Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• temperature gave the NH-unprotected γ-lactam 5a and the drug (R)-rolipram 5b in 79% and 97% yields, respectively, with excellent enantioselectivity. Hydrolysis of γ-lactam 5a in 6 N HCl aqueous solution at 100 °C for 10 hours then led to the formation of (R)-baclofen hydrochloride (6) in 76% yield (Scheme 6

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• employed as acylation reagents [1][2][3]. The strong C–F bond makes acyl fluorides relatively stable towards hydrolysis and easier to handle than other acyl halides [4][5][6][7][8]. Their reactions with nucleophiles are typically less violent than for the corresponding acyl chlorides with acyl fluorides

(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

• -workers also reported the modification of these 1,2-BCHs to increase the number of derivatives accessible using this approach (Scheme 3B) [38]. Transformation of the naphthyl ketone moiety of BCH (±)-25d by Baeyer–Villiger oxidation followed by hydrolysis gave carboxylic acid (±)-26. Through Curtius

• alkenes including acrylates, vinyl sulfones, and acrylamides could all be incorporated and the number of accessible bifunctional 1,2-BCHs was increased further by chemical transformation (Scheme 3D) [35]. Among the reported transformations were reduction of the ketone (to (±)-34), hydrolysis of the

• homologation and hydrolysis led to aldehyde (±)-46 which could then be oxidised to acid (±)-47 using a Pinnick oxidation. BCH 42b also led to ester (±)-48 via a Horner–Wadsworth–Emmons reaction followed by hydrogenation of the formed alkene. 1,2-BCH 44 could be turned into amine (±)-49 by oxime formation and

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• carcinogenicity [3][4][5][6][7][8]. Biotic and abiotic degradation of cyclic nitramines often produce linear nitramine byproducts. For example, degradation of RDX and HMX by microbes or alkaline hydrolysis forms the linear nitramine 4-nitro-2,4-diazabutanal (NDAB) [9][10][11][12]. Linear nitramines are also

• orthologous protein sequences and could facilitate NNG hydrolysis in the active site (Figure S4, Supporting Information File 1). The function of these residues are being investigated. There are also several nearby conserved basic residues. The significance of these residues will be further discussed below

• , Supporting Information File 1). Notably, the YjgF protein previously proposed to aid in deamination of imines – a proposed direct product of NNG degradation by NnlA – is absent [20]. This observation suggests this protein is not needed to aid in glyoxylate formation. Therefore, imine hydrolysis to glyoxylate

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• chiral auxiliary 10a, and following a survey of conditions and isolation protocols, a 90% yield was obtained when 10a was heated in the presence of 2 equivalents of SOCl2 and 5 equivalents of pyridine in DCE. Flash chromatography of the chloroalkyl ether 11a resulted in significant loss due to hydrolysis

• groups were small, and attempts to prevent the formation of 13d by slow addition of alcohol 10d to a solution of SOCl2/pyridine in DCE reduced the yield of 11d to 14%. Heating sulfite 13d with tetrabutylammonium chloride led only to hydrolysis back to 10d without rearrangement, indicating that these

• sulfites were not intermediates in the reaction manifold. Furthermore, the isolation of some starting alcohols in the reactions of 10b and 10d following chromatography was attributed to hydrolysis of the corresponding dialkyl sulfite 13b and 13d on silica, a process that can be acid or base-catalysed [26

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• polyketides or peptides, and form an ester bond. Then, they catalyze either intramolecular macrocyclization to give macrolactones or macrolactams with attacking of internal nucleophiles (alcohols or amine), or hydrolysis to release linear acids or peptides (Scheme 1b). Although TE domains may display

• TycC TE, the precursor was effectively converted into the macrocyclic tyrocidine A (1), exhibiting a low rate of substrate hydrolysis (Scheme 2a). In addition, TycC TE demonstrated a broad range of substrate tolerance, as it can cyclize a series of decapeptide-NACs that contain non-native residues in

• , resulting in daptomycin (12) formation with a ratio of cyclization to hydrolysis of 3:1 (Scheme 4a). The significance of single amino acids for daptomycin bioactivity was evaluated, for instance, the substitution of ʟ-3-MeGlu12 by ʟ-Glu12 in Dap yielded a 7-fold increase of the MIC against B. subtilis

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• GGPP, followed by hydrolysis by acid phosphatase. GC–MS analysis revealed that AsCPS synthesizes the same product to ObCPS_11g (see Supporting Information File 1, Figure S4A and B). It should be noted that the stereochemistry of CPP needs further verification due to the lack of chiral resolution of our

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• first attempts in iPrOH did not provide the starting material conversion. The reaction in THF resulted in the full conversion of the starting material, but the analysis of the crude product revealed the quantitative formation of hydrolysis product 5a. Assuming the instability of intermediate 2a, a one

