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

• natural antibiotic nucleocidin [203][205]. Damha reasoned that the incorporation of fluorine at both C2' and C4' could lead to a stable nucleoside due to the glycosidic bond stabilization brought about by 2'-fluorination [206] which turned out to be correct after successful isolation of both 2',4'-diF-rU

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• -withdrawing groups than one chloro substituent’ [7]. Fearing instability of a hypothetical bis(aryloxy)chloromethane intermediate, we initially anticipated that the number of literature reports detailing the isolation of bis(aryloxy)fluoromethanes as byproducts [2][3][4][5], albeit in very small amounts

• undesired isomer were produced, recovery of unreacted 6 was simple and the quantity of 8 (<5%) was reduced compared to all previous attempts. Chromatographic separation permitted the removal of 8 and the isolation of a pure sample of compound 4. Synthesis of compound 1 Having produced the key intermediate 4

• in Scheeren’s method must be constructed with electron-rich arenes under highly acidic conditions. Furthermore, the method detailed in this work is operationally simple, not requiring the use or isolation of unstable intermediates and giving electron-poor bis(aryloxy)fluoromethanes in a single step

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• thionation reactions, considerable efforts have been devoted to the improvement of the workup procedures of these reactions. For example, Soós and co-workers introduced perfluoroalkylated derivatives of LR, which simplified the product isolation via a fluorous reversed-phase solid extraction technique [9][10

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• = 20; C = 57%) and allowing for the isolation of (Rp)-2 in 39% yield (94% ee) and (Sp)-3a in 53% yield (71% ee) (Table 1, entry 11). Mechanistically, this resolution process should proceed via the well-understood formation of a chiral acyl-transfer species between the isothiourea catalyst ITU 2 and the

• that allow for the kinetic resolution of racemic 4-hydroxy[2.2]paracyclophane (2) by means of an acylation with isobutyric anhydride (4a) in the presence of the chiral isothiourea catalyst HyperBTM (ITU 2). The reaction can be carried out with an s-factor around 20 and allows for the isolation of

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

• cyclization reactions based on the persistent radical effect. Heating them to 150 °C in tert-butanol provided diverse 1,3,4-trisubstituted pyrrolidones (Table 3). For stability reasons the initially obtained silyl-protected lactams 10a–k were deprotected without isolation by TBAF in THF affording hydroxy

• bond cleavage by mCPBA furnishing bicyclo[3.3.0]octandiones 18. The isolation of a mixture of four diastereomers as in the starting material indicates that radical coupling by TEMPO proceeds with exclusive diastereoselectivity (vide infra). Discussion The sequence nucleophilic epoxide opening/Brook

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds

• reaction was carried out in an acetonitrile/water (4:1) mixture similar to the procedure reported by Y. Xia et al. [23] that allowed the isolation of the target compound in 50% yield. The temperature was proved to play a key role in the cyclization, however, above 150 °C conversion decreased due to

• led to a better yield at 140 °C than in the acetonitrile/water mixture. Finally, we tested NMP as a green solvent that is also one of the safest choices for performing high-temperature MW-assisted syntheses (high boiling point, nonvolatile). Even though it brings difficulties towards product isolation

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• cholesterol 44 and histamine 45. Scientific literature [97] reports a three-step continuous synthesis of [6,6]-tert-butyl phenyl-C61-butyrate 47 based on tert-butyl 4-benzoylbutyrate hydrazone in a microstructured flow reactor that eliminates the need for stage-by-stage isolation of intermediate products and

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• synthetic methods for secosteroids is wide. However, usually these are multistep sequences exploiting toxic oxidants. Marine invertebrates are a rich source of oxidated and highly functionalized steroidal metabolites, including secosteroids. Since the first isolation of 9,11-secosterol from

• . Isolation of 9-hydroxysteroids A frozen culture supernatant was melted at room temperature or in a warm water bath, then poured into the separation funnel, saturated by the addition of solid sodium chloride and extracted with EtOAc. The extract was concentrated in vacuo to give a solid residue that was

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• thioamide nitrogen completely prevents the formation of the thiazole (route a). The rather complicated product isolation procedure of the Eschenmoser coupling reaction (route b) and the long reaction time taken together with problems connected with changing substituents throughout the molecule, encouraged

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• provide future chemists with hands-on experience in modern synthesis technologies. Apart from increased safety and scalability, reaction telescoping is one of the most attractive features of flow synthesis allowing for streamlined routes to minimize the need for the isolation and handling of potentially

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

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

• , was also reported in 1980 [10]. Following a 23-year hiatus, two papers submitted within two weeks of each other reported, respectively: (1) the isolation from Streptomyces sp. UMA-044 and characterization of NP25302, that differs from bohemamine in lacking the 6,7-epoxide functionality [11] and (2

• pxaAB gene cluster in E. coli, and analysis of the metabolites by differential 2D NMR spectroscopy, led to the isolation and characterization of pyrrolizixenamide A (9) and, subsequently, pyrrolizixenamides B–D (10–12). Ultimately, an analogous biosynthetic pathway to that proposed for the legonmycins

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• are noteworthy. It was found that all tested hydroxypyrrolines 1a–e and hydrazides 2a–g afforded the corresponding tetrahydropyridazines 3 (according to 1H NMR analysis of the crude reaction mixtures). However, due to the difficulties associated with their isolation and purification only few examples

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• situ from the corresponding active methylene compounds (Figure 1) [25]. In our syntheses we also used gem-dithiolates immediately, without isolation, except for the case when sodium trithiocarbonate (5a) was used. The reaction of 4 with 5a proceeds in DMF solution to give the corresponding 1,3-dithiole

