Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• as “illisimonane skeleton”. The absolute configuration of (−)-illisimonin A was determined to be 1R,4R,5R,6R,7S,9S,10S by comparing the calculated electronic circular dichroism (EDC) spectrum with experimental CD data (Figure 2). Biological evaluation revealed that illisimonin A exhibits

• Rychnovsky [28], Kalesse [29], Yang [30], Dai [31] and Lu [32] have achieved the total synthesis of this molecule. Notable, Rychnovsky and co-workers revised the absolute configuration of (−)-illisimonin A to 1S,4S,5S,6S,7R,9R,10R. This review summarizes the reported synthetic routes toward illisimonin A

• , including uncompleted approaches. Review Rychnovsky’s synthesis and the absolute configuration revision of (−)-illisimonin A In 2019, Rychnovsky’s group reported the first total synthesis of illisimonin A [28]. Recognizing that the strained trans-pentalene moiety in the molecule is challenging to construct

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• limitations in technical capabilities at the time, its absolute configuration remained undetermined. Over the subsequent two decades, its hydrolysis product ryanodol (4) and several structurally related analogs were isolated sequentially [9][10][11][12][13][14]. The absolute configurations of both 1 and 4

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• enantiomers of 51 allowed Tsukano and co-workers to prepare both enantiomers of complanadine A. Their further biological evaluation of the complanadines and several synthetic intermediates revealed that the pseudo-dimeric structure, absolute configuration, and oxidation level are important for the observed

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• all compounds. In this study, we developed a method to determine the absolute configuration of the terminal MPO moiety with high accuracy and sensitivity by a combination of chemical degradation, chemical synthesis, and chiral LC–MS analysis. The applicability of this method was demonstrated through

• typically determined using NMR-based techniques, such as coupling constant analysis and NOE experiments, sometimes with the aid of computational chemistry [3][4][5][6][7]. In contrast, absolute configuration remains more challenging to determine, as it frequently requires chemical degradation or

• groups. Total synthesis is a powerful approach for determining absolute configuration through the comparison of specific rotation or chromatographic behavior; however, it requires considerable time and effort. In this context, we have been working on developing effective approaches to determine the

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• conformers, obtained via DFT calculations, show a correlation with both the sign and intensity of the experimentally observed CD spectra. Keywords: absolute configuration; chiral amine; chiral quaternary ammonium salt; circular dichroism; DFT calculation; Introduction Determining the absolute

• effect in CD, the direction of twist can be estimated. The absolute configuration of amines can be determined by comparing the direction of the twist determined by CD with that obtained by conformational analysis using theoretical calculations. However, this method has only been applied to simple primary

• 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

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• . Additionally, there is a lack of corresponding pharmacological activity studies. In 2021, the group of Han completed the first enantioselective total synthesis of (+)-toxicodenane A (16) and determined its absolute configuration by employing an early-stage desymmetric enantioselective reduction of a 1,3

• Prins cyclization produced the oxa-bridged product 88. Finally, ozonolysis of 88 followed by Wittig reaction of the resultant ketone and subsequent reduction accomplished the total synthesis of (+)-toxicodenane A (16). The authors eventually confirmed that the absolute configuration of (+)-16 was 4S,5S

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

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• absolute configuration was unambiguously determined by the comparison with the reported compound chaetominine (1)” [32]. The only information regarding the absolute configuration mentioned in the text is as follows: “aspera chaetominine A (1) was presumably biosynthesized from ʟ-isoleucine, ʟ-valine

• (–)-isochaetominine C (6), whose absolute configuration is tentatively assigned as 2R,3R,11S,14R. It is worth noting that compound 13 has been obtained in our previous investigation [63]. However, the 1H and 13C NMR spectra were recorded in DMSO-d6 which prevent a direct comparison with the data of aspera

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• with a Daicel Chiralpak IF column (Figure S1, Supporting Information File 1). The absolute configuration of the separated enantiomers of MC1 was determined based on the calculated CD spectra (Figure S4, Supporting Information File 1). The first fraction was defined as the (+)-enantiomer, and the second