• -pot reaction was performed by adding sodium 4-methylphenylsulfinate in the first step which was followed by NaN3. As the result, the formation of hydrolysis product 5a and 2,4-diazidoquinazoline (6a) was observed. Next, the reaction 1a → 4a in DMSO yielded diazidoquinazoline 6a as a major product and

• hydrolysis product 5a. In MeCN the conversion to derivative 2a was stopped at 50% and was not facilitated by an extra addition of sulfinate. To our delight, in MeOH we observed the formation of intermediate 2a over 5 hours, and after the subsequent addition of sodium azide product 4a was isolated in 31

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• spectrometry (HRMS) analysis revealed the molecular formula of 1 to be C25H36O5, corresponding to the 4-desmethyl form of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester (Figure 2C). Furthermore, the molecular formula of 2 was determined to be C25H38O6, indicating that 2 is formed by the hydrolysis of the epoxide

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• -diisopropylphenylamine, could not be converted into the desired imidazolium salt (Scheme 1a, path b). Applying a range of conditions, including those successful on other annulated systems, led to unreacted starting material or hydrolysis products after work-up (see Supporting Information File 1) [5][18][19][23][24][25

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• cruciferous vegetables, as hydrolysis products from the metabolism of glucosinolates [1]. In 2017, Müller and her research team showcased the ability of BIMs to operate as anti-inflammatory drugs by acting as GPR84 agonists [2]. GPR84 is a protein-coupled receptor found in immune cells, which regulates a

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• 4aa [35] was isolated in 62% yield (Scheme 4). On the basis of the transformation of 3aa to 4aa, a tentative reaction mechanism is proposed. As shown in Scheme 5, the spiropyridazine-benzosultam 3aa was firstly oxidized to intermediate A. Next, an aziridine was formed with the hydrolysis of the amide

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• amounts of 2a were observed (Table 1, entry 1). The predominant side products were 2,2'-diiodobiphenyl and 9H-carbazole. The formation of free carbazole indicated the formation and subsequent hydrolysis of 2a. The presence of 2,2'-diiodobiphenyl suggests the reaction of 1a with iodide released by each

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• 1 (after drying the IL under vacuum for 16 h), there was a significant increase in product yield from 53% to 87%. Then, we investigated addition of water to BMIm-BF4, as the literature reports that the hydrolysis of the anion of this IL is quite slow in the presence of excess water (less than 5% BF4

• ‒ hydrolysis in a 1:1 in volume IL/water solution kept at 45 °C for 24 h) [105]. It should be noted that the same treatment carried out on 1-methyl-3-octylimidazolium tetrafluoroborate (OMIm-BF4) evidenced a much higher extent of BF4‒ hydrolysis. This is probably due to the weaker interaction between cation

• and anion of the IL as the length of the side alkyl chain increases, which makes the BF4‒/water interaction more effective. Although Saihara and co-workers demonstrated that BF4‒ hydrolysis generates HF, which reacts with the surrounding glass container yielding SiF62‒ (signal at −130 ppm in 19F NMR

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• including the degradation of lymphoid transcription factors [15][16][17] IKZF1, IKZF3, and SALL4 where the latter's degradation could result in a significant teratogenic effect [18]. In addition, these glutarimide derivatives are highly susceptible to hydrolysis and enzymatic cleavage under physiological

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• -dimethylacetamide (DMA) as the major component. Although this solvent has very similar properties as the mostly used N,N-dimethylformamide (DMF), it is highly stable and does not produce formate upon hydrolysis [49]. In the solvent system DMA/TEOA 3:1 (v/v), we could observe that carbon monoxide was formed, however

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• physiological conditions since the presence of this substituent significantly affects the pKa of the phenol: an apparent value of 5.68 ± 0.02 was obtained. This also impacts the basicity of the azomethine nitrogen and, as a consequence, increases the hydrazone’s susceptibility to hydrolysis. Nevertheless, both

• species (ROS) in vitro, which may be another mechanism through which the compound exerts its protective effects in the brain. From a drug development perspective, however, INHHQ has some pharmacological limitations, such as low solubility and certain susceptibility to hydrolysis in a water-rich medium

• (hdz-NO2). It is expected that those substituents impact the chemical (e.g., acidity and hydrolysis susceptibility) as well as the structural and spectroscopic properties of the compounds. Results and Discussion The methyl-substituted hdz-CH3 and its nitro-containing analogue hdz-NO2 were isolated as

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• by acid hydrolysis of 1 using the method developed by Tanaka et al. [16], in which the hydrolysates are derivatized with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. For compound 1, peaks were observed at retention times of 13.96, 20.83, and 22.16 min. The peaks at

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• classical organic solvents were used. The expected compounds are recovered by a simple filtration after hydrolysis and no purification is required. Those derivatives were studied for their antioxidant activities and the results are consistent with those reported in the literature indicating that phenolic

