Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• functionalization of one hydroxy group, offers beneficial procedures for accessing diverse structural motifs. In this review, we highlight a curated compilation of publications, focusing on the applications of enantioselective desymmetrization of prochiral 1,3-diols in the synthesis of natural products and

• intramolecular cyclization of 16 generated benzofuran 17 in 83% yield. After protecting the phenolic hydroxy group of 17, cross-metathesis (CM) with allylic alcohol 18 catalyzed by 13 furnished intermediate 19. Desilylation of 19 produced heliannuol G (20) and heliannuol H (21), with the structure of 21

• enantioenriched monoester 53 in hand, the synthesis proceeded toward fredericamycin A (60) (Scheme 9). Dione 55, which was prepared from 53 in six steps, underwent addition with alkyne 56 followed by acylation of the resulting hydroxy group with compound 57 to yield ketone 58. A subsequent seven-step

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• planarly chiral paracyclophanes [39]. Commenced with a macrocyclization precursor 36 featuring both a hydroxy group and an allenamide moiety, the CPA-catalyzed asymmetric intramolecular addition led to the successful construction of planarly chiral macrocycles 37 (Scheme 10). This method demonstrated broad

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• the amine group would function as the catalytic unit for the Knoevenagel reaction, while the hydroxy group would serve as a handle through which we would tune the lipophilicity of the catalyst. Recently, we found that isopropyl isocyanate reacts preferentially at the DPG hydroxy groups of KSU-1 [46

• with isopropyl isocyanate and tert-butyl isocyanate required 3 and 4 hours respectively to achieve complete conversion at the hydroxy group without any amine reaction. With n-hexyl isocyanate and tetradecyl isocyanate, reaction at the amine was observed after just one hour, before complete conversion

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• , Pd scavengers have to be considered at the work-up. Unsaturated amides trans-S-5 and trans-R-5 were transformed to oxazolines S-6 and R-6 in good yields by mesylation of the hydroxy group (Scheme 5). Having both enantiomers in hand, the enantiomeric excess of oxazolines S-6 and R-6 was determined by

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• system, a variety of other factors commonly influences both the reaction rate and the stereochemical outcome of the glycosylation reaction, including the reactivity of the acceptor hydroxy group, the effect of remote protecting groups and a balance between the nucleophilicity of the acceptor and the

• anomeric configuration of the lactol acceptor is particularly challenging when the desired form is not thermodynamically favored, as is the case with β-mannose derivatives. A refined strategy employing cyclic stannanes to lock the anomeric hydroxy group of a mannose-derived lactol in the equatorial

• ]. Diarylborinic acids have been shown to provide exclusive catalytic performance in the site-selective monofunctionalization of various 1,2- and 1,3-diols [60], as well as in the regioselective glycosylation of polyhydroxyglycosyl acceptors via base-promoted deprotonation of a specific hydroxy group involved in

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• % yield with a cyclopropyl group. Then reducing the carboxylate group in 4 with DIBAL-H afforded alcohol 5 in 67% yield. Next, Sonogashira coupling reaction between 5 and trimethylsilylacetylene generated 6 with an alkyne moiety quantitatively. After that, the hydroxy group in 6 was oxidized into a

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• Nozaki–Hiyama–Kishi reaction and a one-pot Prins cyclization/transannular hydride transfer to construct the 5-8-5 tricyclic scaffold. Enzymatic oxidations were used to install the hydroxy group at the C-3 position. Ten fusicoccanes were synthesized in 8–13 steps each. Despite these efforts, a strategy

• cotylenin A and cotylenol (Figure 3a). Oxidation of brassicicene I with Dess–Martin reagent afforded intermediate 9 in 92% yield. The tertiary hydroxy group of compound 9 was further protected with a TMS group to provide compound 10 in 90% yield, a key intermediate in the synthesis of cotylenol and

• cotylenin A by Nakada and co-workers [21]. However, installing the C9 hydroxy group requires the use of stoichiometric MoOPH [39], which raises toxicity and safety issues. Therefore, we sought an enzymatic method to selectively oxidize 5 at the C9 position. Dairi and co-workers reported that Orf7 oxidizes

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• )quinolin-7-ol (2) Diazotization of pentafluoroaniline has been recommended to be carried out in nonaqueous media or concentrated mineral acid, otherwise the coupling product always contains a hydroxy group on the perfluorophenyl ring at the position para to the azo group. It appears that when solutions of

