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

• electrophilic bromination of the corresponding phenol, followed by hydrolysis promoted by H2O2 [66]. Variations in the methods of 2-methylnaphthol (17) oxidation to menadione (10) with H2O2 were made by changing the catalytic systems in order to increase the yield and selectivity. These include the catalysis by

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

• form a salimethyloxazolinyl-thioester intermediate, which then undergoes a C–N bond opening resulting in an ester formation. Eventually, the thioester undergoes a hydrolysis reaction leading to compound 6. The compounds, which were discovered in this study, are members of the large family of nocobactin

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and

• ester group in turn to the aqueous solution. Addition of base would result in the hydrolysis of one ester group to the corresponding carboxylic acid. Product distributions indicated a two- to four-fold relative decrease in the hydrolysis rate constant of the second ester caused by the confined space in

• the cavitand, which enhanced the selectivity of the monoester product 45. Similarly, the monohydrolysis of α,ω-diisocyanate 46 was achieved using the water-soluble cavitand D (Figure 13b) [77]. The residual isocyanate group was buried deep in the cavity of D and protected from further hydrolysis. The

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• described by Ellman and co-workers, but the expected α-aminoboronate could not be isolated. Extensive hydrolysis of the starting ketimine occurred, allowing only the recovery of the 1-methyl-isatin precursor. In the light of this initial outcome, we started a detailed screening of reaction conditions (Table

• of water to the minimum necessary to solubilize the copper sulfate. Thus, performing the reaction in toluene/water 100:1, ketimine hydrolysis was almost entirely prevented and the yield of compound 2a raised to 52% (Table 1, entry 6). With regard to the ligand (Table 1, entries 7 and 8), PPh3 behaved

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• by a ROESY correlation between H-6'' and H-1'''. Subsequently, an acid hydrolysis of 1 afforded the products including daphnogitin, a ᴅ-glucose, and a ᴅ-xylose. The absolute configurations of glucopyranosyl and xylopyranosyl was further determined by HPLC analysis of the sugar derivatives (Supporting

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• further reacted with potassium cyanide to yield nitrile 12 [27]. Saponification of the nitrile was performed by exploiting the Pinner reaction with saturated HCl gas in methanol. This led to methyl indol-2-ylacetate (13) in 83% yield [28]. The hydrolysis of ester 13 was performed in the presence of

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• , in water as solvent, both electron-supplying and electron-withdrawing substituents decreased the rate of the hydrolysis of benzenesulfonyl chloride. They proposed, consistent with the claim by Hall [12], that with electron-supplying substituents the reaction proceeded, in part, by an ionization (SN1

• of hydrolysis measured in aqueous dioxane [22]. The observations concerning the specific rates were consistent with an SN2 pathway for the displacement of the chloride ion from the sulfur. However, for the trisubstituted 2,4,6-trimethylbenzenesulfonyl chloride, the SN2 mechanism does not give a

• simple rationale for the high specific rate of solvolysis observed and a partial changeover to an SN1 pathway was proposed. Vizgert [14][15] had previously suggested that the favored pathway for the hydrolysis of this substrate was by an SN1 ionization mechanism [25]. This proposal was based on the lack

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• H-7 and H-10 also showed weak correlation, which clearly supports the cis relation of the proton H-10. In this reaction, lactonization and hydrolysis of the Boc group to the corresponding amine were observed. The formation of lactone 8 as the major product can be explained by nucleophilic attack of

• the neighbouring carboxyl group, which was formed by hydrolysis of the corresponding methyl ester. For the synthesis of other isomeric β-amino acid derivatives, epoxide 7 was treated with two equivalent amounts of NaHSO4 [27] in methylene chloride/MeOH at room temperature (Scheme 3). The formation of

• . Synthesis of cyclic β-amino acid 6. Epoxidation of Boc-protected amino ester 4 and hydrolysis of epoxide 7 with HCl(g)–MeOH. Reaction of epoxide 7 with NaHSO4 in methylene chloride/MeOH. Synthesis of cyclic β-amino acid derivative 8. Suggested mechanism for the reaction of epoxide 7 with NaHSO4. Supporting

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• isomerization involves two routes: one through the hydrolysis of 22 leading to lawsone (4) and the subsequent addition of arylamines in position C2, and the other involves the addition of arylamines at position C2 of 22, leading to 24 with two equivalents of arylamine, which after hydrolysis of the imine at

