Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• ][24][25][26][27]. Considering the common steroidal skeleton, we envisioned a chemoenzymatic strategy for the concise synthesis of rhodexin A and the retrosynthetic analysis is shown in Scheme 1. We envisaged rhodexin A (1) could be assembled from two fragments, sarmentogenin (2) and the ʟ-rhamnose

• , an enzymatic C14–H α-hydroxylation of 17-deoxycortisone (5) could be adopted, as described in our recent work [27]. Notably, 5 can be readily obtained from the inexpensive commercial steroid cortisone via a two-step process [27]. Results and Discussion Following the retrosynthetic analysis, we

• natural products. Representative CGs with promising biological activities. Retrosynthetic analysis of rhodexin A and sarmentogenin. Chemoenzymatic synthesis of sarmentogenin (2). Synthesis of rhodexin A. Optimization of the fermentation conditions of the biocatalytic C14–H α-hydroxylation. Supporting

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

• synthetic bottlenecks. Since Nobel laureate E. J. Corey proposed the revolutionary concept of “retrosynthetic analysis” [1], the design of synthetic strategies has built upon this core intellectual framework: starting from the target molecule, a stepwise deconstruction guided by reverse logic leads to a

• either C8 or C10 oxidation, followed by subsequent oxidation state adjustments and functional group manipulations to accomplish the total synthesis of the target natural products [57] (Scheme 11). Based on retrosynthetic analysis of previous routes, they employed common intermediate 103 as the starting

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• relies on a non-photocatalysis approach. Results and Discussion Retrosynthetic analysis of (+)-aglacin B Based on the retrosynthetic analysis shown in Scheme 1, both C8′–C8 and C7–C1 bonds in (+)-aglacin B (2) could be constructed in one-step from the β-bromo acetal 5 by a Ni-promoted tandem radical

• structures of aglacins A, B, C, and E. Retrosynthetic analysis of (+)-aglacin B (2). Synthesis of cyclization precursor 5. Synthesis of (+)-aglacin B (2). Supporting Information Supporting Information File 16: Experimental procedures, characterization data, and copies of 1H/13C NMR spectra

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• toward vibralactone. Impressed by the unexpected biosynthetic pathway, our synthetic strategy also aimed to construct the quaternary center in the late stage. The retrosynthetic analysis of vibralactone (6) is descripted in Scheme 2. Initially, we proposed that vibralactone could be synthesized from

• derivatives with β-lactone moiety. Previous syntheses of vibralactone (6). Retrosynthetic analysis of vibralactone (6). Synthetic study toward vibralactone (6) in the present of β-lactone. C–H insertion utilizing linear precursor 19. Construction the bicyclic skeleton of vibralactone (6) through C–H insertion

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

• centers including one at the bridgehead position. To establish a proper strategy for total synthesis, we could, somehow, design its retrosynthetic analysis through diverse approaches to construct such a bicyclic skeleton. However, inspired by the biomimetic polycyclization of terpenoids, we sought to

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• The retrosynthetic analysis of tricyclic-PGDM methyl ester 4 is shown in Scheme 2. We expected to derive 4 from tricyclic substrate 12 via a side-chain installation at C8 [22]. The spiroketal moiety in compound 12 could be obtained from compound 13 via a diastereoselective spiroketalization dictated

• synthetic strategy toward PGDM methyl ester 4. Retrosynthetic analysis for the first generation synthesis of PGDM methyl ester 4. Synthesis of bicyclic ketal 25. Retrosynthetic analysis for the second-generation synthesis of tricyclic PGDM methyl ester 4. Asymmetric total synthesis of tricyclic-PGDM methyl

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• accessible by this chemistry [25][26], as demonstrated in the formation of the core of the Daphniphyllum alkaloids [27]. The Alstonia alkaloids shown in Figure 1 consist of a bridging nitrogen atom in an azabicyclo[3.2.1]octane that is spiro-fused with an oxindole. A retrosynthetic analysis suggested the

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

• is the retrosynthetic analysis for the key intermediate 1, which can reach the final compound VI via chlorination and demethylation [19]. Target molecule 1 can be accessed by decarboxylation reaction from compound 13, prepared by an intramolecular Heck reaction between the β-ketoester and the vinyl

• reaction in synthesis. Reported biologically active tetrahydrofluorenone-SERMs molecules. Reported synthesis routes to SERMs molecule VI. Lei’s synthesis of natural products of ent-kaurane diterpenoids (A), and natural products songorine, beyerene, garryine and steviol (B). Retrosynthetic analysis for the

