Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• ] using Co(II) catalyst 113, in the presence of PhSiH3, TsCl in MeOH resulted in the formation of a cyclopentenone derivative 111 with a yield of 43% and a small amount (<5%) of cyclopentenone derivative 112. The remaining mass balance consisted mainly of the recovered starting material. Demethylation of

• (±)-terretonin L (109) as the main product with a yield of 46%. Radical hydrochlorination of olefin 110 under more powerful oxidizing conditions (Co(II) catalyst 113, N-fluoropyridinium salt (F+) 114), resulted in the formation of cyclopentenone derivative 112 with a yield of 90%. Demethylation of the latter led

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• moderate diastereoselectivity; this was followed by Mn(III)-catalyzed metal-hydride hydrogen atom (MHAT) transfer to reduce the endocyclic olefin, forming 41 as a single diastereomer. Subsequent transformations – including a Wittig reaction, demethylation, and oxidation of the resulting phenol to a p

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• -catalyzed Suzuki cross-coupling reaction of sterically hindered substrates developed by Han [35][36][37], the coupled product 57 was obtained in a satisfactory yield (72%) from 55 and pinacol boronate 56, along with trace amounts of the double bond migrated side product 58 (57:58 = ca. 15:1). Demethylation

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• process, which further supported the probability of the proposed biosynthetic approach. Subsequently, site-selective methylation on phenol provided 24, which further underwent O-directed demethylation to afford (12S)-hydroxymonocerin. On the other hand, a two-step protocol involving Mitsunobu reaction

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• is the retrosynthetic analysis for the key intermediate 1, which can reach the final compound VI via chlorination and demethylation [19]. Target molecule 1 can be accessed by decarboxylation reaction from compound 13, prepared by an intramolecular Heck reaction between the β-ketoester and the vinyl

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• Suzuki coupling of β,β-dibromenones 100, boronic acids, and 1,1-dimethylhydrazine in a three-component reaction (Scheme 36) [119]. The intermediary 5-bromopyrazoles formed by condensation/N-demethylation/cyclization sequence subsequently react by Suzuki–Miyaura cross-coupling in a one-pot fashion. The

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• -rich enones 2o,t,u, bearing electron-donating substituents in the aromatic rings, afford complex mixtures of oligomeric materials. The cyclization of hydroxy ketone 1k into indanone 3k is accompanied by demethylation of one of the methoxy groups (Scheme 6). The positions of hydroxy and methoxy groups

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• benzofuran-2(3H)-one derivative 144 having an aza-quaternary stereocenter. The achiral Lewis acid tris(pentafluorophenyl)borane was required as additive in the reaction system to enhance the chemical yield and enantioselectivity. After two additional steps, i.e., demethylation of the phenolic ether and ester

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• (II)–alkenyl intermediate 88. Then, the intermediate 88 undergoes protio-depalladation and demethylation to yield the Z-isomer 85 (Scheme 17b). In case of N-benzylpyridinium salts 83, first debenzylation occurs to form 2-pyridyl–Cu(I) species 89 in the presence of CuBr which then coordinates to the Pd

• followed by transmetalation with CuI pyridyl species 133 generated from the reaction of Cu2O with the methylated pyridine to afford intermediate 134 that on reductive elimination results in salt 135. Subsequent demethylation of 135 gives monoarylated product 136 or the intermediate 135 reenters the

• catalytic cycle to produce the diarylated N-methylpyridinium species, which again undergoes demethylation to produce product 131. C-3 Arylation In 2011 and 2013, the groups Yu [95] and Tan [96], reported a ligand-assisted distal arylation selectively taking place at the meta-position in pyridine. Both

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• -terminated butadiyne 5 gradually underwent demethylation/acid-catalyzed heterocyclization involving one of the dimethylamino groups and the adjacent C≡C bond of the butadiyne linker, forming the corresponding benzo[g]indole derivative. Proton sponge-based 1,4-diaryl-1,3-butadiynes synthesized previously and

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• , the authors employed an Ullmann-type condensation [28] between ester 14 and 4-iodobenzaldehyde (15) to give the corresponding diaryl ether 16 in 78% yield. The subsequent demethylation reaction using boron triiodide also promoted the hydrolysis of the ester, and thus a re-esterification step was

• 97% yield. Subsequent intramolecular Ullmann-type reaction using CuMe under high dilution conditions [31] gave macrolide 28 in low yield. Finally, demethylation using boron triiodide [32] led to the formation of combretastatin D-2 (2, Scheme 5). Using this strategy, Boger succeeded to synthesize

• equiv) in PhMe led to the corresponding macrolide 28 in 20% yield. Since the demethylation step of 28 was known [27], the authors described a formal synthesis of combretastatin D-2 (2, Scheme 6). Despite the low yield, the authors managed to bypass the dimerization reaction previously reported by Boger

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• 23% overall yield. First, hydrolysis of 1, in situ conversion to the acyl chloride and subsequent Lewis acid-promoted Friedel–Crafts acylation reaction produced compound 2 (Scheme 1), where the AlCl3 was also responsible for the demethylation. Compound 2 was then subjected to monoalkylation with 1,4

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• lactone moiety and demethylation, respectively (Figure 4). Subsequent dehydration would afford compound 2 with an α,β-unsaturated carboxylic acid moiety. Alternatively, the ring opening of compound 4 and demethylation of compound 5 would occur prior to the oxa-Michael reaction. Accordingly, the absolute

