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Search for "acid" in Full Text gives 3047 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Pathway economy in cyclization of 1,n-enynes
Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173
- pathway-controlled approach using tryptamine ynamides bearing Michael acceptor moieties as substrates (Scheme 27) [38][39]. Under strong Brønsted acid catalysis, protonation of the carbonyl group was achieved, which facilitated a Michael addition between the electron-rich indole C3-position and the
- 133 (Scheme 27, path b). Through precise acid catalyst selection, the reaction pathways were strategically modulated to afford efficient construction of both 1H-pyrrolo[2,3-d]carbazole derivatives and spiro[indoline-3,3'-pyrrolidin]-2-one derivatives. In 2019, the Ye group reported a copper-catalyzed
- intramolecular cyclization of 1,7-enynes. Brønsted acid-catalyzed cycloisomerizations of tryptamine ynamides. Catalyst-controlled cyclization of indolyl homopropargyl amides. Angle strain-dominated 6-endo-trig cyclization of propargyl vinyl ethers. Angle strain-controlled cycloisomerization of alkyn-tethered
Research towards selective inhibition of the CLK3 kinase
Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172
- [22]. But because our goal is to enhance activity for CLK3, we cannot take advantage of this amino acid variation, and we had to investigate for other differences between CLKs. Here, we report our strategy and first efforts towards this end, starting from compound DB18 which is highly potent and
- , examination of the structure of CLK3 shows that this key lysine 241 is very close to the entry of the ATP binding site (Figure 1B). Lysine 241 could be considered as an opportunity to design new molecules with an improved affinity to CLK3, by adding specific interactions with this amino acid bearing a primary
- amine in terminal position. Based on this, our strategy was to design new inhibitors with introduction, in their terminal part, of an acid group which could perform an extra hydrogen bond or a salt bridge with lysine 241 and therefore could be specific to CLK3. Towards this goal we started from our
A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures
Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171
- derivatization. Several derivatization methods using chiral anisotropic reagents, including α-methoxy-α-trifluoromethylphenylacetic acid (MTPA), phenylglycine methyl ester (PGME), and Marfey’s reagents, are widely used [8][9][10], although their applicability is restricted by the presence of specific functional
- Discussion Our degradation strategy of natural products bearing an MPO moiety includes (1) acylation of hydroxy group, (2) oxidative cleavage of olefin to generate 3-acyloxy-2-methylbutanoic acid, and (3) its methyl esterification (Scheme 1A). We initially investigated derivatization strategies to enable LC
- . Alternatively, PNB ester (2S,3R)-9, the C3-epimer of 8, was synthesized from (2S,3S)-13 via a Mitsunobu reaction using p-nitrobenzoic acid (PNBOH) and DEAD in 39% yield for two steps [28]. The stereoisomers (2R,3R)-10, and (2R,3S)-11 were prepared in the same manner starting from commercially available (3R)-14
Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates
Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169
- were previously used for the synthesis of 7-nitroindole derivatives: heating in polyphosphoric acid (PPA) at 80 °C [24][25]. However, our attempt was not successful. Experiments with zinc chloride, the most commonly used Lewis acid catalyst in Fischer indole syntheses, also failed under various
- conditions. Finally, we were able to achieve the Fischer cyclization of compounds 7a–j by using p-toluenesulfonic acid monohydrate as catalyst in boiling toluene (method A, step 2) [26][27]. On the other hand, the one-pot synthesis of target compounds 3a–j starting from hydrazino derivatives 5a,b was
- 1) afforded hydrazones (E)-9a,b. According to LC–MS, only the (E) isomers were present in the reaction mixtures and in the crude products. Hydrazones (E)-9a,b were then cyclized by refluxing in toluene in the presence of p-toluenesulfonic acid monohydrate (method A, step 2). It is noteworthy that
A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines
Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168
