Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• -type siderophores. Structurally, compounds 1–5 are closely related to formobactin [10], brasilibactin [23], nocardimicin [24], and terpenibactins [15]. While the core scaffold of these natural products is conserved, they differ in the length of their fatty acid residues, their methylation pattern, and

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• oxidized to compound 4 with m-chloroperbenzoic acid under mild conditions, and compound 4 can basically maintain the original excellent stereoselectivity (Scheme 5a). Meanwhile, we are pleased that methylation of 3ah took place easily to afford product 5 in 95% chemical yield with 99% ee and >20:1 dr under

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• N-methylation [15]. The microwave-mediated reaction of 4-chloro-6-halo-2-phenylquinazolines 8a or 8b with o-toluidine (14a) in THF/H2O could be accomplished within 2 h and afforded the corresponding quinazoline derivatives 15a and 15b in 74% and 78% isolated yields, respectively. In addition, when

• and 8b. Conditions: a) NBS, CH3CN, 30 min, 25 °C; b) H2O, H2O2, I2, 24 h, 50 °C. N-Arylation reactions using ortho-, meta-, and para-substituted primary anilines of type 14 followed by methylation of ortho-derivatives 15a–d, to obtain the desired 4-anilinoquinazolines of type 10. N-Arylation reactions

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• subsequent ring-contracting α-ketol rearrangement would form 89. From here, a series of oxidation, cyclization, methylation, and/or reduction steps yield 92 and 93 (each representing two isolated products, one with R = Me and the other with R = Et). Oxidation at C1 and α-ketol rearrangement to 91, on the

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• cofactor for methyl group transfer resulting in cytosine methylation. This recently discovered riboswitch-ribozyme activity opens new avenues for the development of RNA labeling tools based on tailored O6-alkylated preQ1 derivatives. Here, we report a robust synthesis for this class of pyrrolo[2,3-d

• scaffold. Keywords: deazapurines; heterocycles; pyrrolopyrimidines; queuosine; RNA cofactors; RNA methylation; Introduction Methylated preQ1 has attracted much attention recently because this compound has been found to function as cofactor for the conserved fold of a non-coding RNA, namely the preQ1

• class-I riboswitch [1]. This riboswitch acts as a ribozyme by using 7-aminomethyl-O6-methyl-7-deazaguanine (m6preQ1) as methyl group donor; it catalyzes self-methylation of a specific cytidine in the aptamer binding pocket, yielding N3-methyl cytidine (m3C) under release of 7-aminomethyl-7-deazaguanine

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• methylation of C–H bonds because it would provide a convenient access to structures that might not otherwise be available for biological testing [89][90][91]. Hence, Doyle and co-workers realized an elegant approach for the methylation of (hetero)aryl chlorides 8 using trimethyl orthoformate as a methyl

• cycle involving the generation of methyl radicals via β-scission of a tertiary radical which in turn was generated from trimethyl orthoformate by a photogenerated chlorine radical-mediated HAT process (Figure 14) [92]. Recently, Stahl devised a photoredox nickel-catalyzed methylation of benzylic and α

• . Proposed catalytic cycle for the nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides using trimethyl orthoformate. Proposed mechanism for the photoredox nickel-catalyzed hydroalkylation of internal alkynes. Proposed mechanism for the photoredox nickel-catalyzed acylation of α-amino C(sp3)–H

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• compounds with the same degree but different pattern of substitution, underscoring the importance of pure and well-defined polysaccharides for proper structure–property characterization. For example, compounds with an alternated methylation pattern resulted in quasi-linear structures, whereas more bent

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• , and the introduction of methyl groups has an attractive effect on the properties of medicinal compounds [135]. However, the selective late-stage methylation has a limited scope due to the lack of suitable methodologies [136]. The insertion of methyl groups at positions adjacent to heteroatoms often

• has a further effect improvement, however, it is even more challenging. In front of this, White and co-workers (2020) adopted a strategy consisting of an initial hydroxylation of the C(sp3)–H bonds adjacent to N- or O-heteroatoms followed by a methylation step (Scheme 19B and C) [137]. The