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

• precluded the potential issues inherent to one-pot glycosylation based on thioglycosides such as aglycone transfer [43][44][45][61]. Results and Discussion Retrosynthetic analysis Retrosynthetically, we envisaged that glycans 1–4 could be derived from monosaccharide building blocks Man PTFAI 5 and 6, Man

• for the synthesis of tetrasaccharide 2; 3) [1 + 1 + 1] and [1 + 1 + 3] orthogonal one-pot assembly of pentasaccharide 3; 4) [1 + 1 + 1] and [1 + 1 + 1 + 3] orthogonal one-pot assembly of hexasaccharide 4. (A) Glycan structures of PI-88 and (B) retrosynthetic analysis of PI-88 glycan motifs 1–4. One

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• (lit. 155 °C [5]). 1H NMR (300 MHz, CDCl3) δ 5.24 (s, 2H), 6.43 (s, 1H), 6.92–7.04 (m, 3H), 7.09–7.16 (m, 3H), 7.19–7.29 (m, 4H), 7.57 (dd, 3J = 7.7 Hz, 4J = 1.3 Hz, 1H), 7.73–7.83 (m, 2H); MALDI–TOF–MS (m/z): 362.2, [C22H16FNOS + H]+. Retrosynthetic analysis of aroyl-S,N-ketene acetals 1 and tentative

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

• for borrelidin, streamlining the synthesis process. The retrosynthetic analysis by Laschat and co-workers is described in Scheme 12. The target molecule 82 was envisioned to be derived from esters 83 or 86, depending on the chosen synthetic pathway. In route A, ester 83 was designed to originate from

• ]. Application of iterative synthesis of polydeoxypropionate to construct the C3–C11 fragment 60 of borrelidin 1. Retrosynthetic analysis of borrelidin by Yadav et al. [39]. Two-carbon homologation of precursor 66 in the synthesize C1–C11 fragment 61 of borrelidin [39]. Synthesis of the C1–C11 fragment 61 of

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

• convergent approach leveraging an AcOH-interrupted Nazarov cyclization to establish the [5,5,6,6]-tetracyclic scaffold with precise stereochemical fidelity. Results and Discussion Our retrosynthetic analysis toward krishnolides A (7) and C (8) is delineated in Scheme 1B. We hypothesized that these two

• cyclization. Further elaboration of intermediate 10 to krishnolides A and C, as well as other khayanolide-type limonoids is currently ongoing, and the results will be disclosed in future reports. Representative limonoid triterpenes. Structures and retrosynthetic analysis of krishnolides A (7) and C (8

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

• approach will be demonstrated next in the synthesis of simonsol C. Results and Discussion Based on extensive literature investigations, the retrosynthetic analysis strategy for our synthesis of (±)-simonsol C is as follows (Figure 2): The 6/5/6 benzofuran skeleton of (±)-simonsol C can be accessed via an

• valuable for the synthesis of related natural products and their derivatives. Representative sesquineolignan compounds. Retrosynthetic analysis of (±)-simonsol C. The first total synthesis of (±)-simonsol C by Banwell’s group. The second total synthesis of (±)-simonsol C developed by the Qin group. Rapid

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• coupling, and finally leads to the target pheromones by olefin oxidation with RuCl3/NaIO4. Results and Discussion The retrosynthetic analysis of the aggregation pheromone (4R,8R)-1 is shown in Scheme 1. Obviously, the target pheromone (4R,8R)-1 could be synthesized via an oxidation of chiral terminal

• for (4R,8R)-1, the other constituents of the aggregation pheromone (4R,8S)-1, (4S,8R)-1 and (4S,8S)-1 could be prepared. Based on the retrosynthetic analysis of the aggregation pheromone (4R,8R)-1, our synthesis began with the preparation of chiral tosylate (S)-10 (Scheme 2). The ring-opening reaction

• tosylate and a chiral Grignard reagent. The synthetic pheromone could be valuable for the control of the red flour beetle. The aggregation pheromone of Tribolium castaneum. Retrosynthetic analysis of the aggregation pheromone (4R,8R)-1. Synthesis of chiral tosylate (S)-10. Synthesis of chiral tosylate (R

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• corniculatolides or isocorniculatolides. 2.2 Retrosynthetic analysis Due to the aforementioned biological activities and the low availability from natural sources to provide sufficient material for additional investigations, the combretastatin D series and their isomeric macrolides have become an attractive target

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• for biological screening. The era of scalability [2] in total synthesis prompts researchers in this field to make use of more direct retrosynthetic disconnections with the aid of “radical” retrosynthetic analysis, as the advancement in the area now allows to harness one-electron power in a highly

