Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• using chiral compound 40 with an acid-sensitive protecting group MEM on the alcohol as the precursor, the simple Brønsted acid TsOH successfully promoted the deprotection and dehydration to generate oxa-carbenium 41, which subsequently proceeded the Friedel–Crafts cyclization to furnish

• sarglamides A, C, D and E were established through a concise and protecting group-free approach, which was definitely inspired and utilized by the analysis of the biogenetic pathway of these natural products. Through this approach, a notable amount of natural products were made in one batch. The synthesis

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• bromide 47, followed by Fmoc protection of 56, Boc deprotection of 57, reduction of the NO2 group to NO and intramolecular Mills coupling to form 35h. Removal of the Fmoc protecting group under basic conditions affords the unsubstituted product 35d which, after N-alkylation or acylation affords the

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• attempted (Scheme 2). For this purpose, tert-butyl N-[(1R,2R)-2-amino-1,2-diphenylethyl]carbamate (2h) with an acid-sensitive Boc (tert-butoxycarbonyl) protecting group was prepared in 70% yield from C2-symmetric (1R,2R)-1,2-diphenylethane-1,2-diamine (1) and Boc2O. Compound 2h was then converted to (1S,2S

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

• ][24] (Scheme 1). The proposed strategy relied on the N-deprotection of the intermediate ester 3d inducing O-to-N rearrangement to form amide 5 as a precursor of vinyloxazoline 6. For this purpose, Alloc (allyloxycarbonyl) turned out to be a suitable N-protecting group as it was compatible with the

• analogously from ester R-3d. Thus, Alloc was validated as non-expensive and relatively small N-protecting group, removal of which is compatible with double bond and acetal function of amides S-5 and R-5. The removal of the Pd catalyst at laboratory scale was done by chromatography. For large scale synthesis

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• conducted on the gram-scale starting from indole-3-acetic acid with consistently good yields up to and including the EDC-mediated coupling step. However, the subsequent removal of the Boc protecting group proved more challenging. We observed lower yields during this step, despite screening a range of acids

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

• exploiting the participation effect of the neighboring protecting group [43][44], employing anomeric lactols as acceptors is more complex as lactols with the desired configuration are frequently difficult to obtain (e.g., through anomerization). In addition to the nature of the leaving group and promoter

• of the 2N-protecting group on GlcN- and GalN-derived lactol acceptors proved crucial for the success of borinic acid-promoted glycosylation, as the 2N-Troc-protected acceptor 41 failed to participate in the reaction. In contrast, the 2N-naphthalenesulfonyl (NapSO₂)-protected glucosamine-derived

• /β = 1:1.3), leading to a loss of stereoselectivity and affording the α/β-linked product 59 in 32% yield [40]. The stereodirecting effect of the O-picoloyl protecting group at remote position on the pyranose ring (C3–OH, C4–OH, or C6–OH) in glycosyl donors has been known to induce high facial

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• -naphthylmethyl ether (Nap) protecting group was removed from disaccharide 10 using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in a DCM/H2O (9:1) mixture, giving a 94% yield of disaccharide acceptor 11. To enhance solubility, the trimethylsilyl (TMS) group was selectively added at the less hindered 2-O

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

• carbonyl group, giving 7 in 59% yield. Then, under basic conditions, the aldehyde group in 7 was converted into a vinyl group via Wittig reaction, affording yne-VCP substrate 8 in 90% yield. During this process, the TMS protecting group was lost. We then investigated the [3 + 2 + 1] reaction of 8 and CO

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• ABz 7, Man PVB 8, and Man 9 through orthogonal one-pot glycosylation strategy (Scheme 1B). The 2-O-Bz group in 5–8 served as the neighboring participating group for the stereoselective construction of 1,2-trans-mannosidic bonds, while the 3-O-Lev group in 6 was the temporary protecting group for (1→3

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• efficiently, affording good-to-excellent yields. The Boc-protecting group proved to be stable under the reaction conditions, underlining the importance of avoiding the addition of acidic additives. Steric hindrance exerted a moderate influence on the reaction, and branched aliphatic amines yielded the

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• . The results indicated that the N-protecting group had little impact on the reaction’s efficiency, and various substrates (e.g., methyl, benzyl, isopropyl) were effectively converted to their respective target products 50a–c. Moreover, benzene rings bearing different substituents, whether electron

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

• over 25 steps in 11% overall yield. On the other hand, the efficiency of the process was emphasized by the authors on the utilization of Roche esters 29 and ent-29 to prepare stereochemically pure sulfones 27 and ent-27, respectively. Moreover, the use of the trityl protecting group facilitated a

