Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• values of the primary (IC50 (CCRF-CEM) = 580 pM) and tertiary (IC50 (CCRF-CEM) = 54 pM) amine derivatives (Figure 1B) [20][35], showing a strict increase in cytotoxicity with increasing degree of aniline methylation. The same trend was also observed for unit D derivatives modified with amino groups [19

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• inductive methylation [24]. To research further the bioactivity of the pheromone, herein, we report an effective synthesis of the aggregation pheromone of T. castaneum, which uses the cheap (R)- and (S)-2-methyloxirane as chiral sources, connects two chiral building blocks through Li2CuCl4-catalyzed

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• as riboswitches [6][7][8] or the queuosine biosynthetic enzyme machinery [9][10][11]. Recently, even the self-methylation activity of a preQ1 riboswitch has been discovered with a methylated preQ1 derivative acting as a ribozyme cofactor [12]. Moreover, these analogs have found utility in several

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• dry DMF. The five-membered ring of this esterified benzisothiazole 2 was then expanded to form a six-membered cycle via a ring-expansion reaction in anhydrous conditions. In this reaction, the benzisothiazole scaffold was converted into a benzothiazine backbone 3 followed by N-methylation to obtain

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• the catalyst (Scheme 41) [69]. Following identical reaction conditions two series of different atropoisomers were prepared with very high yields, enantioselectivities, and diastereoselectivities. The corresponding products proved to be stable for up to 12 h in o-xylene at 120 °C. Methylation of the

• reported. The configurational stability and rotational barrier were also investigated. The enantioselectivity gradually decreased at 70 °C for 12 h in isopropyl alcohol and the calculated value was 28.5 kcal/mol. Control experiments proved the importance of N–H bonds during the reaction and methylation of

• product (75%), but at a significantly slower rate than the catalyzed one. Methylation of the oxygen in azaborinephenol 232 led to no product being formed. On the other hand, methylation of nitrogen in azaborinephenol 232 still provided the product in decent yield and enantioselectivity (79%, 89% ee

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• synthesis of benzo[j]fluoranthene 23 in six steps (Scheme 3). In this sequence, 1,8-DHN (19) was first converted to 1-acetoxy-8-methoxynaphthalene (24) via a selective mono-methylation of 19 followed by acetylation by acetyl chloride in 88% yield over two steps. The more electron-rich ring of naphthalene 24

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• , CHCl3), lit. −25 (c not specified, CHCl3) [24]; HRESIMS (m/z): [M + Na]+ calcd for C29H50ONa, 437.3754; found, 437.3741. Methylation of 3,5-dibromo-4-hydroxybenzaldehyde 3,5-Dibromo-4-hydroxybenzaldehyde (279.0 mg, 1.0 mmol) was dissolved in CH2Cl2/MeOH 1:1 (1 mL) then a solution of TMSCHN2 in hexanes

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• importantly, the application of 8 equiv of tert-BuLi induced the formation of N-methylation products (Scheme 6). Compounds 15a (15a’) and 16a (16a’) existed as two rotamers, in ratios of 1:1.15 and 1:1.76, respectively, with the predominant cisoid isomer. Transoid (trans 15a(16a)) isomers contained a larger

• -unsaturated amides. Formation of β-fluorinated and nonfluorinated α,β-unsaturated amides. Michael addition of 1a–d with tert-BuLi. Michael addition of 2a–d with tert-BuLi. Formation of N-methylation products. Optimization of reaction conditions. Supporting Information Supporting Information File 40: Detailed

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• ). Dehydrogenation of the latter with DDQ afforded the anomerically pure indol-N-glycoside β-26a which upon benzylation and methylation gave products β-27a and β-27b, respectively. Iodination gave products β-28a and β-28b, however, due to the basic reaction conditions (I2, NaOH, DMF), ether rather than ester

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• ) starting from the oxoester 3, which is conveniently available from propenylpiperidine (2) [27] and methyl acrylate [28]. The Wittig reagent 1-methylheptyltriphenylphosphonium iodide (5) was prepared by methylation of the Wittig salt of heptyl iodide (4). A Wittig reaction with 3 afforded an E/Z mixture of

• heated to 60 °C for 60 min and then excess MSTFA was removed with a stream of N2. The sample was taken up in CH2Cl2 and analyzed by GC–MS [42]. Methylation with TMSH: An extract (100 µL) in a 2 mL GC vial was mixed with 50 µL trimethylsulfonium hydroxide in methanol (TMSH, 0.25 M) and allowed to stand at

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• bioactive compounds such as caffeine and prothioconazole (Scheme 2a). Additionally, Lin, Terrett and Neurock's group [8] reported the electrochemical C(sp3)–H methylation of complex molecules. This strategy enabled the synthesis of the "magic methyl" product, a TRPA1 antagonist (Scheme 2b). C–H bond

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• synthesis, the deprotected derivatives such as 69 are desired for the synthesis of natural products. Therefore, an easy-to-perform two-step deprotection procedure was developed that is based on methylation of the phenolic hydroxy group with an excess of MeI in acetone at rt (68), followed by oxidative

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• mammalian glycans rely on a group of “only” 10 monosaccharide units, they can be assembled, in linear or branched chains, through different glycosidic linkages and diverse spatial orientations, which can also undergo modifications, such as methylation, sulfation, and phosphorylation, resulting in a plethora

• able to add branching points and some sugar derivatisation, including methylation and acetylation. The user has also the possibility to choose the ring type and the anomeric configuration of each monosaccharide. Once the structure is complete, it is possible to download not only the generated .pdb