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• 4 equivalents of a base were used, a series of differently substituted α-thio esters were obtained with up to 90% yield. On the other hand, employing 2 equivalents of a base, α-thio ketones were achieved after 18 h under air. Furthermore, after a shorter reaction time, the isolation of keto–enol

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

• product, but purification and isolation of the product by column chromatography was not possible ‒ neither with conventional nor with reversed phase methods. It turned out that the high polarity of the triol complicated its separation from other polar side products. To circumvent this problem, we decided

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• reaction of the Cl atom at the C2 position of purine with an excess of NaN3, and after chromatographic isolation. We obtained the pure azido-substituted phosphonate monoesters 9a and 9b in 28 and 23% yield, respectively (Scheme 4). The products 9a and 9b were further submitted to CuAAC reactions, but the

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• three steps) by the same method with diethylmalonyl chloride. This method also allowed for isolation of the open diamide–diamine 1a (77%). In addition, the similar potential ligands 1b–e (65–95%, Scheme 1b) were likewise prepared from amines B–E. The phenyl-substituted cyclam tetraamide derivative 2b

• trans product. Thus, the proper choice of the gold catalyst allows highly stereoselective formation of either cis or trans cyclopropanation products and facilitates the isolation of pure isomers. Despite the chiral nature of these ligands, no enantioselectivity was observed in the test reactions

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• reported the reisolation of inthomycin A ((+)-1) and the first isolation of inthomycin B ((+)-2) from the strain of Streptomyces sp. Gö 2, and proved inthomycin A ((+)-1) to be identical with phthoxazolin A ((+)-1) [2]. Later, the reisolation of inthomycin B ((+)-2) and inthomycin C ((–)-3) was reported by

• . Many methods have been developed for the synthesis of inthomycins since their first isolation in 1990 [1]. Most of the reported methods have been directed towards inthomycin C (3) due to its thermodynamically more favored 4E,6E,8E-triene system. The regiochemical issues of installing the conjugated

• by oxidation of the resulting alcohol using the Ley-Griffith TPAP procedure [47][48]. Treatment of aldehyde 57 with the Ando phenoxy phosphonate 58a [49] gave the desired (Z,Z)-diene 59 as the major product (59/60 = 87:13). DIBAL-H reduction of 59 allowed the isolation of (Z,Z)-isomeric alcohol

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• [11]. As a part of the continuing studies to identify bioactive constituents from the Korean medicinal plants [13][16][17][18][19][20], previous phytochemical investigations on the MeOH extract of the twigs of C. sinensis have led to the isolation and characterization of triterpenoids [13], biphenyls

• , Sungkyunkwan University, Suwon, Republic of Korea. Extraction and isolation. Extraction and solvent partitions were performed in the same manner as described in [13]. The hexanes-soluble fraction (3 g) was separated over a silica gel column (hexanes/EtOAc 3:1) to yield seven fractions (H1–H7). Fraction H3 (0.4

• over a silica gel open column (CHCl3/MeOH 50:1 → 1:1) to furnish nine fractions (C1–C9). Fraction C4 (1.5 g) was fractionated into 12 subfractions (C4-1–C4-12) using an RP-C18 silica gel open column eluting with 70% aqueous MeOH. The subfraction C4-3 (30 mg) was purified by an isolation strategy using

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• %, 35%, and 50% combined in one spectrum) was applied, and the AGC target was increased to 500,000 while the maximum injection time was increased to 200 ms. For all MS/MS scans, a precursor isolation width of m/z 1.2 was used. The MS/MS scan resolution was 30,000 and the m/z range was 110–3,500. MS/MS

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• involving the isolation of 5-arylamino-1,2,3-triazoles 1i–k. Supporting Information Supporting Information File 414: Full experimental details and characterization data of all new compounds, crystal data and structure refinement for 3e, 3t, and 3ag. Supporting Information File 415: Copies of NMR spectra of

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

• bath preheated to 160 °C, and stirred for 2 h. Upon reaction completion, the aqueous work-up, isolation, and purification of the product was performed in the same way as described in the typical procedure 1. The titled compound was obtained as yellow solid (lit. [54] yellow crystals), yield 66% (96 mg

• completion, the aqueous work-up, isolation, and purification of the product were performed in the same way as described in the typical procedure 1. The titled compound was obtained as yellow solid (lit. [36] yellow solid), yield 76% (147 mg, 0.76 mmol). Alternatively, the same compound was obtained via the

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

• contained ithomiolide A (3), a pyrrolizidine alkaloid derived γ-lactone, I. s. derasa carried the sesquiterpene α-elemol (8) in the androconia. These differences might be important for the reproductive isolation of the two subspecies, in line with previously reported low gene exchange between the two

• studies on speciation (species formation), as species often consist of multiple subspecies diverging for a number of adaptive traits, such as color pattern or host plants, which can then cause reproductive isolation. As such, they offer an excellent system to study the mechanisms underlying

• color patterns (see Supporting Information File 1, Figure S1) [4], are widely distributed, and parapatric in north-eastern Peru [5]. Despite the geographic overlap in distribution, a recent genetic study showed limited gene flow [4]. Reproductive isolation in mimetic butterflies can be driven by

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• ., dichloromethane, 1,2-dichloroethane, and toluene, the former was chosen due to the high volatility of some products, which prevented the isolation from the latter higher boiling solvents. Finally, the G-I catalyst loading was tested for selected endiyne metatheses under Mori conditions. While oxaendiyne 2b