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• absolute configuration of the piperazine formed, a pure sample of compound 2b derived from (1R,2R)-trans-diaminocyclohexane was crystallized from a chloroform solution resulting in the formation of white crystals suitable for single crystal X-ray diffraction studies. The absolute configuration of the

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• observed between the dimer and trimer, despite the same absolute configuration of the planar chiral [2.2]paracyclophane units, which was reproduced by theoretical studies. Keywords: circularly polarized luminescence; oligomer; [2.2]paracyclophane; planar chirality; Introduction Cyclophane is a general

• same absolute configuration. The |glum| value of 7 was 0.4 × 10−3 (Figure S18A, Supporting Information File 1), which was lower than that of 6. In the case of the film states of 6 and 7, low PL brightness and intermolecular random orientation of fluorophores resulted in noisy CPL signals. The CD

• | values of the ordered of 10–4–10–3. The chiroptical properties of dimers and trimers showed opposite Cotton effects and CPL signals, despite the same absolute configuration of the planar chiral [2.2]paracyclophane crossing points. The π-conjugation system of the dimer that exhibited CPL was highly curved

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

• the biogenesis of this heterocyclisation leading to the pseudomonine biosynthesis [23]. The absolute configuration of the threonine residue in compounds 1 and 2 was assigned as ʟ, based on the derivatization of 1 and 2 hydrolysates with ʟ-FDAA, a Marfey’s reagent, followed by chromatographic profiling

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

• a cancer therapeutic, exhibiting anti-inflammatory, anti-angiogenic, antimicrobial, antifungal, and antimalarial activities. While Keller-Schierlein first determined its chemical structure, Anderson later confirmed its absolute configuration using X-ray crystallography [16]. During the screening of

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• phosphate complex. Relative energies (in kcal·mol−1) at B3LYP/6-31G* for different pathways involving the configuration-determining hydrocyanation step. Absolute configuration (R or S) refers to that in hydrocyanation product 10. Supporting Information CCDC 1824279 (4), CCDC 1824280 (3), and CCDC 1824281

• of alcohols as additives has a negative effect on both yield and enantioselectivity. The enantioselectivity was generally low (Table 2, entries 4–9) and with preference for the S-configured hydrocyanide employing the pre-formed Ca complex 6. In addition, product 2 was obtained with absolute

• configuration opposite to the results with in situ-formed Ca complex 6, for which BINOL phosphate was newly synthesized, instead of purchased, and with which we achieved much higher ee values (87–89% ee (R), Table 2, entries 1–3). These distinctly different outcomes, when methods to generate Ca complex 6, or

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• that the enantiomeric ratio values in Table 5 correspond to the major anti-diastereomer. The absolute configuration of the significant diastereoisomer obtained in the kinetic resolution of compound 3 was established by chemical correlation with (2R,3S)-1,2,3-triphenylpentan-1-one (19), previously

• of 18 with Raney nickel in ethanol at room temperature gave a 3:1 mixture of anti/syn-19. The absolute configuration of anti-19 is (2R,3S), indicating that in the resolution process, the major enantiomer corresponds to the anti-(3S,4R)-5-oxo-3,4,5-triphenylpentanal. Having established that the major

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

• groups ascribed to H3-14 and H3-15 together with a diastereotopic methylene group at δH 1.25/1.36 (H2-13) confirming the depicted end of the aliphatic sidechain as –C(CH3)=CH-CH(CH3)-CH2-CH3 similar to that in farinosones A/B [8] and tenellin derivatives [10][11]. To establish the absolute configuration

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• /bjoc.20.267 Abstract A new psammaplysin derivative, ceratinadin G (1), was obtained from the Okinawan marine sponge Pseudoceratina sp., and the gross structure was clarified through spectroscopic and spectrometric analyses. The absolute configuration of compound 1 was established by comparing its NMR