• the diazonium salts are made alkaline the para-fluorine atom is so readily replaced by a hydroxy group, and that the 4-hydroxy-2,3,5,6-tetrafluorobenzene cation is the entity formed first [90][91]. A 50 mL round-bottomed flask equipped with a mini magnet was charged with pentafluoroaniline (0.64 g

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• condensation product, compound 2. Compound 1 is proposed to further undergo a dehydration reaction by the elimination of the α-proton and β-hydroxy group of the threonine residue to form compound 3. Compound 4 is a product of methylation of 3 carboxyl functionality (see Figure 4). These compounds are possibly

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• epoxidation and regioselective reduction to install the hydroxy group at the C3 position [39]. In their retrosynthetic analysis, the target molecule 61 was envisioned to be obtained from epoxide 63 through regioselective opening of the epoxide ring, oxidation of the resulting primary alcohol to a carboxylic

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• the reduction of amide-generated ketone 12 after a subsequent Dess–Martin oxidation. Upon treatment of 12 with Co(acac)2 and PhSiH3 in iPrOH at 80 °C, the Mukaiyama hydration of enamide delivered hemiaminal 13. Despite the incorrect configuration of the newly formed hydroxy group, it is considered

• a fragmentation process for the total synthesis of (−)-phlegmariurine B. A one-pot epoxidation/nucleophilic epoxide opening introduced both a hydroxy group and a chloride across the cyclopentene, producing 14 in 57% yield. After oxidation of alcohol 14 to ketone 15, the Mukaiyama hydration then

• photocyclization. This transformation was carried out using a high-pressure mercury vapor lamp to afford benzazepine 22, completing the construction of the pentacyclic framework of the natural product. Subsequent functional group manipulations, including the Chugaev elimination of the hydroxy group on the

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• simultaneously installing the hydroxy group at C30. The latter intermediate could in turn be derived from dienone 11 by an AcOH-interrupted Nazarov cyclization [32][33][34], thereby establishing the B ring with the desired all-cis stereochemical configuration, including the quaternary carbon at C10 and the

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• the hydroxy group to form complex Int-17 and the amino group undergoes nucleophilic attack to generate Int-18. After CO insertion complex Int-19 is produced and reductive elimination ultimately affords the indolo[3,2-c]coumarin product 10. In 2023, the Garg group achieved the first example of

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• fluorophore derivatives bind the Pepper aptamer with affinities in the low nanomolar range [12]. Crystal structure analyses revealed that in the ligand binding pocket, a characteristic hydrogen bond is formed between the hydroxy group of the N-hydroxyethyl substituent of HBC and the N7 of G41 [12][13]. We

• monitored by the inherent fluorescent signal of the target RNA [11]. The synthetic route to such an HBC fluorophore is shown in Scheme 6. Piperidine-induced condensation of compound 2 with 4-iodophenylacetonitrile afforded the HBC-like ligand, whose hydroxy group was immediately protected with TBS-Cl to

• -dimensional structure of the Pepper binding site with a bound HBC derivative (pdb code 7EOM). The hydrogen bond between N7 of guanine in position 41 (G41) and the hydroxy group of HBC is highlighted as gray dashed line [12]; d) concept for covalent attachment of HBC fluorophores to the N7 atom of G41 of the

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• when a fluorine atom is introduced vicinal to the hydroxy group (Figure 8). As was seen with ethers (I, Figure 7), there is again a subtle preference for the O–C–C–F motif to adopt a gauche conformation [44]. This is attributable in part to the hyperconjugation phenomenon (I, Figure 8). In several

• molecules’ intermolecular interactions too. The intramolecular H-bond makes the hydroxy group a weaker intermolecular H-bond donor [104] (e.g., 55 vs 54, Figure 8). This runs counter to a longstanding assumption [105] that the inductive effect of fluorine should always make the hydroxy group a stronger H

• -bond donor. For non-rigid molecules, the greater the population of intramolecularly H-bonded conformers, the worse the hydroxy group will be as an intermolecular H-bond donor [106]. To be clear, fluorine can make the hydroxy group a stronger intermolecular H-bond donor in certain circumstances, for

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• -carbonyl group was linked through an ester bond and the only hydroxy group available for this esterification was the one at C-7. This compound was finally elucidated as massarilactone D 3,4-di-O-methacryloyl-7-O-(6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2-carbonyl). For the formation of compound 2, an

• oxa-Diels–Alder reaction between two methacryloyl chloride molecules could have taken place to yield 6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2-carbonyl chloride as previously described [18] before esterification of the hydroxy group at C-7. Compounds 3 (6% yield) and 4 (90% yield) were obtained

