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

• hydroxy group could be responsible for this reversal in selectivity. Dai’s asymmetric synthesis of (−)-illisimonin A In 2025, Dai and co-workers accomplished an asymmetric total synthesis of (−)-illisimonin A in 16 steps from (S)-carvone (67) using a pattern-recognition strategy and five sequential olefin

• configuration. Kalesse and co-workers accomplished the first asymmetric total synthesis of (−)-illisimonin A based on strategies involving spiro substructure assembly and rearrangement. Consideration of the biosynthetic pathway of illisimonin A inspired Yang and co-workers to develop a bioinspired synthetic

• route. Employing a pattern-recognition strategy, Dai and co-workers achieved the second asymmetric total synthesis of (−)-illisimonin A in 16 steps. Lu and co-workers realized the shortest and gram-scale total synthesis of racemic illisimonin A in 15 steps by leveraging a higher-order cycloaddition

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

• core, successfully completing the first asymmetric total synthesis of ryanodol (4) in 41 steps. To elucidate the role of the C15 hemiacetal hydroxy group in ryanodine (1)-type diterpenoid natural products in binding to ryanodine receptors, the authors initially proposed reducing the lactone moiety in

• ). Furthermore, from intermediate 57, the introduction of an isopropyl group at C2 and subsequent deprotection furnished cinnzeylanol (6). Reisman’s total synthesis of (+)-ryanodine (1), (+)-20-deoxyspiganthine (2), and (+)-ryanodol (4) In 2016, the Reisman group at Caltech reported an asymmetric total synthesis

• , epoxidation of the C1–C2 double bond, and Li/NH3-promoted reductive cyclization to construct the core E ring, completing the asymmetric total synthesis of (+)-ryanodol (4). The 800-fold greater binding affinity of (+)-ryanodine (1) for cardiac ryanodine receptors (RyRs) compared to its hydrolysis product

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• . Asymmetric total synthesis of lycoplatyrine A. Photoreaction of pyrrolidine-derived phenyl keto amide. Photoredox reactions of naphthoquinones. Synthetic study toward γ-rubromycin. Substituent-dependent conformational preferences. Total synthesis of preussomerins EG1, EG2, and EG3. Acknowledgements This

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

• shortage of natural product sources. Nevertheless, the asymmetric total synthesis of terpenoid and alkaloid natural products presents significant challenges due to their complex and diverse ring systems and the presence of multiple stereocenters, including all-carbon quaternary stereocenters. Consequently

• , the development of novel methods and strategies to achieve efficient asymmetric total synthesis of complex terpenoid and alkaloid natural products has drawn considerable attention from synthetic chemists. Over the past decades, the development of desymmetric enantioselective reduction strategy of

• co-workers accomplished the first asymmetric total synthesis of (+)-aplysiasecosterol A (6) by employing a desymmetric enantioselective reduction strategy of 1,3-cyclopentanedione derivative as the key transformation [14]. Their synthesis features a highly efficient desymmetric enantioselective

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

• powerful routes to the asymmetric total synthesis of these bioactive molecules. The precursors of the key bioinspired transformations 36, 38 and 40 were efficiently synthesized from simple fragments aryl aldehyde 42 or 43, phenylboronic acid 44 and chiral auxiliary-containing building block 45, through

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

• synthesis of tricyclic-PGDM methyl ester in 9 steps and 8% overall yield. Keywords: asymmetric total synthesis; oxidative radical cyclization; tricyclic prostaglandin D2 metabolite methyl ester; Introduction Prostaglandins (PGs), a family of hormone-like lipid compounds, are ubiquitous natural products

• ring system with the appropriate functional groups in place for attaching the remaining groups is a highly important task for the asymmetric total synthesis of PGs and analogues [10][11][12][13]. The groups of Aggarwal [14], Hayashi [15], and Zhang [16] have reported bond-disconnection strategies for

• stereoselectively access the syn-anti-cyclopentanol ring system with three vicinal stereogenic centers at C11, C12, and C8 via the oxidative radical cyclization that led to the asymmetric total synthesis of compound 4. Results and Discussion First generation asymmetric total synthesis of tricyclic-PGDM methyl ester

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

• , 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

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

• successfully treated by artemisinin combination therapy (ACT). Artemisinin can be isolated from the Artemisia annua (sweet wormwood) plant. This sesquiterpene lactone bearing a peroxide is a prodrug of the biologically active dihydroartemisinin. In 2012, Zhu and Cook developed a gram-scale asymmetric total

• synthesis of (+)-artemisinin (Scheme 55) [102]. Using the commercially available and cheap cyclohexenone 1 as starting material, they have demonstrated an economic synthesis plan in only five steps. In the first step, the Cu-catalyzed conjugate addition of Me2Zn is followed by alkylation with 1-bromobut-2

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

• Cav3.1 calcium channel. From a chemical point of view, hypoestin A (177) presents a complex structure: it is composed of a [5-8-5-3] tetracyclic core skeleton, with five stereogenic centers, whose four of them are contiguous. Before their work, no asymmetric total synthesis of hypoestin A (177) has been

