100 μL) was added dropwise. The reaction mixture was stirred for 1 h at room temperature and purified using the same method described above to give (+)-4,4

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• presence of a base in acetonitrile (Scheme 1a) [14]. Stephenson and colleagues subsequently demonstrated the use of trifluoroacetic anhydride (TFAA) with a Ru-based photocatalyst in acetonitrile, employing pyridine-N-oxide as an additive (Scheme 1b) [15]. More recently, the Pan group developed a protocol

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• pyridine ring and carboxyl group [6][7][8][9]. On the other hand, the sulfonamide and sulfone groups are commonly found in the design of potential therapeutics with various types of biological activities, such as antimicrobial, antitubercular, antileishmanial, antiviral, anticancer, antidiabetic, anti

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• ) in pyridine and 4-(dimethylamino)pyridine (DMAP) in 95% yield. Treatment of azido nitrobenzoate 8 with m-CPBA gave a mixture of isomeric epoxides 9a and 9b with a combined yield of 97%. The formation and ratio of these isomers were determined by NMR spectroscopy, showing a 63:37 ratio (1H NMR) of 9a

• NMR (100 MHz, CDCl3) δ 130.3, 127.5, 73.1, 66.8, 32.4, 29.7, 23.5, 23.1. (1S*,8S*,Z)-8-Azidocyclooct-4-en-1-yl 4-nitrobenzoate (8) The azidol 7 (0.50 g, 2.99 mmol) was dissolved in 9 mL of anhydrous pyridine and the solution was cooled to 0 °C. p-Nitrobenzoyl chloride (1.11 g, 5.98 mmol) and 4

• -(dimethylamino)pyridine (DMAP, 2 mg) were added and the mixture was stirred at room temperature for 24 hours. Then, the solution was cooled to 0 °C and 100 mL of 2 M HCl added and stirred for 5 min. The mixture was extracted with ethyl acetate (4 × 30 mL). The organic phase was washed with saturated NaHCO3 (2

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• -position in regard to the OH-group at C-10b (Table 2). Synthesis of melifoliones Melifolione A (1) was prepared according to the method of Wang and Lee [5] by heating phloroacetophenone and citral with ethylene-diammonium diacetate (EDDA) in DMF. However, reaction of the educts in pyridine at 60 °C led to

• -trihydroxyacetophenone (3.7 g, 20 mmol), citral (3.2 g, 21 mmol) and pyridine (1.6 g, 20 mmol) was heated with stirring in a water bath at max. 60 °C for 8 h. After cooling to room temperature, the reaction mixture was diluted with 200 mL diethyl ether and extracted with 0.1 N H2SO4 (3 × 20 mL) to remove the pyridine

• compound 11. Structures of isomeric melifoliones and corresponding oxidation products. Structure of iodized melifoliones. Left Part: 11 (main fraction); Right part: 12 (side product). Synthesis of melifoliones and by-products: a) pyridine/60 °C/8 h/51%, b) microwave/140 °C/20 min/70%, c) acetic acid/80 °C

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• °C; (b) Pd(PPh3)4, PPh3, HCOOH, NEt3, THF, 60 °C; (c) i. Mg(OMe)2, THF, MeOH, rt; ii. TBDMSCl, imidazole, DMF, rt. Below: Mechanism of the allene-Prins reaction. Synthesis of 64. Reaction conditions: (a) i. acetone, I2, rt; ii. vinylmagnesium bromide, THF, −20 °C to rt; iii. TsCl, pyridine, 65 °C; (b

• , pyridine, DMAP, DCM, rt; iii. allyl-TMS, BF3·Et2O, DCM, −78 °C; (h) 9-BBN, THF, H2O2, 0 °C to rt; (i) i. AD-mix β, MsNH2, t-BuOH, H2O, rt; ii. 2,2-dimethoxypropane, (±)-CSA, DCM, rt; (j) i. DMP, DCM, rt; ii. Ph3PCH2COOEt, toluene, rt; (k) p-TsOH, EtOH, reflux; (l) i. DBU, toluene, reflux; ii. TBAF, THF, rt