• hydrolysis (Table 2, entry 1). The same compound was synthesized by Molnar et al. in 53% yield after reaction in ChCl/urea at 90 °C [3]. When increasing the reaction temperature to 60 °C, product 3a was obtained with 94% yield after 1 h of reaction in Pro/Gly (1:2) (Table 2, entry 2). For comparison purposes

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• through the use of additional NaOH and refluxing the crude alkylation mixture. After heating for 3 h, the desired intermediates were recovered in acceptable yields over this two-step one-pot sequence. The amide hydrolysis of 7 and 8 to the desired free naphthylamines 9 and 10 proved challenging, but was

• nevertheless successful, albeit in low yields after an extended reaction time. We explored KOH and NH3 as alternatives to NaOH for this amide cleavage, and found the resulting yields less satisfactory. We also explored the amide hydrolysis under acidic conditions as well, though this resulted to almost

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

• oxidation with Br2 and hydrolysis, the bromoethyl phosphate 5.4. Finally, the quaternarization with trimethylamine produced 5.5 and the acetylation produced 5.6 PAF. The intermediate compounds like 6.2 (1-O-alkylglycerol) or the protected secondary alcohol 6.6, either as enantiopure or racemic forms, are

• deprotonation of solketal in DMF followed by the addition of oleyl alcohol tosylate. 9.3 was isolated after the hydrolysis in acidic conditions of the acetal protecting group. The protection of the primary alcohol required a protecting group that can be deprotected without affecting the C=C double bond of the

• hypotensive effects. First, Wissner et al. reported the synthesis of racemic sn-1-deoxy-PAF 11.8 (Figure 11) [91]. First, n-octadecanoic acid chloride (11.1) reacted with tris[(trimethylsilyl)oxy]ethylene (11.2) [92] to produce, after acidic hydrolysis and subsequent decarboxylation, compound 11.3. Then, the

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• extract a hydrogen from the ether C (sp3)–H bond to form radicals. Subsequently, a single electron transfer (SET) leads to the oxonium species. Then, the enamine generated in situ from methyl aryl ketone and pyrrolidine undergoes a nucleophilic reaction with the oxonium species followed by hydrolysis to

• ]. This pathway involves the presence of methanesulfonic acid and a large amount of metal oxide to obtain the target product with moderate to good yield. In 2015, a MnO2-catalyzed sequential oxidative alkylation of C(sp3)–H/C(sp2)–H CDC and hydrolysis of enamides with ethers was reported by Xu et al

• . (Scheme 34) [99]. The CDC reaction was initiated by a radical oxidative addition of C(sp2)–H and the final product was obtained by amide hydrolysis. The strategy provides a simple and practical method for synthesizing β-oxoketones. In 2015, Cai et al. reported a novel CDC of C(sp3)–H and C(sp2)–H bonds in

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• intercepts the nitroalkene 3 in a Michael-type addition forming intermediate B. Hydrolysis regenerates catalyst 1 that can then selectively condense with the α,β-unsaturated aldehyde 4 to form chiral iminium ion intermediate C. Iminium ion C reacts with intermediate B in a further Michael-type reaction. The

• developed in our previous work [17], we tried to introduce 6 as an acetaldehyde equivalent, adding water in the reaction system and Amberlyst-15 as a catalyst to accelerate the hydrolysis process (Scheme 2). To our delight, 6 as an acetaldehyde surrogate allows a slightly better yield with doubled

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• potency against cancer cells in the presence of a 3-OH group. Notably, hydrolysis of the C3-acetoxy group in pachymic acid to tumulosic acid increased the activity of the compound compared to the positive control (cisplatin), in some instances [36]. Concomitantly, the oxidation of the hydroxy group at C-3

• effects of compound 1 and related analogues could be realized by C-3 hydrolysis. In 2010, Liu et al. also demonstrated the major role played by changes at C-16 on antibacterial effects of F. pinicola steroids [33]. The acetylation at C-16 reduced the potency compared to the corresponding congener with a

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• [2,3-c][1,2,4]triazines was synthesized via a cascade sequence of hydrolysis and skeletal rearrangement of imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazin-7(8H)-ylidene)acetic acid esters in methanol upon treatment with excess KOH. Imidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazin-6(7H)-ylidene)acetic acid

• esters are also suitable substrates for the reaction. In this case hydrolysis and thiazole ring expansion were accompanied with the change of the thiazolotriazine junction type from thiazolo[3,2-b][1,2,4]triazine to thiazino[2,3-c][1,2,4]triazine. Keywords: N,S-heterocycles; ring expansion; skeletal

• ][1,3]thiazino[2,3-c][1,2,4]triazines 3a–i as a result of ester group hydrolysis and thiazolidine ring expansion to the corresponding thiazine (Scheme 3). The potassium salts 3a,b were isolated in 81 and 63% yield, respectively. Compounds 3c–i were used in further transformations without isolation. 1H