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

• tertiary enamides as cyclization precursors (Scheme 6). The analogous polycyclization generated a tetracyclic N-heterocycle with three continuous stereogenic centers, one of them being an aza-quaternary carbon [31]. The resulting fused ring-system structurally resembles the nucleus of erysotramidine

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

• tricyclo[4.2.110,30.11,4]decane ring system. Additionally, krishnolides A and C contain 9–11 stereogenic centers and exhibit diverse oxidation patterns. Their relative and absolute configurations were determined through NMR, HRESIMS and ECD experiments, as well as single crystal X-ray diffraction analysis

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• crucial advancement in this field. In particular, a key objective is developing regio-, diastereo-, and enantioselective allylic substitution reactions that can effectively construct enantioenriched stereogenic centers from either allylic electrophiles or organometallic nucleophiles [39][40]. This

• consistent stereochemical outcome highlight its practical utility. Their subsequent work with chiral tertiary boronic esters 25 revealed an effective strategy for constructing quaternary stereogenic centers through allylic substitution reactions (Scheme 8) [48]. By employing in situ-generated

• bearing quaternary stereogenic centers with high stereospecificity. This methodology represents a significant advancement in the construction of challenging all-carbon quaternary stereogenic centers through stereospecific allylic substitution reactions. To elucidate the origin of the selective boron group

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

• , which formed the corresponding products in high to excellent enantioselectivities. In this paper, the asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon stereogenic centers by the Mannich reaction through chiral halonium salt catalysis is presented, which provided the

• corresponding products in excellent yields with up to 86% ee. To the best of our knowledge, the present paper is the first to report the asymmetric construction of β-amino cyanoesters with contiguous tetrasubstituted carbon stereogenic centers by the catalytic Mannich reaction. Keywords: asymmetric catalysis

• alcohols [38]. In this context, their asymmetric syntheses are important and have also been researched mainly using chiral catalysts [39][40]. Previously, the Mannich reaction has been applied in the construction of contiguous stereogenic centers (Figure 2). In 2005, Jørgensen and co-workers reported the

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• 20 is afforded through protonolysis, regenerating the active copper species to complete the catalytic cycle. 2 Amidation via oxidative insertion to N–O bonds and reductive elimination 2.1 Hydroamidation of vinylarenes Amines bearing stereogenic centers have been widely investigated in the research

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• phosphoric acid-catalyzed enantioselective [4 + 2] cycloaddition of benzothiazolimines 21 and enecarbamates 45 [41]. With this novel methodology benzothiazolopyrimidines 47 bearing three contiguous stereogenic centers were synthesized in good to excellent yields (58–98%), complete diastereoselectivities and

• + 3) cycloaddition of 3-alkyl-2-vinylindoles 59 and azoalkenes 53 (Scheme 22). This methodology afforded chiral pyrroloindolines 60 bearing two tetrasubstituted stereogenic centers in good yields (61–96%) and excellent stereoselectivities (all >95:5 dr, 86–99% ee) by using chiral phosphoric acid XVII

• enables the synthesis of benzofuran-fused tetrahydropyridines 62 bearing three contiguous stereogenic centers in good yields (80–99%), and excellent diastereoselectivities (>20:1 dr) and good to excellent enantioselectivities (63–99% ee) [45]. In general, good enantioselectivities were obtained with all

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

• strategic approach allows precise control of the stereogenic centers at the C3-position during cyclization (Scheme 16). Ugi-4CR/metal-catalyzed reaction: The fusion of MCRs with cross-coupling reactions represents an attractive approach as a result of the increased intricacy and effectiveness [62]. Moreover

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• yield (78% vs 96%) was observed upon scaling up. In the case of products with two stereogenic centers (3r–t), the formation of a single trans-diastereomer was observed. According to literature data, the vicinal coupling constants in the 3,4-disubsituted β-lactam cycle have characteristic values for the

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• correlations linking three different fragments. Compound 1 features three stereogenic centers at C-2, C-3, and C-16. The relative configuration of C-2 and C-3 was determined as (2R*,3R*) by 1H-1H NOESY correlations (Figure 3), while the relative configuration of C-16 remains unresolved due to the

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• stereogenic centers in compound 1 as 1R, 2R, 3R, 6R, 7R, 8S. This is likely the first characterized crystal structure of an ovalicin-type sesquiterpenoid. The molecular formula of pseudallene B (2) was assigned as C15H26O5S (three unsaturations), with one CH2 unit less than 1, based on positive HRESIMS data

• of 0.048(7), which suggested all the stereogenic centers in compound 2 as 1R, 2R, 3R, 6R, 7R, 8S. In addition to compounds 1 and 2, three related ovalicin-type sesquiterpenoid derivatives 3 [10], 4 [11], and chlovalicin (5) [12][13] were isolated and identified from the fungus P. boydii CS-793. It

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• . Asymmetric anion–π catalysis of intrinsically disfavored exo-selective Diels–Alder reactions on fullerene catalyst 21, with notional endo and exo transition states VI and VII, respectively. Asymmetric anion–π catalysis to install remote stereogenic centers on fullerene catalyst 21, with notional transition

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• -workers [61] extended the application of NHC–copper catalysts to the conjugate addition of boronates to acyclic α,β-unsaturated carboxylic esters, ketones, and thioesters leading to the enantioselective formation of boron-substituted quaternary carbon stereogenic centers (Scheme 43). All transformations