- Shibazono, Narashino, Chiba 275-0023, Japan Research Center for Materials with Integrated Properties, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan 10.3762/bjoc.21.168 Abstract We report a method for determining the absolute configurations of chiral amino alcohols, amino acid esters, and
- amines. In this work, we report that the method was applied to chiral amino alcohols and amino acid esters. We also applied the method to chiral secondary amines, for which it is generally difficult to determine the absolute configuration due to the conformational complexity of their derivatives [33]. By
- comparing the observed and calculated sign of the CD Cotton effect, their absolute configurations were determined. Results and Discussion The probe 1 was prepared as described previously [41]. Probe 1–primary amine conjugates 2a–e were prepared by the reaction of 1 with chiral amino alcohols and amino acid
Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings
Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166
- following: a mixture 3-functionalized indole 19 (0.08 mmol), 2-alkynylaniline 20 (0.12 mmol), (R)-Rh1 (5 mol %), n-Bu4NOAc (0.08 mmol), 1-adamantane carboxylic acid (1-AdCO2H, 0.08 mmol) and MeOH/CHCl3 (1:1, 2 mL), under electrolysis (graphite felt (GF) anode and graphite (C) cathode, 2 mA, 5.6 F/mol) at rt
C2 to C6 biobased carbonyl platforms for fine chemistry
Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165
- level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims
- , and illustrating their high-value conversion methods towards fine chemicals. Review C2 biobased carbonyl platforms Glycolaldehyde Developing accesses from biomass to structures such as glycolic acid (GA) and glycolaldehyde (GCA) with high atomic economy is challenging. Hu et al. reported a new route
- –Crafts alkylation products were then converted into an intermediate tryptaldehyde that underwent intramolecular olefination to form the targeted product [34]. Glycolic acid (GA) The growing impact of fossil fuel consumption has heightened the need for advancing renewable energy technologies. One
The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products
Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164
- on the reported method for asymmetric transfer hydrogenation of commercially available cyclopentadione 62 [54], the authors adapted an efficient method for the desymmetric enantioselective reduction of 62 using commercially available (R,R)-Ts-DENEB (63) as the catalyst and formic acid as the hydrogen
- -catalyzed intermolecular Diels–Alder reaction of 106 with methacrolein 107 afforded the common intermediate 108 in high yield. Sequential Grignard reagent addition and acid-promoted ethoxy elimination provided the separable planar diene 109 (dr = 1:1), which underwent a Mn-catalyzed HAT hydrogenation to
- give (15R)-110 and (15S)-110 in 65% and 54% yield, respectively. Subsequently, ten functional group manipulations of the diastereomeric mixture 110 produced ketoester 111. Finally, the introduction of conjugated double bond in 111 followed by hydrolysis of the methyl ester to carboxylic acid and DCC
Multicomponent reactions IV
Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163
- between an aldehyde, an amine, a carboxylic acid, and an isonitrile in 1959 [8], which marked the beginning of modern MCR chemistry, continues to attract undiminished attention. It has since been applied in manifold ways, from breathtaking reaction sequences and post-Ugi transformations to the generation
Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B
Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162
- compound 14, an intermediate in our synthesis of (–)-isochaetominine A (4) [63]. Indeed, EDCI/HOBt-mediated lactamization of 14 derived amino acid (not shown) via debenzylation increased the yield of (–)-isochaetominine A (4) from 75% to 91% (Scheme 1). Thus, overall yield of the total synthesis of
- (–)-isochaetominine A (4) increased to 30.8% over five steps. Similarly, EDCI/HOBt-mediated lactamization of amino acid (not shown) derived from 15 [63] via debenzylation produced the known (–)-2,3,14-tris-epi-isochaetominine C (16) with a significantly increased 92% yield. The epoxidation-triggered stereodivergent
- , anthranilic acid, and ᴅ-tryptophan”. Such speculation regarding the absolute configurations is clearly not convincing. Moreover, neither optical rotation data nor melting point (both 12 and 13 were isolated as white powder) have been reported by Liu et al. [32]. Additionally, the solvents used for measuring
Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design
Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161
- introduce the carboxylic acid group a sequence of formylation/oxidation reactions was used. Vilsmeier–Haack reaction of 1 afforded 6-oxoindolo[1,2-c]quinazoline-12-carbaldehyde (2) (Scheme 1). All attempts to oxidize the aldehyde group of 2 to the corresponding carboxylic acid were hampered by the oxidative
- sensitivity of the indole moiety, resulting in poor selectivity and formation of complex product mixtures. In particular, Jones oxidation of 2 gave the corresponding 6-oxoindolo[1,2-c]quinazoline-12-carboxylic acid (3) in a low yield (Scheme 1) making it necessary to look another synthetic pathway. Of
- (5) (Scheme 1), a structural analogue of the biologically active alkaloid tryptanthrin (Figure 1). An alternative scheme to indolo[1,2-c]quinazoline-12-carboxylic acid (3) was based on initial acylation followed by a haloform reaction. Refluxing compound 1 with trifluoroacetic anhydride (TFAA) in
Bioinspired total syntheses of natural products: a personal adventure
Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160
- symbiotic natural products. The proposal lacks strong evidences, no matter it is scientifically reasonable or not. The bioinspired synthetic would provide evidences to support such a plausible biogenetic pathway through chemical transformations under simple biomimetic reaction conditions like acid, base, or
- aldehyde 3. This linear aldehyde would be activated by an acid to trigger a key Prins cyclization with the trisubstituted olefin through reaction model 3 and generate a putative tertiary carbocation to be trapped by the chiral alcohol, providing bicycle 4 stereoselectively. Finally, the last olefin would
- with an acid and base-promoted saponification inversed the C12 alcohol stereochemistry, which ultimately provided (12R)-hydroxymonocerin. Total synthesis and bioinspired skeletal diversification of (12-MeO)-tabertinggine In 2013, Kam and co-workers reported the discovery of two novel indole alkaloids
Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid
Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158
- -triazoles, pyruvic acid, and salicylaldehydes were studied under different conditions. Upon conventional heating, benzotriazolooxadiazocine-5-carboxylic acids were formed in the three-component reactions as single reaction products. Upon ultrasonic activation or mechanical stirring at room temperature, the
- also was described in several other publications [13][14][15]. On the other hand, three-component reactions of aminoazoles, salicylaldehyde, and esters (or amides) of acetoacetic acid with isolation of other types of heterocylic compounds were described in some papers [16][17]. Our early works were
- devoted to the study of the reactions of aminoazoles, pyruvic acid and its derivatives with salicylaldehydes and it was found that depending on the conditions (reaction time, temperature, and method of process activation, in particular ultrasound and microwave irradiation), different types of heterocycles
α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions
Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157
- library of bis- and tetraamides was synthesized by the Ugi reaction with α-ketoglutaric acid, tert-butyl isocyanide, aromatic aldehydes, and aromatic amines. When o-azidoanilines were used, azidated peptidomimetics were obtained, the post-cyclization of which by the aza-Wittig reaction yielded a series of
- substituted 3-(3-oxo-3,4-dihydroquinoxalin-2-yl)propanoic acids containing a pharmacophore quinoxalinone moiety. The tandem Ugi/aza-Wittig combination was also carried out in a one-pot procedure without isolation of the intermediate. Keywords: α-ketoglutaric acid; aza-Wittig reaction; multicomponent reaction
- nitrogen-containing heterocyclic compounds using various modifications of this sequence [32][33][34][35][36]. Among others, Yan et al. [31] described a facile way to quinoxalinone derivatives using an Ugi/Staudinger/aza-Wittig tandem combination with pyruvic acid or phenylglyoxylic acid. Quinoxalinones are
Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis
Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154
- chemoselectivity towards diene formation (Table 1, entries 15 and 16). In accordance with the proposed reaction mechanism (Scheme 2), an equimolar amount of protons is generated in the reaction, which would likely induce the formation of additional side-products either by protodecupration [27] or the acid