• ′-bipyrrolidine) controls the site- and chemoselectivity in the hydroxylating step of the methylene C(sp3)–H bond while milder oxidation conditions help to increase the chemoselectivity. The methylation step is accomplished using a modestly nucleophilic organoaluminium reagent (AlMe3) to activate the hemiaminal

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• the GT concentration at sub-lethal levels via redox cycling and S-methylation of active disulfides in GT, respectively [117][118]. Furthermore, in terms of exogenous factors, not only GT itself but several other biotic and abiotic factors, including neutrophilic granulocytes, media composition, pH

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• electron-rich benzylic position, rationalizing the involvement of electrophilic metallonitrene intermediate 18A. Manganese-catalyzed late-stage C–H methylation The incorporation of methyl groups has the potential to manipulate absorption, distribution, metabolism, and excretion (ADME), solubility, and

• protein–ligand binding properties as well as biological activities of small molecules, potentially leading to dramatic increases in potency, and thus has been widely explored in drug discovery [54][55][56]. Late-stage C–H methylation has recently been investigated using iron and cobalt catalysts as

• sustainable 3d metal catalysts [57][58], while manganese-catalyzed C–H methylations are scarce [59][60]. This disparity is due to the challenges in functional group tolerance of Mn-mediated late-stage transformations. The White group reported a late-stage Mn-catalyzed C–H methylation protocol that utilizes an

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• acetylation, methylation, and phosphorylation, which alter TF access; and iii) methylation of CpG islands in promoter regions that inhibit gene expression [4][5]. There are currently several isolated studies of TF–glycogene interactions, but a systematic “systems-level analysis” is absent. Many of these

• selecting 1 million TF–gene pairs. Linear regression and statistical analysis are then performed on the top 5% hits (positive and negative coefficients) to establish TF–gene correlations. This analysis accounts for target gene copy number, tumor purity, and promoter methylation extent; and iii) TF–gene

• glycosylation flux in cancer. Some TFs were found to interact with methyl CpG-binding TFs when regulating glycosaminoglycan proteins, implicating methylation as a possible modulator of glycosylation in cancer. Our TF–glycogene relationships, mined from Cistrome Cancer DB, represent a starting point for

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• N-methylation led to (−)-angustureine (107) in high overall yield (Scheme 31). The same methodology was applied to the synthesis of (−)-cuspareine (108), starting in this case from enantiomeric imine (RS)-104b, and using 2-(3,4-dimethoxyphenyl)ethylmagnesium bromide as Grignard reagent. A

• , which after desulfination and N-methylation led to expected (+)-sedamine (125) in 30% overall yield from ketone derivative 124. The stereoselective synthesis of trans-5-hydroxy-6-substituted-2-piperidinones was also reported by the group of Wei, taking advantage of the addition of Grignard reagents to N

• -sulfinyl imine 160. A subsequent base promoted cyclization of chloroamides (158 and 162) and the products 165 and 163 were obtained in 91% and 93% yields respectively. The N-methylation of alkaloids 163 and 165 using 37% formaldehyde and sodium borohydride formed the tetrahydroisoquinoline 164 and 166 in

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

• conditions to give the corresponding 9-methoxy-substituted derivatives 5a–e in moderate to good yields of 40–77% (Scheme 1). During the methylation of derivative 5f a transesterification occurred and a 2:1 mixture of the ethyl and methyl ester was formed that could not be further separated. The novel

• methylation. The straightforward synthetic route enables the synthesis of a new class of berberine derivatives from easily accessible starting materials. The derivatives bind with slightly higher affinity to G4-DNA as compared to the parent berberine (1a) and induce a moderate stabilization of telomeric

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• backbone modification occurs in ribosomal RNA (rRNA) of both pro- and eukaryotes [6]. A very common natural modification that concerns the ribose moiety is 2'-O-methylation (2'-OMe). 2'-OMe nucleotides are scattered throughout all types of RNA, including mRNA, tRNA, rRNA, snRNA, snoRNA, miRNA and viral RNA

• ) (TIPDS) protected uridine, protection of N3 was needed in order to prevent methylation at this position (Scheme 4). The N3-benzoylated derivative could then be treated with methyl iodide in the presence of silver oxide in order to methylate the 2'-OH. A similar strategy was employed to synthesize 3',5'-O