• reported. During this study, they also looked into the asymmetric total synthesis of albolic acid (178) and ceroplastol II (179). Only one paper reported their total synthesis, using a reductive coupling of aldehydes for the synthesis of the eight-membered ring with an excellent yield of 96% [82]. However

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• tertiary amine-thiourea catalyst (cat. 82). This cascade reaction afforded aza-Michael adducts in 77–92% yields with high ee (up to 90%) (Table 19) [55]. Du et al. developed an enantioselective catalytic tandem aminolysis/aza-Michael addition for the asymmetric total synthesis of two natural Apocynaceae

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• efficiently utilized for the synthesis of highly strained tricyclo[5.2.1.01,6]decene intermediate 214 containing a cyclobutane ring (Scheme 64). Compound 213 is an important precursor for the asymmetric total synthesis of solanoeclepin A. The formation of β-hydroxyketone 213 was achieved by Hg(TFA)2-mediated

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• Grignard reagents to α,β-unsaturated thioesters and their application in the asymmetric total synthesis of (–)-lardolure. Improved Cu ECA of Grignard reagents to α,β-unsaturated thioesters, and their application in the asymmetric total synthesis of (−)-mintlactone. Catalytic enantioselective synthesis of

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• isolated from fungi of the genus Acremonium. Here, we present the asymmetric total synthesis of acremine F which hinges on a modestly enantioselective dihydroxylation and a subsequent kinetic resolution via a highly selective asymmetric reduction. Chemoselective oxidation of acremine F gave access to

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• the reported procedure finalized the synthesis of triptolide. Overall, the first asymmetric total synthesis of (−)-triptonide (19 steps, 0.06% yield) and formal synthesis of triptolide were realized from ʟ-dehydroabietic acid (26). Although the overall yield of the synthesis is very low, the authors

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• de values of more than 95% in both cases [65]. Kibayashi prepared a set of optically active acylnitroso arylmenthol derivatives 142 (Scheme 27) that were subsequently reacted with 1,3-cyclohexadiene (120) to give the hetero-Diels–Alder products 143, serving as intermediates for an asymmetric total

• synthesis of (−)-epibatidine [5][124]. The stereoselectivity of the reaction was affected by the substituent on the menthol group. The introduction of a phenyl and a 4-methoxyphenyl substituent gave the products with de values of >85%, but this could be improved to up to 91% for the 2-napthyl, 4-bromophenyl

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• oxidative coupling – initially between 3-methoxycatechol (100) and tert-butyl 1-oxoindan-2-carboxylate (101) using an adamantane derivative of cupreidine CPD-102 to give the corresponding adduct 103 in 84% yield and 81% ee (Scheme 24a) [69]. An attempt to develop this methodology towards an asymmetric total

• synthesis of buphanidrine (104) and powelline (105) led to the bespoke development of another cupreidine catalyst CPN-107. Unfortunately, although the resulting adduct 108 (after alkylation of the catechol) was produced in a 70% enantiomeric excess (Scheme 24b), subsequent steps that had worked with the

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• unprecedented heterocyclic core (2-nitro-4-farnesylpyrrole) with closely related levels of oxidative functionalization of the farnesyl side chain. In 2012 Stark et al. employed a biomimetic strategy to deliver the first asymmetric total synthesis of heronapyrrole C, confirming its constitution and establishing

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• steps in a 25% overall yield starting from N-Boc-D-alanine. The spectroscopic data and optical rotation are in agreement with the literature [6]. Conclusion In conclusion, we have achieved the asymmetric total synthesis of (−)- epimyrtine in six steps and with a good overall yield. We have demonstrated

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• retrosynthetic analysis. Attempted proline catalyzed aldol reaction. Second retrosynthetic analysis. Asymmetric total synthesis of smyrindiol (1). Supporting Information Supporting Information File 77: Experimental procedures and characterization of compounds. Supporting Information File 78: NMR-spectra and

A new phenylethyl alkyl amide from the Ambrostoma quadriimpressum Motschulsky

• Guolei Zhao,
• Chao Yang,
• Bing Li and
• Wujiong Xia

Beilstein J. Org. Chem. 2011, 7, 1342–1346, doi:10.3762/bjoc.7.158

• -phenethyloctadecanamide (1), was isolated from the beetle Ambrostoma quadriimpressum Motschulsky. The structure of the amide was determined by NMR and MS. The absolute configuration of compound 1 was confirmed by an asymmetric total synthesis, which was started from L-glutamic acid. The construction of the aliphatic

• positive optical rotation ([α]20D +38.5 (c 0.13, CHCl3)). To confirm the absolute configuration at C(10), an asymmetric total synthesis was performed. Synthesis of (10R)-10-hydroxy-N-phenethyloctadecanamide (1) The retrosynthetic analysis of compound 1 is outlined in Scheme 2. The target molecule is

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• position of hydroxy substituents is critical for selectivity. In the seminal work by Lebreton and coworkers [73], the first asymmetric total synthesis of (+)-adenophorine was achieved in 14 steps (3.5% overall yield, Scheme 23), starting from the Garner’s aldehyde 69. RCM is essential for construction of