• derivatives exhibit a range of bioactivities, including antibacterial, anticancer, antimalarial, and antiviral effects. Since the discovery of the first psammaplysin derivative, psammaplysin A [4][5], these alkaloids have been recognized as challenging targets for total synthesis. The absolute configuration

• , the first asymmetric total synthesis of psammaplysin A was accomplished by Smith and Morrow, and the absolute configuration of compound 1 was also confirmed through organic synthesis [7]. In our ongoing research focused on uncovering new bioactive secondary metabolites from Okinawan marine sponges, we

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• LiOH, followed by a coupling reaction with ʟ-valine methyl ester hydrochloride, to give the corresponding four enantiomerically pure tripeptides 8 with satisfactory yields over two steps (Scheme 6). The absolute configuration (S,S,S) of the isomer 8f was unambiguously assigned by X-ray crystallographic

• analysis (Figure 5). Consequently, it was possible to assess the stereochemistry of the other diastereoisomer 8f’ and their precursors 7f and 7f’. On the other hand, considering the similarities of the 1H NMR spectra of the CF2H and CF3 analogs, by comparison, we could hypothesize the absolute

• configuration of compounds 7e and 7e’ and consequently of tripeptides 8e and 8e’ (see Supporting Information File 1). Next, some preliminary conformational studies were performed. Firstly, the X-ray crystallographic analysis of compound 8f did not show any hydrogen-bond pattern and the global structure of the

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• , followed by a Conia-ene cyclization. The absolute configuration of the products is controlled by the ligand, which further confirms the remote stereocontrol of the copper catalyst. They obtained a single crystal of dinuclear copper and confirmed that the catalytic efficiency of the single crystal is

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• -diastereomers [34]. Unfortunately, the absolute configuration of these compounds could not be determined due to the small amounts available. Diketopiperazines can be formed either enzymatically or non-enzymatically, e.g., by heat dimerization of amino acids [35]. Both antibacterial and antifungal activities

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• , therefore we were compelled to proceed directly to the next step. Cleavage of the 1,6-anhydro bridges was achieved under acetolysis conditions providing halogenated talopyranoses 12–15 in good yield over 3 steps as α anomers. Luckily, inter-halides 13–15 were crystalline, allowing the absolute configuration

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• as in isoaltenuene [251] had to be corrected after total synthesis [249] and comparison of measured and calculated ECD spectra [162]. The revised absolute configuration of (−)-altenuene is given in Figure 14. Altenuene was isolated in various Alternaria spp., i.e., not only in A. alternata, but

• and was given the name ‘5’-epialtenuene’ (56) following the numbering in the biphenyl substructure [268]. Although no data on the absolute configuration are given in the initial and in most of the following reports, it turned out that 56 can be found in both enantiomeric forms, where the data are

• absolute configuration as given in Figure 14 (with a tiny caveat concerning the sign of the specific rotation of 56). A specific rotation of 56 was furthermore given only once when (+)-56 was isolated from an unidentified freshwater fungus [251]. 5’-Epialtenuene with non-specified chirality was furthermore

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• on a 1 mmol scale under the optimized reaction conditions (Scheme 4). The product 3aa was isolated in slightly lower yield and similar enantioselectivity compared to the 0.2 mmol scale reaction. Subsequently, we turned our attention to determine the absolute configuration of the newly formed chiral

• crystallography data of ent-3ba (Figure 2) [37]. The stereochemistry of the products in this series was assigned by analogy. Based on the observed absolute configuration of product ent-3ba and preceding literature reports [38][40], a plausible mechanistic pathway is outlined in Scheme 5. Initially, in the

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• residual water during column chromatography. Unfortunately, attempts to assign the absolute configuration of products 5 failed, as we have not been able to obtain any crystals suited for single crystal X-ray diffraction analysis. Finally, we also tested the suitability of products 5 to access acyclic α-AA

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• from different strains of bacteria only retain the sequences from one of the sources. For example, only the erythromycin PKS from Saccharopolyspora erythraea were retained. (b) To associate sequence information with reliable absolute configuration of the product, the stereochemical configurations of