• . AcOH, H2O, rt; ii. NBS, NaHCO3, NaOAc, THF, H2O, 0 °C; iii. acetic anhydride, pyridine, DCM, 0 °C; (e) i. allyl-TMS, BF3·OEt2, MeCN, −10 °C; ii. DDQ, DCM, H2O; (f) i. DMP, NaHCO3, DCM, rt; ii. NaBH4, DCM, MeOH, −78 °C; iii. Stryker’s reagent, toluene, rt; iv. (±)-CSA, MeOH, 60 °C; (g) acetic anhydride

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• in the synthetic route. Therefore, the reaction conditions of 2 and a selected benzaldehyde 3a with two MOM-protected OH groups were optimized. Firstly, various organic and inorganic bases were screened (Table 1). The commonly used organic bases, such as Et3N, DBU, and pyridine, seemed not effective

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• -glucamine). Compounds II were obtained by the sequence of reactions starting from available 2-aryl-4-dichloromethylene-1,3-oxazol-5(4H)-ones I [18]. Thus, treatment of compounds I with arylamidine hydrochlorides in the presence of triethylamine, followed by heating with pyridine, afforded the

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• ]helicene VII via cycloborylation of a pyridine-substituted carbo[6]helicene [41], while Xu, Wang and colleagues reported a multistep route to azabora[8]helicene VIII (Scheme 1B) [42]. Collectively, these studies highlight both the synthetic bottleneck and the untapped potential of unsymmetrical hetero[8

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• electrophilic addition. Comparable effects are observed for furans and pyridines, where η2-coordination accentuates their vinyl ether and imine character, respectively. As an illustrative example, treatment of the phenol complex 5 with methyl vinyl ketone and pyridine affords 4-alkylated 4H-phenol complex 6 as

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• with α,β-unsaturated esters, such as (E)-3-(3,4-dimethoxyphenyl)acrylic acid esters 3 (see Supporting Information File 1) exemplified by compound 4. Different solvents and catalysts, both acidic and basic, were screened at room temperature, including refluxing in pyridine with piperidine, but the

• -unsaturated malonate 6 with 2a–c, various bases (sodium methoxide, triethylamine, potassium hydroxide) and solvents (ethanol, DMF, pyridine) were tested, mostly at room temperature, with an additional attempt at refluxing in ethanol/DMF. The desired malonate Michael adduct 7 (isolated and fully characterized

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• )phosphide anion [P(SiCl3)2]−, can be converted into a variety of phosphorus compounds, including P(III) species, demonstrating the potential to reduce reliance on white phosphorus (Figure 2B) [42][43]. In addition, Weigand’s group reported a method using Tf2O and pyridine to convert P(V) compounds such as

• phosphoric acid and condensed phosphoric acid into a versatile PO2+ phosphorylation agent, (pyridine)2PO2[OTf]. The intermediate reacts with a variety of nucleophiles, providing a redox-neutral method for the flexible synthesis of P(V) compounds (Figure 2C) [44]. Furthermore, Naganawa’s group recently

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• Mannich reaction between a 2-sulfonylpyridine protected imine and a malonate (Scheme 1). The pyridine-containing protecting group was chosen considering our catalyst design. We envisioned that halogen bond (XB) will complement hydrogen bonds to activate an imine towards the nucleophilic attack of the

• , entry 17), further highlighting the importance of the pyridine ring containing protecting group. The interaction between catalyst E and the imine was further investigated by 19F NMR studies (see Supporting Information File 1). To further elucidate the role of noncovalent interactions, we conducted

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• , isoquinoline, pyridine, and related substrates can now be reduced with high efficiency and stereoselectivity, providing efficient access to saturated and partially saturated architectures vital to synthetic chemistry. Furthermore, catalytic asymmetric aromatic hydrogenation has facilitated the asymmetric total