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• last step involves the enamine intermediate which drives an intramolecular aldol condensation to form the final product 5. In this elegant cascade process, catalyst 1 promotes three consecutive carbon–carbon bond forming steps generating four stereogenic centers with high diastereoselectivity and

• simple flash chromatography. Conclusion An unprecedented methodology for the synthesis of 4,6-disubstituted 5-nitrocyclohexene carbaldehydes with three contiguous stereogenic centers using acetaldehyde as one of the reaction components of an Enders cascade reaction has been developed. The masked form of

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• construction of stereogenic centers using polar organometallics [1]. In this way, 1,4-additions of typical organometallics such as dialkylzinc, Grignard reagents, and trialkylaluminum have been developed [2][3][4][5][6][7][8][9]. Recently, also Cu-catalyzed conjugate additions of organozirconium [10][11] or

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• . Application in total synthesis As shown before, asymmetric tandem conjugate additions followed by enolate trapping are robust methodologies for synthesizing complex structures with multiple stereogenic centers. For this reason, such stereoselective procedures are commonly used in total synthesis (Figure 2

• contains six contiguous stereogenic centers out of which four are all-carbon quaternary stereocenters. The authors have achieved the stereoselective synthesis of waihoensene for the first time with a 3.8% overall yield (15 steps) (Scheme 59). The construction of the triquinane core included a Cu-catalyzed

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of

• of an unsaturated fourteen- or sixteen-membered macrolactone decorated by an ʟ-cysteine-derived 2-oxo-1,3-thiazolidin-4-yl substitutent, and the presence of five stereogenic centers forming a 1,2,4,6,9-stereopentade (Figure 1). In latrunculins A (1) and B (2) three of them are embedded in a lactol

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• configurations of all its stereogenic centers match those of swainsonine. Furthermore, DIM is a micromolar GMII inhibitor, which is easily accessible on a large scale from ᴅ-mannose by well-established methods [15][29]. In general, improvements of physicochemical and inhibitory properties of monocyclic

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• compound 24 was rationalized by an isomerization of the double bond prior to the cyclization step. Isolated from the Ecuadorian liverwort Anastrophyllum auritum in 1994, ent-fusicoauritone (28) is a diterpene presenting a fusicoccan skeleton with a β-hydroxyketone on the A-ring and 5 stereogenic centers

• backbone with 8 fused rings, a unique [7-8] bicyclic motif, an oxa-bridge over the cyclooctane ring, and the presence of 12 stereogenic centers [36]. The strategy proposed by the authors was to carry out a RCM reaction to elaborate the cyclooctene ring from functionalized intermediate 66, prepared as a

• -8-6-5] tetracyclic all-carbon system with 10 stereogenic centers (Scheme 15). This natural product was isolated from two Gentianella plant species, namely G. nitida and G. alborosea used in Peruvian traditional medicine. The first report of its synthesis was given in 2014 by Hog and co-workers [46

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• a stereocontrolled manner. Stereogenic centers on the ethylenedithiol tethering group can give modest levels of stereoinduction (Scheme 11b), despite the relatively remote relationship between the stereogenic centers [60][61]. Guaragna, Palumbo, D’Alonzo and co-workers have very productively used

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

• and final dehydration by Burgess reagent provided the total syntheses of magninoids A (104) and C (103, Scheme 8). Divergent total synthesis of crinipellins (Xie and Ding 2022) [53]: Crinipellins are highly congested tetraquinane natural products comprising 6–10 stereogenic centers, three of which are

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• aminobisabolene sesquiterpenoid halichonic acid ((+)-1) from the sponge Halichondra sp. (Figure 1) [4]. This amino acid natural product features a rigid 3-azabicyclo[3.3.1]nonane ring system containing four stereogenic centers within the piperidine ring. In 2021, the same group re-isolated (+)-1 from the sponge

• Axinyssa sp. along with the structurally related compound halichonic acid B ((+)-2) [5]. Structurally, (+)-2 is a pipecolic acid derivative containing a cyclohexenyl ring as a substituent group. This compound also features four stereogenic centers (three of which are located within the piperidine ring) and

• the resulting tertiary carbocation to occupy equatorial positions (14), establishing the observed trans-relationship between these groups while simultaneously setting two new stereogenic centers. As before, one can envision several different fates for the tertiary carbocation present in 14. Although

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

• tetracyclic carbon skeleton yet-to-be found in Pseudopterogorgia elisabethae species, although related cyclohexane-angularly-fused triquinane systems have been found in waihoensene (3), conidiogenone (4), lycopodium alkaloids magellamine (5) and lycojaponicumin C (6) (Figure 1). Its seven stereogenic centers

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• stereogenic centers at C2, C6, C10, and C14 introduced during the two cyclization steps, FC-type diterpene synthases (DTSs) could be divided into 16 subtypes [20]. Furthermore, considering the modes of potential carbocation rearrangement and final carbocation quenching, there might be more FC-type DTSs in

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• -tricarbonyl compound 108 to set two stereogenic centers and correct one via an intramolecular aldol addition (108 → 109; Scheme 18) [34]. The vic-tricarbonyl compound 108 was synthesized via DMDO oxidation from α-diazo-β-ketoester 107, which was easily accessible from 5-methoxy-4H-chromen-4-one (106). The