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

• successfully applied in the synthesis of complex natural products, pharmaceuticals, and functional materials, often streamlining multistep sequences and minimizing protecting-group strategies [50][51]. In 2016, Li and co-workers developed divergent coupling conditions for iminamides 77 with receptor-type diazo

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• ). Efficient EnT catalysis could be achieved with neutral trigonal planar systems 1a–d, while BMIDA substrate 1e was also effective presumably due to the proposed hemilabile nature of the MIDA protecting group in acetonitrile [58]. More electron-donating ligands such as 1,8-diaminonaphthalene (BDAN, 1f) were

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• undergo the decarboxylative cyclization, but also N-mesyl-protected monoester 9f could be converted into 2-aminoproline derivative 6f in 60% yield using a graphite cathode. However, the N-o-nosyl-protecting group is not compatible with the developed electrolysis conditions, likely because it undergoes an

• 13a,d,e in 71–83% yield (Scheme 4). Carboxylic acid 13a could be reacted with glycine benzyl ester in the presence of HATU and Et3N to form dipeptide 16 (66%). In contrast, N-unprotected 2-aminoprolines are unstable and could not be isolated. Thus, the cleavage of the N-Cbz protecting group in 6b

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• -Protecting group optimization for the asymmetric Mannich reaction. All yields were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. aReaction conducted for 24 h. Catalyst screening using 7b as a substrate. All yields were determined by 1H NMR spectroscopy using 1,3,5

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

• ] to obtain free acid 11. Exchange of the Boc protecting group of dimethylaniline 8 to an acryloyl substituent and subsequent saponification furnished dimethylamine building block 13. For the macrocycle assembly, especially the ring closure, we decided on two different routes. While the cryptophycin

• containing a dimethylamino motif did not require an additional protecting group, ring closure was performed through alkene cross metathesis, which has been accomplished reliably and with good yields for other cryptophycins [11][26][27]. However, for the synthesis of a cryptophycin with a monomethylated amino

• group in unit B a suitable protecting group, i.e., allyloxycarbonyl (Alloc), must be used. Since the presence of this allylic double bond would most likely interfere with a clean reaction outcome after alkene cross metathesis, we decided for a more classical ring-closure strategy through

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• host catalysis – (i) using the host as a “protecting group” to direct reactivity external to the host [187][346], and (ii) confinement of a transition-metal catalyst to take advantage of the restricted environment of the host [51][52] – neither of which resembles the enzyme-like possibility of a true

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

• depicted in the review may assist the readers to plan their synthetic protocols in oligosaccharide synthesis. Neighbouring group participation In glycosylation reactions the protecting group at the vicinal C-2 position may be either participating or non-participating in nature. Participating functional

• groups interact with the anomeric carbon and thereby help in the formation of a specific stereocentre. So, modulating the neighbouring protecting group in the C-2 position of glycosyl donors helps in improving the stereoselectivity of the produced glycoside bonds. Ester-type participating protecting

• inversion in carbohydrates was illustrated extensively by Frush and Isbell [75] with silver carbonate as the promoter, drawing analogy with an SN2-type substitution mechanism with the formation of the acetoxonium ion intermediate [76]. An acyl protecting group in the vicinal C-2 position is widely accepted

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

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

• 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

• manipulation to install the C1 sidechain for saframycins, respectively [14][39]. The alkyne segment 8 was prepared by protecting group manipulations in three steps from the known starting material, 2-ethynyl-6-hydroxybenzaldehyde (15), which can be readily synthesized from commercially available 1-bromo-3

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• tertiary amide on the same position. Alternatively, the use of a double Boc-protected Dha resulted in a rather low yield of compound 25 (32%), while varying one Boc-protecting group with a Cbz-protecting group increased the yield substantially to 86% for compound 26. In addition, the use of a cyclic, N-Cbz

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• intramolecular SNAr reactions. Ugi-4CR/deprotection/cyclization (UDC) strategy: In the UDC approach a protected amine and an electrophilic functional group like esters or ketones are used. Convertible isocyanides can also be employed. Once the Ugi reaction is completed, the protecting group is removed, and the

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• = protecting group. Synthesis of β-fluorinated piperidines. Intramolecular fluoroaminations of unsaturated amines published by Li. Intramolecular aminofluorination of unsaturated amines using 1-fluoro-3,3-dimethylbenziodoxole (12). PG = protecting group. 3-fluoropyrrolidine synthesis. aDiastereomeric ratio

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• , Ballester and co-workers reported on the preparation of an octapyridinium-based water-soluble superaryl-extended calix[4]pyrrole molecular container and used it as a capsule for desymmetrization reactions [41], where the reported compound acts both as sequestering and supramolecular protecting group. All of