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

• (hetero)aryl-3-(methylthio)-2-propenones 94, are accessible through Claisen-type thioacylation of methylketones, followed by methylation. These intermediates serve as precursors for the concomitant cyclization with arylhydrazines in a consecutive multicomponent reaction to regioselectively give pyrazoles

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• , 332.1832; found, 332.1838. Methylation of 1 Allostreptopyrrole A (1, 2.0 mg, 0.007 mmol) and K2CO3 (4.4 mg, 0.032 mmol) were stirred in dry DMF (0.5 mL) at 50 °C for 10 min. Methyl iodide (19 μL, 0.32 mmol) was added and the mixture was stirred at this temperature for 12 h [29]. Reaction completion was

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• , introduce hydroxy groups at C8 and C16 to produce FD-8β,16-diol (7), and BscE-catalyzed O-methylation generates the putative intermediate 8. The subsequent oxidative allylic rearrangement (8→9), catalyzed by the nonheme iron(II) and 2-oxoglutarate (Fe(II)/2OG)-dependent dioxygenase BscD, was a key step

• pentacyclic core scaffold of 5. Overall, the single NRPS module SfmC is responsible for the construction of the highly functionalized scaffold 93 from the two simple amino acid derivatives 86 and 88. After NRPS-catalyzed scaffold assembly, SfmM1-mediated N-methylation at N12, and subsequent SfmO2/O4-promoted

• chemo-enzymatic total synthesis of jorunnamycin A (103). SfmC-catalyzed enzymatic conversion followed by cyanation and N-methylation also converted substrate analog 101 to the corresponding pentacyclic tertiary amine 102 in 18% overall yield based on peptidyl aldehyde 101. Subsequent simple chemical

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• allowing methylation at various positions. The different possible acceptor regions in ribosomally synthesised peptides are described in this article. Furthermore, we will discuss the potential application of these methyltransferases as powerful biocatalytic tools in the synthesis of modified peptides and

• other bioactive compounds. By providing an overview of the various methylation options available, this review is intended to emphasise the biocatalytic potential of RiPP methyltransferases and their impact on the field of natural product chemistry. Keywords: biocatalysis; methylation; post

• contrast to ribosomal peptide biosynthesis, many non-proteinogenic amino acids can be incorporated as building blocks. However, RiPP pathways are more flexible and they represent interesting biotechnological production routes. In this review, we will focus on post-translational methylation reactions. A

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• interactions in the marine environment may be broadly shared [132]. Further examples of shared natural products are delineated below. Aliphatic and aromatic hydrocarbons (2Z,4E)-3-Methyl-2,4-decadienoic acid (25, Figure 9), an unsaturated fatty acid with unusual methylation pattern was isolated and identified

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• could be easily carried out by catalytic hydrogenation to produce 6 (Scheme 6a). On the other hand, 4ax could smoothly undergo N-methylation with MeI to give product 7 in quantitative yield (Scheme 6b). Conclusion In conclusion, we have developed an efficient method to rapidly synthesize 2-benzyl-N

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• the several alcohols and primary amines in the presence of t-BuOK (0.75 equiv) in toluene at 80 °C for 24–48 h and selectively produced the N-alkylated products with good yields (Scheme 3). More interestingly, the first non-noble-metal catalyzed the most challenging N-methylation of amines with

• generation of manganese PNP pincer complexes for the N-methylation of aromatic amines with methanol [35]. Various primary anilines were methylated selectively with good yields using Mn2 (2 mol %) and t-BuOK (0.5 equiv) as a base at 100 °C for 16 h (Scheme 4). Compared to their previous report, the N

• -methylation of amines with methanol was achieved with lower catalyst and base loading. Sortais et al. reported an elegant example of a manganese-catalyzed N-methylation of primary amines with methanol using catalytic amounts of base. They synthesized a novel Mn(I) complex bearing a bis(diaminopyridine

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• methyltransferase (IPPMT) from Streptomyces monomycini. Notably, polymethylated C41, C42, and C43 carotenoids were produced by combining the endogenous terpene biosynthesis pathway and IPPMT, demonstrating the potential of this approach to expand the terpene structural space [52]. In addition to methylation of the

• coelicolor [55] (Figure 8a). Further structure-based engineering of BezA successfully repurposed it to catalyze the unprecedented C6-methylation of FPP by a single residue substitution in its substrate-binding pocket [55]. Moreover, efforts have also been made to engineer the TSs to modulate their product

• selectivity with the noncanonical prenyl substrates. To enable the biotechnological synthesis of irregular terpenes, the product selectivity of 2-methylenebornane synthase from Pseudomonas fluorescenes was altered using a semi-rational engineering approach [56]. In contrast to GPP methylation, modification of

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• methylation of the intermediate diacid. As for the 1,2-cubanes, the authors were able to derivatise this general building block into a range of other 1,3-cubanes via metallophotoredox catalysis using acid 167 and redox active esters 168 and 169 (Scheme 17B) [51]. Arylation (to 170), amination (to 171) and

Introduction of a human- and keyboard-friendly N-glycan nomenclature

• Friedrich Altmann,
• Johannes Helm,
• Martin Pabst and
• Johannes Stadlmann

Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53

• -vertebrates contain numerous “unusual” and remarkable structural features such as methylation, sulfation, and zwitterionic non-sugar substituents, again glucuronic acid and often unusual architectures such as substituted core-fucose just as an example [44][52]. While the methylated moss glycans are accessible

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• II, which could be transferred to III by cyclization and epoxidation. Oxidation and methylation of intermediate III would produce IV. Compounds 1–4 could be obtained by nucleophilic attack at C-8 with the hydroxy or thiol group from IV via intermediate V, followed by oxidation and cyclization