• catalytic hydrogenation are relatively rare. This is partly due to the high stability of six-membered aromatic heterocycles, such as pyridine, making it difficult to interrupt the aromaticity under mild conditions [34]. Furthermore, the heteroatoms (such as nitrogen and oxygen atoms) within the saturated

• heterocycles exhibit strong Lewis basicity, potentially complexing and deactivating catalysts. Consequently, the catalytic hydrogenation of six-membered aromatic heterocycles such as pyridine often requires the introduction of substituents or activation of the aromatic heterocycle to facilitate hydrogenation

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• ]. They demonstrated that a 9:1 molar ratio of pyridine to PCl5 converts ketones to alkynes within minutes under microwave irradiation (not shown). High yields for alkenyl chlorides from ketones by reaction with PCl5 were reported under various conditions on preparative scales. For instance, a patent from

• alkenyl chlorides using triphosgene (BTC) (Scheme 21) [77]. In the presence of excess pyridine, BTC mediated the transformation of various ketones into the corresponding alkenyl chlorides, which were obtained in moderate isolated yields despite consistently high GC yields. The authors attributed this

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• promise for the three-component approach we have proposed. The importance of trifluoromethyl-containing pyridine and piperidine systems is well known for both medical and agrochemical applications [30]. Thus, many medicinal agents have such fragments, for example, the non-nucleoside reverse transcriptase

• inhibitor doravirine [31], calcitonin gene-related peptide (CGRP) antagonist ubrogepant [32], dipeptidyl peptidase-4 (DPP-4) inhibitor gemigliptin [33]. The trifluoromethyl pyridine framework is also widely used in the development of plant protection products [34], including the fungicides fluopicolide [35

• the one hand, owing to the fact that the pyridine framework is widespread among natural compounds [40][41], and, on the other hand, because of the unique properties of fluorine [42][43][44][45]. In this work, 1,3-diaminopropan-2-ol (3) has for the first time been introduced into the reaction of ethyl

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• ][18][19]. The earlier publications provide an access to the ABCD-skeleton with a C-nor-D-homo motif through a diol cleavage (Malaprade reaction) and intramolecular aldol reaction to furnish the five-membered C-ring. The F-ring is later attached, first as a pyridine, which then gets hydrogenated to a

• -methylpyridine was added to the intermediate to yield 82. Finally, the D-ring was aromatized, the pyridine ring hydrogenated, and after several protecting group manipulations, installation of the C5–C6 double bond and deprotection, verarine (14) was obtained. The reported synthesis of verarine has a total step

• transformed into rockogenin 12-methanesulfonate-3-pivalate (89) by reduction and mesylation. Heating to reflux in anhydrous pyridine afforded the rearrangement to the C-nor-D-homo isosteroid skeleton 90 with an exocyclic 13,18-double bond in 5 steps from hecogenin acetate (see Scheme 29). In a five-step

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• , reflux, 9 h; 2. SnCl4, 0–5 °C, 15 h, 86%; v) NaBH4, DMF, EtOH, rt, 3.5 h, 94%; (vi) SOCl2, DCM, rt, 2 h crude: 94%; vii) R1R2NH, dioxane or MeCN, rt, 1 h, 74–85%; viii) MeOH, DCM, rt, 40 min, 76%. Synthesis of tetracyclic compounds 54. Conditions: i) methyl anthranilate, pyridine, 0–5 °C, 4 h, rt, 13 h

• , 95%; ii) method A: MeI, K2CO3, DMF, rt, 22 h, crude: 99%; iii) method B: methyl N-methylanthranilate, pyridine, 0–5 °C, 2 h, rt, 17 h, 71%; iv) NaOH, MeOH/H2O, reflux, 1 h, crude: 95%; v) 1. SOCl2, DCM, reflux, 8.5 h; 2. AlCl3, 0–5 °C, 1.5 h, reflux, 3 h, 26%; vi) NaBH4, DMF/EtOH, rt, 2 h, 93%; vii