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• data [72]. Moreover, the epimerization by the conditions of SMC is unlikely as it has been excluded by total hydrolysis of a late-stage SMC modified RGD peptide [67]. Analysis of the secondary structures of the cyclic peptides P2–P4 by CD spectroscopy also did not show a significantly increased α

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• . C–O cleavage, Figure 1A) through H-atom abstraction from a photoexcited intermediate, which produces an oxonium-type intermediate (in brackets). Hydrolysis of this intermediate then affords an alcohol product. Recently [16][17], we demonstrated that vinylogous analogues of this mechanism (Figure 1B

• -formyl product iii, a possible intermediate on the path to product i via imide hydrolysis. To better understand the mechanism of photocleavage and the appearance of the formyl product iii, we first identified the 2-nitroaryl-derived byproducts produced in this reaction. Model compound 1 was subjected to

• nitroso 3, and related compounds 4 and 5 are all consistent with the classical C–X cleavage mechanism and with hydrolysis of the presumed oxonium intermediate 6’, but are inconsistent with the production of formyl products. In contrast, photoirradiation of the same alkenyl ether 6 under acidic conditions

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• –Volhard–Zelinsky-type ring-opening reaction of 1a (Table 1). In this reaction, the corresponding acid bromide is formed in situ by heating with Br2 and a substoichiometric amount of PBr3; the acid bromide is then converted into 2,5-dibromopentanoic acid (2a) via hydrolysis during the workup under open-air

• . Lactone 1a (5 mmol) was allowed to react with Br2 (2.0 equiv) and PBr3 (5 mol %) at 80 °C for 24 h, with subsequent hydrolysis successfully affording in 2a in 90% yield (Table 1, entry 1). In the absence of a substoichiometric amount of PBr3, the transformation of 1a to 2a hardly proceeded (Table 1, entry

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• 74. Hydrolysis of the imine affords the final product 69. In 2020, Sun and Liu reported the iminyl cyclization could also be achieved with DMSO as a methyl-radical precursor [88]. In 2017, the Zhu group developed an Fe(acac)3-catalyzed cyanoalkylative dearomatization of N-phenylcinnamamides 75 for

• 166 which is oxidized by Fe(III) to a carbocation species 167. Subsequent attack by the nitrile affords the nitrilium ion 168 which upon hydrolysis gives the final product 164. Oxime esters and ethers represent a widely used starting material for the generation of nitrogen-containing heterocycles. Due

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• 13. The formation of the last-mentioned can be achieved by an initial PIFA attack on the homoallyl C=C bond [41][42][57][58] through the possible intermediates 14 and 15 alternatively (pathway b). Finally, alkaline hydrolysis of 13 upon work-up of the reaction mixture leads to the formation of target

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• methodology based on the trans-stereoselective epoxidation reaction of 2,3-dihydroisoxazoles followed by the regioselective hydrolysis of the corresponding isoxazolidinyl epoxide [15][16]. Very recently, we have reported the synthesis of γ-(hydroxyamino)-α,β-diols by the addition of Grignard reagents to

• -catalyzed hydrolysis of 10 with concentrated hydrochloric acid in acetone/water afforded diol 3 in excellent 93% yield. The crystallization of the crude product from a hexanes/CH2Cl2 mixture led to the preferential formation of the thermodynamically more stable 4,5-cis isomer (determined on the basis of a

• desired epoxide 5 in an acceptable 70% yield with excellent stereoselectivity as the sole syn isomer (dr > 95:5). It is worth noting that a small quantity of pyridine was added to prevent unwanted acid-catalyzed epoxide hydrolysis [31]. The stereochemistry of 5 was assigned later after pyrrolidine ring

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• derivative 17. This was obtained as a mixture of endo- and exo-sulfoxides. Esterification of 17 was carried out with dimethyl sulfate to give methyl ester 18, which was further reduced using dichloroborane and dimethyl sulfide to provide sulfide 19 in 80% yield in THF as solvent. Hydrolysis of compound 19

• nuclear Overhauser effect (NOE) NMR spectroscopy are useful tools to monitor and control the chirality when utilizing a modified 1,3-oxathiolane intermediate 65 obtained via enzyme-catalyzed selective hydrolysis. Hu et al. [61] established a green catalyst, STS, for the asymmetric synthesis of lamivudine