- acid, its sodium salt or the silylated carboxylic acid), the arylation reaction of aliphatic chain-containing propargylsilane 7b (standard conditions; see Scheme 3) only resulted in the arylation of the oxygen nucleophile itself. Next, we proceeded to expand the substrate scope by exploring other
- internal nucleophiles (Scheme 4), that could be used instead of the alcohol. The carboxylic acid-containing silane 7 (R = COOH), which was obtained by stepwise oxidation of the alcohol 7d, failed to give the desired lactone 8t product due to O-arylation of the carboxylic acid, leading to phenyl alkyl ester
Photochemical reduction of acylimidazolium salts
Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153
- suitably electrophilic substrate at the carboxylic acid oxidation level provides an acylazolium species B, which typically reacts directly with nucleophiles or may first be transformed into the corresponding enolate derivative. Regardless of the individual pathway, NHC-catalyzed reactions of this type
- acid derivative substrates [16]. Over the last few years, a wide range of valuable NHC-catalyzed transformations have also been developed that incorporate redox steps. As an enamine species, single-electron oxidation of a Breslow intermediate is comparatively favored with the resulting open shell
- manifold with carboxylic acid derivatives, numerous coupling processes affording ketone products have been developed. Since the initial report from Scheidt and co-workers using 4-alkyl-substituted Hantzsch esters as coupling partners [31][32][33][34][35][36], several alkyl radical sources have been
Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization
Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152
- reaction at 50 °C for 36 h, and extensive decomposition of the starting material β-keto ester 15 occurred (Table 1, entry 1). Solvent screening of EtOH [26], acetic acid [26], and hexafluoroisopropanol (HFIP) [27] demonstrated that HFIP afforded optimal results, delivering cyclopentanone 14 in 63% yield as
- was treated with p-toluenesulfonic acid (p-TSA) in EtOH at room temperature to afford ketal 24 in 83% yield as a single diastereomer. Subsequently, palladium-catalyzed decarboxylative allylation delivered compound 25 in 89% yield. The efficiency of our first-generation strategy for asymmetric
Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis
Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151
- . Lipases commonly share typical sequences of α-helices and β-strands and possess a catalytic triad consisting of serine (Ser), histidine (His), and aspartate (Asp) or glutamate (Glu). These three amino residues function as a nucleophile-base–acid catalytic system to facilitate esterification, and the
- Lewis acid-mediated semi-pinacol rearrangement, this work involved a CRL-catalyzed desymmetrization of prochiral diol 51 (prepared from aldehyde 50 in four steps), providing monoester 53 in 57% yield with 83% ee. Notably, 1-ethoxyvinyl 2-furoate (52) was selected as the acyl donor in this step to
- functional group manipulations, alcohol 103 was subjected to enzymatic oxidative kinetic resolution with the bacterium Gluconobacter oxydans, producing alcohol 104 and acid 105. The alcohol 104 with the desired C9 stereocenter was then converted into fragment 106 in nine steps, while acid 105 was recycled to
Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads
Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150
- ][3]. Established sets of reactive probes are typically armed with electrophilic warheads that have the potential to target nucleophilic amino acid side chains. Most reactive probe sets bear cysteine-directed warheads [3][4][5][6][7], although sets have also been designed to target a wider range of
Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs
Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148
- oxidation of amide and other amino acid side‐chain fragments. By tracking changes in this oxidation signal upon addition of an alkylating agent, we can infer whether the agent has effectively reacted with (and thus structurally altered) the protein. As illustrated by the black trace in the LSV plot, pure
- . When these agents alkylate the HSA amino acid residues (particularly reactive sites like lysine, cysteine, serine NH2, SH, OH-side chains, and possibly other nucleophilic groups), the resulting covalent modification can disrupt the electroactive centers responsible for the protein’s oxidation peaks
Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines
Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147
- for different N-benzyl benzaldimines in moderate to good yields. In 1991, Shono’s research group described the electroreductive intramolecular coupling of aromatic diimines, carried out in DMF in the presence of methanesulfonic acid in a divided cell equipped with a lead cathode, a carbon rod anode
- reaction and a screening of reaction parameters such as solvents, electrodes materials, electrolytes, total charges, and concentrations of the reaction mixture was performed. All optimization studies were carried out using 0.5 mmol of 1a in the presence of methanesulfonic acid in an undivided cell (5 mL
- co-workers [44], the presence of a strong protic acid, such as methanesulfonic acid, MsOH, is essential to promote the intramolecular coupling. A control experiment revealed that when the electroreduction of 1a was performed in the absence of MsOH (Table 1, entry 3), no formation of the desired
Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition
Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146
- the presence of a Lewis acid. The use of BF3·OEt2 gave a low yield of the desired alcohol 2 [29]. This was improved slightly with Sc(OTf)3 as the Lewis acid, which could be used substoichiometrically [30]. The alcohol 2 was converted to the tosylate 3 and subsequent ozonolysis gave the aldehyde 4. The
Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules
Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145
- with the more recently introduced inherent chirality. As one of the most prominent chiral organocatalysts, chiral phosphoric acid (CPA) catalysis has proven highly effective in synthesizing centrally and axially chiral molecules. However, its potential in the asymmetric construction of other types of
- within this domain. Keywords: asymmetric catalysis; chiral phosphoric acid; helical chirality; inherent chirality; planar chirality; Introduction Since the seminal works by Akiyama [1] and Terada [2] et al. in 2004 demonstrated the application of BINOL-derived chiral phosphoric acids (CPAs) in
- catalytic sites. The OH group on the phosphorus atom functions as a Brønsted acid site, while P=O serves as a Lewis base site, which enables the simultaneous activation of both nucleophiles and electrophiles in one reaction (Figure 1). The chiral properties of the catalysts are derived from the chiral
Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction
Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144
- efficiency. Keywords: metal-organic frameworks; post-synthesis modification; supramolecular catalysis; Introduction Most enzymatic reactions take place in multifunctional cavities in which multiple amino acid residues work cooperatively to orient and activate reactants [1][2][3]. These residues may also
- enhance covalent and/or acid–base catalysis via any combination of non-covalent interactions (hydrogen bonding, π–π stacking, lipophilic interactions, etc) [4][5][6]. Inspired by enzymes, Nature's most efficient catalysts, chemists have long endeavored to synthesize catalytic materials in which multiple
- by increasing the binding affinity for the lipophilic reactants and by decreasing the energy required to desolvate acid/base amino acid catalysts [34][35]. Lipophilicity has also been found to be beneficial in condensation reactions as the removed water molecules are repelled by the hydrophobic
Photoswitches beyond azobenzene: a beginner’s guide
Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143
- and subsequent reduction of 45 (if substrates 43 and 44 contain a NO2 group, this will also be reduced, Scheme 13A) [54], or by Wittig reaction and reduction of the isomeric mixture of alkenes 48 (Scheme 13B) [57]. Oxidation of 49 with oxone [58] or m-chloroperbenzoic acid [54] yields 35. Wittig
- methods for N-arylation depending on the aryl type: electron-rich and electron-neutral substituents are introduced via Chan–Lam coupling with an arylboronic acid, electron-poor aromatics via Cu(I)-catalysed cross-coupling with aryliodonium salts, and monosubstitution is achieved via Ullman–Goldberg
- aldehyde and, if required, N-functionalisation via nucleophilic substitution (for aliphatic substituents) or palladium-catalysed cross-coupling (for aromatic substituents) (Scheme 25) [77]. Hemithioindigo can be synthesised by treating phenylthioacetic acid (83) with triflic acid. Then, the product is
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