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• . Review Preparation methods of menadione Among the most common methods for the preparation of menadione (10), we can find, for example, the oxidation of 2-methylnaphthalene or 2-methylnaphthol. Other less frequent but equally efficient approaches to synthesize menadione include the demethylation of 2

• bismuth(III) triflate. The use of tert-butyl hydroperoxide in the presence of bismuth(III) triflate for the methylation of 1,4-naphthoquinone (1) provided 10 in 43% yield, in already optimized conditions (Scheme 3). Demethylation of 2-methyl-1,4-dimethoxynaphthalene The oxidative demethylation of 1,4

• -dimethoxyarenes is another valid synthetic approach to achieve 1,4-quinones, with the oxidative demethylation of 2-methyl-1,4-dimethoxynaphthalene (19) can be used to synthesize menadione (10). The oxidizing agents most commonly used in oxidative demethylation are cerium(IV) ammonium nitrate (CAN), and silver(II

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• alcohol 192 was involved. The reaction went through the formation of a mixture of diastereoisomers 193a and 193b. After which the inseparable mixture of products underwent further oxidative demethylation and yielded the final products (Scheme 59) [120]. Kraus and co-workers had reported the synthesis of

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• trifluoroacetic anhydride (TFAA) in total 6 steps (Scheme 16a) [84]. Already used by Hartke in 1988, this reagent combination (109) is a source for MeS+, so its use does not lead to any formation of disulfides [87]. First, 109 is attacked by indole and a demethylation of sulfur occurs leading to 3-(methylthio

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

• berberrubine and berberine derivatives were synthesized by the Cu2+-catalyzed Chan–Evans–Lam coupling of berberrubine with arylboronic acids and subsequent 9-O-methylation. The reaction is likely introduced by the Cu2+-induced demethylation of berberrubine and subsequent arylation of the resulting 10-oxyanion

• products 4b–f was available in low yields (16–26%) by the Chan–Evans–Lam coupling of berberrubine (1b, Scheme 1). The formation of the 10-O-arylated products may be explained by an initial Lewis acid-catalyzed demethylation of berberrubine (1b) [38] to derivative 6 (Scheme 2) that reacts subsequently in

• ; with 5% v/v DMSO) in the absence and presence of 5a (A), and 5d (B) at LDR = 0 (black), 0.05 (orange), 0.2 (blue), 0.5 (green), 1.0 (red). The arrows indicate the changes of CD and LD bands with increasing LDR. Synthesis of 10-O-arylated berberine derivatives 5a–e. Cu2+-catalyzed demethylation of

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

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• DddL [20], DddP [21], DddQ [22], DddY [23], DddW [24], and DddK [25] have been described (Scheme 2A). Furthermore, a demethylation pathway is known through which DMSP is first converted into methylmercaptopropanoic acid (17) by the tetrahydrofolate (FH4)-dependent demethylase, DmdA (Scheme 2B) [26

• labelling into dimethyl disulfide (DMDS), the oxidative dimerization product from MeSH, showing the activity of the demethylation pathway in these bacteria. However, knockout of the dmdA gene in R. pomeroyi still gave a low incorporation of labelling into DMDS, suggesting the presence of another gene

• responsible for the demethylation activity [28]. Also the labelling from (34S)DMSP was efficiently incorporated into DMDS and dimethyl trisulfide (DMTS) [29]. Our previous investigations have also demonstrated that synthetic, i.e., non-natural DMSP analogues such as 3-(ethylmethyl)sulfoniopropanoate (EMSP), 3

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• observed. Instead, the partial demethylation of the amine occurred. As a result, a mixture of the products 6c and 6d (molar ratio 6c/6d = 1:4) was obtained. With the increase in the amount of palladium (15 mol %) the phthalazin-1(2H)-one derivative 6d was obtained as the main product (70%). Complexation

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• the N-Cbz-1-aminophosphonic monomethyl esters 12b,d and hydroxy esters 106 followed by the selective demethylation with TMSBr in a one-pot reaction. The method provides a mild route to prepare phosphonodepsipeptides. The yields were insensitive to the steric encumbrance of both reactants being coupled

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• demethylation pathway by action of the enzymes DmdABCD to methanethiol (MeSH, Scheme 1A) [12] or through lysis by DddD [13] or hydrolytic cleavage by one of the known DMSP lyases (DddW [14], DddP [15], DddQ [16], DddL [17], DddY [18] or DddK [19]) to dimethyl sulfide (DMS, Scheme 1B). It has already been

• of labeling into the sulfur volatiles 39, 40, and 42, which also questioned their natural origin. This finding is rather surprising for 42, especially regarding the feeding experiment with (34S)DMSP, because its formation would be explainable by a DMSP degradation through the demethylation pathway

• mass spectra of A) unlabeled 2-(methyldisulfanyl)benzothiazole (41) and of labeled 41 after feeding of B) (methyl-2H3)methionine, C) (methyl-13C)methionine and D) (34S)DMSP. Sulfur metabolism in bacteria from the roseobacter group. A) DMSP demethylation by DmdABCD, B) DMSP hydrolysis by DddP and lysis

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• -tetramethyl-1,3,2-dioxaborolane [23]. The electrophilic compound suitable for the projected cross coupling was obtained by mono-demethylation of commercially available 1-bromo-3,5-dimethoxybenzene (7) with boron tribromide (Scheme 3). A satisfactory yield of phenol 8 was observed with 0.9 equivalents of the