• -TIPDS-N4-benzoyl-2'-O-methylcytidine. Next, 3',5'-O-TIPDS-N6-benzoyladenosine suffered from methylation at the nucleobase and thus, 6-chloro-9-β-ᴅ-ribofuranosylpurine was instead used as the starting material. Once TIPDS protected, the 2'-OH could, once again, be selectively methylated with methyl

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

• -(allyldisulfanyl)propanoate (26) were observed. While the presence of 24 can be explained by the O-methylation of the DmdA product 37 with S-adenosylmethionine (SAM, Scheme 4E), compounds 25 and 26 require a second deallylation of 37 to 3-mercaptopropanoic acid (38) possibly by DmdA, the reaction with a

• corresponding thiol MeSH or 13, and O-methylation (Scheme 4F). Very similar patterns of volatiles were obtained in the feeding experiments of DAllSP with D. shibae and O. indolifex (Figure 2B,C, Table 1 and Figures S2 and S3 in Supporting Information File 1). An additionally observed compound in one analysis of

• ). While compound 23 can arise from AllMSP by deallylation to 3-(methylsulfanyl)propanoic acid (36), potentially through DmdA, and O-methylation, the derivative 24 may be formed analogously through intermediate 37 (Scheme 4A and E). The higher production of 23 in comparison to 24 suggests that the

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• observed within 16 h at rt, and the heteroaromatic compounds 1a–e could be isolated in good yields. Subsequent N-methylation with methyl trifluoromethanesulfonate in CH2Cl2 also proceeded smoothly with the BT-SRF reagents each being obtained after 48 h at rt in high yields upon precipitation with Et2O. As

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• inthomycins [36]. These triene moieties are a sub-unit of the oxazolomycin class of antibiotics. To prepare the phenyl analogue of racemic inthomycin C (rac-3), at first, the phosphonate 28 was prepared using a Claisen condensation of ethyl propionate (25) followed by methylation of 26a, treatment with

• benzoate to give (−)-141 in good yield. Next, the benzoate-protected ynoate (−)-141 was converted into aldehyde (Z)-(+)-143a by employing a copper-catalyzed methylation of the alkyne moiety to the corresponding enoate (Z)-(+)-142 followed by an ester reduction–oxidation sequence using DIBAL-H and TPAP

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

• -catalyzed intermolecular carboxylatve TMM [3 + 2] cycloaddition [36] of enone 65 and TMM donor 62 to forge the highly-substituted spirocyclic cyclopentane 66a [38] (Scheme 4A). Methylation of the resultant cyclopentane 66a gave methyl ester 66b in 93% yield over two steps. A six-step synthesis from ester

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• phosphate [28][29]) and moderate or low yields, on the one hand, and the need to obtain N7Me-Gua [30][32][33][34][35] and N7Me-dGua [31][34][36][37][38] by chemical methylation, the failure of Ara-1P synthesis [34], and the need to utilize N7-methylguanine, on the other. In a recently published work by

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• shifts for both 1H and 13C nuclei. Methylation of Lys and Arg occurs as posttranslational modification (PTM) of proteins in nature, often used as a switch to regulate protein interactions and thus their function [112][113]. The Crowley lab has used this advantage to study the binding of sulfonatocalix[4

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

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

• also obtained from 3m. S-Methylation of 3m was achieved in 91% yield with methyl iodide in the presence of NaH/THF and the S-benzylation has been carried out by a similar procedure (Scheme 5). To derive the mechanism of the reaction, a few control experiments have been executed (Scheme 6). Initially

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• ,6R)-13b. Intermolecular N-methylation of reduction product 7. Synthesis of pyrrolidinyl phosphonic acids 11a–d. Synthesis of tetrahydropyranylphosphonates 13a–f via diastereoselective Henry/acetalyzation reaction. Synthesis of (3,4-dihydro-2H-pyran-5-yl)phosphonate 14. Optimization of the conditions

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• nucleophilic substitution and then methylated. NDI 4 could be isolated in a yield of 60% after purification by column chromatography. In the last synthetic step, the molecule was triply methylated with iodomethane in acetonitrile at room temperature for three days. After complete methylation, purification by