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• . Impressed by the structural features and biological profiles, our group embarked a project on the total synthesis of this natural product. Herein, we report our stereoselective synthesis of its 6-5-5 tricyclic skeleton. Our retrosynthetic analysis is shown in Scheme 1. For the formation of the D ring with

• natural product aberrarone from the key intermediate cyclopentenone 8 is currently underway, and will be reported in due course. Selected representative natural products with 6-5-5 tricyclic skeleton. Retrosynthetic analysis of aberrarone (1). Synthetic study toward aberrarone (1). Supporting Information

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ]phenanthridine derivatives and further assessments of their bioactivities are currently in progress in our laboratory. Classification of benzo[c]phenanthridine alkaloids. Representative synthetic strategies for macarpine (1). Retrosynthetic analysis of marcarpine precursor 12 for a partial synthesis. Syntheses

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• . Preparation of racemic 3-propylnorleucin 16a. Unsuccessful direct coupling of amino acid methyl esters with the benzothiazine motif and retrosynthetic analysis of alternative linear reaction routes. a) Synthesis of 2H-benzo-1,4-thiazine amino acid conjugates 19a and 19b and b) 3D renderings of 19a and 19b

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• stereoselective glycosylations. The work provides an access to the trisaccharide repeating unit of the O-polysaccharide of Providencia stuartii O49 with the stereospecific α-p-methoxyphenyl glycoside. Structure of the repeating unit of the lipopolysaccharide of Providencia stuartii O49 serotype. Retrosynthetic

• analysis for the synthesis of the target trisaccharide 1. Synthesis of the monosaccharide building blocks 3, 6, and 7. Linear synthesis of trisaccharide derivative 2. Synthesis of ᴅ-galactose donor 12. One-pot synthesis of trisaccharide derivative 2. Synthesis of trisaccharide derivative 1. Supporting

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• design new synthetic methodologies for reproducing these natural products and their analogues as well as to develop new pharmaceuticals from them. Structures of brevipolides A–O (1 – 15). Retrosynthetic analysis of brevipolide H (8) by Kumaraswamy. Attempt to synthesize brevipolide H (8) by Kumaraswamy

• . (R,R)-Noyori cat. = RuCl[N-(tosyl)-1,2-diphenylethylenediamine)(p-cymene)]. Attempt to synthesize brevipolide H (8) by Kumaraswamy (continued). Retrosynthetic analysis of brevipolide H (8) by Hou. Synthesis ent-brevipolide H (ent-8) by Hou. Retrosynthetic analysis of brevipolide H (8) by Mohapatra

• . Attempt to synthesize brevipolide H (8) by Mohapatra. Attempt to synthesize brevipolide H (8) by Mohapatra (continued). (+)-(IPC)2-BCl = (+)-B-chloro-diisopinocampheylborane. Retrosynthetic analysis of brevipolide H (8) by Hou. Synthesis of brevipolide H (8) by Hou. Retrosynthetic analysis of brevipolide

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• parameters are drawn at 50% probability level. Molecular structure of compound 17a, displacement parameters are drawn at 50% probability level. Retrosynthetic analysis of heterocycles A and B. Free-radical cyclization of N-protected and N-unprotected pyrroles 1a and 2. Synthesis of 2H-pyrido[2,1-a]pyrrolo

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• resulting from the low stability of amino sugar hemiacetals. The prepared polyfluorinated thiodonors and hemiacetals are valuable intermediates in oligosaccharide synthesis and their utility in glycosylation is currently being studied in our group. Retrosynthetic analysis of the target fluoro analogs

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• introduction of a tetrahydroquinoline moiety by direct amination to triflate 7. Retrosynthetic analysis of the pyrrolo[2,3-c]quinoline ring construction. Synthesis of N-substituted 4-aminopyrrolo[3,2-c]quinoline 18. Synthesis of the tetrahydroquinoline moiety through cycloamination. Synthesis of trigonoine B

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• approach to 9,11-secosterols is depicted in the retrosynthetic analysis in Scheme 1. There are two key steps in obtaining the skeleton of the secosterol. The first is (di)hydroxylation at C9 (C11), and the second is C9–C11-bond cleavage, which can be carried out by a well-developed chemical oxidation of

• ; HRMS (m/z): [M + H]+ calcd, 317.1747; found, 317.1755. A) Tetracyclic core of steroids and possible sites of bond cleavages for secosteroids. B)The first 9,11-secosteroid isolated in 1972 [7]. Retrosynthetic analysis of 9,11-secosterols. Synthesis of starting materials. Reagents and conditions: i