• -catalyzed hydrolysis of protected racemic nucleosides to synthesize the enantiomerically pure oxathiolane nucleoside analogues 1 and 2 (Scheme 41). The protected racemic nucleoside derivatives 95 were synthesized by tin-mediated N-glycosylation of the corresponding acetate precursor 94 with silylated

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• nitriles 1. At the last step of the reaction, a proton substitutes AlBr3, and final hydrolysis of the reaction mixture gives rise to nitriles 2. It should be noted that this AlBr3-promoted hydroarylation of acetylene nitriles 1 (Scheme 1) is a novel transition-metal (Pd, Pt, Rh, etc.)-free stereoselective

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• hydrolysis [8]. It has also been found that degradation of chitosan/dextran cryogels resulted in an average increase in pore size, possibly due to thinning of the pore walls and reduction in crosslinks [32]. In general, mechanical property analysis of degraded cryogels is a topic largely overlooked by

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• 5a, glyoxylic acid hydrate (4), and O-benzylvanilin-derived aminoacetal 3e (Scheme 4), when treated with 20% HCl or 70% HClO4 gave a colored complex mixture of decomposition products, probably due to the hydrolysis of the benzyl ether. Iwakuma et al. [15] reported the synthesis of 1,2,3,4

• difficult and resulted in a moderate yield of 12 (41%) due to insufficient differences in the Rf values of compound 12 and the by-product 2,3-dimethoxybenzyl alcohol (not shown), formed through the hydrolysis of 13 (Scheme 8). In this situation N-(2,3-dimethoxybenzyl)veratrylamine 10 was chosen as the

• proposed a plausible mechanism for the reaction of 6a with diluted HCl (Scheme 10). The mechanism consists of four major steps: the first step is an acid-catalyzed hydrolysis of the acetal function in 6a to afford aldehyde 15; the second step is the enolization of the aldehyde 15 to form the tautomeric

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• rapid epimerization during cinnamate hydrolysis. Later, in 2013 Pereda-Miranda and co-workers isolated ten compounds, namely brevipolides A–J (1–10), from the aerial part of Hyptis brevipes Poit. collected in Mexico [12]. The C6’S configuration was then determined by X-ray crystallographic data of the

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• shown in Figure S47 (Supporting Information File 1). Retention times (min) for the derivatized (ʟ-FDAA) threonine standards and for the observed peaks in the HPLC trace of each ʟ-FDAA-derivatized hydrolysis product under the reported conditions were as follows: retention times of standards: ʟ-Thr: 19.62

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• %), which arises from hydrolysis during work-up of the enamine that is formed from trapping of the lithiated epoxide by LTMP [9][10]. Omitting LTMP gave a significantly improved yield of the allylic alcohol 6 (79%, using BuLi and stannane 4 (3 equiv each)). This latter result suggests that

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• (Figure 2). The locations of the glucose unit and the methoxy group were confirmed from the observed HMBC correlations of H-1′′/C-9′ and 3-OCH3/C-3, respectively (Figure 2). Acid hydrolysis of 1 was conducted to analyze the aglycone and sugar moiety. The structure of the aglycone (1a) was confirmed as

• characteristic J value of the anomeric proton (1.5 Hz) confirmed the rhamnose as α-form (Figure 2) [10]. Acid hydrolysis of compound 2 afforded the aglycone, dihydrodehydrodiconiferyl alcohol (2a) [18], and ʟ-rhamnose ([α]D25 +9.0), which was identified in an identical manner to that of compound 1. The

• obtained by acid hydrolysis of 3 was confirmed based on 1H NMR and MS data [20]. The absolute configuration of 3a was established as 8S (a negative CE at 273 nm) based on the comparison of its ECD spectrum with the reported data [21]. Thus, the structure of compound 3 was determined as 8S

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• The concept of anion-binding catalysis was first penned by Schreiner et al. in 2006, who realized the acetalization of benzaldehyde (1) with a thiourea catalyst (3, Scheme 1) [30][31]. They proposed the reaction to proceed via thiourea-catalyzed orthoester hydrolysis, leading to the formation of a

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• the 1,2,3-triazole core strategically in the design of new compounds [18][19]. The explanation for this interest is associated with its resistance towards oxidation, reduction, and acidic or basic hydrolysis reactions that occur in phase I of human metabolism [20][21]. The application of this core