• , Ha-11) and 5.23 (d, J = 3.0 Hz, Hb-11) characteristic of exo-methylene protons as in massarilactone H [13][21], suggesting an exo-dehydration of the C-7 hydroxy group. This was further supported by resonances depicted at δC 148.8 (C-7) and 94.3 (C-11). Since compound 3 is massarilactone H 3,4-di-O

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• DIPEA, affording compound 17 with an 89% yield [11]. For the following alkylation step with tert-butyl bromoacetate, three bases were tested: potassium carbonate, cesium carbonate, and sodium hydride. Considering the targeted alkylation of a phenolic hydroxy group and the pKa requirements of this

• alcohol 19 was isolated in 89% yield. The copper-catalyzed replacement of the bromine substituent in 19 with a hydroxy group was achieved in the presence of a catalytic amount of oxalamide ligand I [13]. This transformation is critical for enabling further functionalization and the reaction conditions

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• conjugable payloads by our group. Modifications of unit B with conjugation handles are scarcely explored and mainly include the exchange of the para-methoxy group (Figure 1B). The sole exchange of the para-methoxy group of cryptophycin-52 (IC50 = 22 pM) by a hydroxy group reduces the cytotoxicity by

• approximately only one order of magnitude (IC50 = 0.52 nM) when tested on CCRF-CEM T lymphoblasts [20]. Loss of the meta-chloro substituent shows a similar trend. Functionalisation of the hydroxy group with ethylene glycol residues further decreases cytotoxicity, whereby this effect increases with increasing

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• . First, the alkyl handles bearing a primary hydroxy group were introduced and then converted into the electrophile of choice. More specifically, to furnish compounds 4b–d, precursor 9 was treated with the corresponding amino alcohols in the presence of a desiccant. The imines formed were subjected to

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• product on HPLC even for the reaction of diethylene glycolamine and 1. Capping the free hydroxy group with a methyl group improved the separation on HPLC marginally. However, incorporating a clickable propargyl group greatly benefited separation. Similar to the alcohol, amino-PEG5-acid also reacted with 1

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• room temperature was the only difference with the pivaloyl group. Protecting the C-2 hydroxy group as ADMB ester yielded 1,2-trans glycosides in high yields. However, its participating mechanism is still unclear. So, we reserve our views on placing the use of ADMB as potential neighbouring group

• ether-type chiral auxiliary group for protection of the hydroxy group in the C-2 position was devised by Boons et al. in 2005 which opened a new avenue in oligosaccharide synthesis. Auxiliary group indicates a substituted ethyl protection which has a nucleophilic centre that can donate electrons in the

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• tropolone ring proton, which appears at 6.9 ppm. A characteristic specificity of the 1H NMR spectra of compounds 7 and 8 is the presence of signals of hydroxy group protons forming a strong hydrogen bond with the indoline nitrogen atom, which closes the six-membered chelate cycle. These signals are observed

• in the weak field at 15.2–15.8 ppm for 7a,b and 14.3–14.8 ppm for 8a,b, respectively, as a broadened singlet peak. A dynamic equilibrium of tautomeric forms 7, 8 (OH)–7, 8 (NH) exists in solution, which can be detected by the broadening of the hydroxy group proton signal in the 1H NMR spectrum

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• ketocarbonyl carbon at δC 192.9 (C-1') confirming the presence of a hydroxy group at C-3' and to be as depicted in Figure 1. Further key HMBC correlations were recognized including those from an olefinic proton at δH 5.51 (d, J = 9.6 Hz, H-11) to one allylic methyl group at δH 1.77 (d, J = 1.2 Hz, H3-16) and

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• antitumor activity, triggered by DNA alkylation [6][7][8]. The aminonitrile/hemiaminal at C21 generates an iminium cation while releasing a cyanide or a hydroxy group under physiological conditions. This iminium cation facilitates nucleophilic attack by guanine residues in the minor groove of the GC-rich

• three base pairs, predominantly 5’-GGC-3’ and 5’-GGG-3’ [12][13]. Notably, a bis-phenol type unnatural analog 3, composed of the C5 deoxy A-ring bearing a phenolic hydroxy group at C8, presumably as a HB donor upon interaction with nucleic acids, exhibits superior DNA alkylation capability compared to

• thermodynamically more stable than its 5-exo counterpart 13. Thirdly, the 2,3-diaminobenzofuran would be utilized as a temporary protecting group for both the phenolic hydroxy group and the nitrile moiety. These functional groups are necessary for the aromatic A-ring to interact with DNA and for synthetic