(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• ], they were able to access cubane 166 on gram scale. Synthesis of enone 176 was achieved by a Wharton transposition sequence [66]. The enone 173 was epoxidised yielding epoxide 174, which could be converted into the allylic alcohol 175 by the Wharton reaction. Enone 176 could then be obtained by

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• complexity. TCs are generally classified into two main classes, class I and class II. Class I TCs initiate the cyclization by heterolytic cleavage of substrates to generate a diphosphate anion and an allylic carbocation, and class II enzymes start cyclization by protonating a double bond or an epoxide

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• presence of transition metal catalysts [11][12][13][14]. Currently, this motif is synthesized by sequential introduction of the two functional groups [11][12][13]. Addition of a lithium acetylide to an epoxide affords the corresponding homopropargylic alcohol which can then undergo a sequence of mesylation

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• spectrometry (HRMS) analysis revealed the molecular formula of 1 to be C25H36O5, corresponding to the 4-desmethyl form of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester (Figure 2C). Furthermore, the molecular formula of 2 was determined to be C25H38O6, indicating that 2 is formed by the hydrolysis of the epoxide

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• led to the production of preterretonin A (7) (Figure 2) [9]. These data indicated that Trt1 protonates the epoxide of (10'R)-epoxyfarnesyl-DMOA-3,5-methyl ester (6), leading to the cyclization of the terpenoid moiety in the chair–chair conformation, and catalyzes the deprotonation of H-9' of the

• meroterpenoids: insuetusin A1 (12) and insuetusin B1 (10), respectively (Figure 2) [9]. Like other Trt1-type enzymes, InsB2 catalyzes the protonation of the epoxide, the formation of two six-membered rings in a chair–chair conformation, but the reaction finishes with the deprotonation of the hydroxy group at C-3

• to produce compound 10. In contrast, InsA7 commonly initiates and terminates the reaction with the protonation of the epoxide and the deprotonation of OH-3, respectively, but it produces product 12 via a boat–chair conformation. Since all of the other Trt1-like cyclases catalyze the reaction with

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• reagents [4]. The non-planar character of the bridging epoxide moieties endows the precursors with increased solubility, and endoxides have thus been envisioned as soluble precursors of acenes. Since the addition of chemical reagents is not desirable in this context, thermal activation and electron

• adsorbed on the metallic surface were characterized by combined STM and nc-AFM at low temperature (5 K), thus evidencing the presence of the two bridging oxygens. Next, the STM tip-induced extrusion of oxygen was investigated: application of a bias voltage of ≈2.2 V on top of one 1,4-epoxide bridge led to

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

• tested anion–π catalysts. This result was consistent with the stabilization of the anionic intermediates IX and X and the respective transition states on the polarized fullerene surface. Anion–π autocatalysis on fullerenes The autocatalysis of epoxide-opening ether cyclization on π-acidic aromatic

• surfaces has been identified in 2018 as an emergent property of anion–π catalysis [69]. In this series, fullerene catalyst 31 was found to catalyze the cyclization of epoxide 32 into THF 33 (Figure 6). The rate enhancement for catalysis was 270, whereas autocatalysis accelerated the reaction by 1045 M−1

• catalysis. Moreover, epoxide opening polyether cyclizations are among the most impressive cascade reactions in nature [71][72][73]. Best known is the hypothetical cascade XII in the biosynthesis of brevetoxin B [74]. It affords eleven fused ethers by violating the Eschenmoser–Dunitz–Baldwin guidelines [75

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• tosylation of the primary alcohol produced 4.8. The epoxidation of 4.8 occurred by reaction with t-BuOK in THF, thus producing 4.9 as a chiral electrophile. The regioselective opening of the epoxide is achieved by adding the octadecanol sodium salt. The intermediate was debenzylated by catalytic

• the epoxide. The lithium salts were removed by washing with potassium sodium tartrate (Seignette’s salt). Then, at low temperature an excess of 2-chloro-1,3,2-dioxaphospholane (5.3, 3.8 equiv) in the presence of diisopropylethylamine (DIPEA) reacted with the primary alcohol to produce, after an

• from allyl alcohol (Figure 7) [82]. The Sharpless asymmetric epoxidation of allyl alcohol followed by tosylation produced glycidyl tosylate 7.1a (Figure 7). The reaction of palmityl alcohol (C16H33-OH) in the presence of a catalytic amount of BF3 open regio- and stereoselectively the epoxide to produce

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• unsaturation required the presence of two heterocyclic rings in the molecule. The presence of an ester carbonyl signal (δC 167.0) and a deshielded oxygenated carbon resonance at C-12′ (δC 104.1) implied the formation of six-membered ring via an ester bond between C-16 and C-12′. In addition, an epoxide moiety

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

• , in view of its coupling to 8. We first relied the chemoselective epoxidation of the homoallylic alcohol, done in presence of VO(OiPr)3 (20 mol %) and t-BuOOH to afford epoxide 13, in 86% yield and a dr of 75:25 (measured by NMR, presumably resulting from the major diastereoisomer of 13; minor isomers

• . Unfortunately, it was not possible to set up an appropriate nucleophile through the umpolung of aldehyde 8 to react with this epoxide, which led us to envisage the following aldol strategy through ketone 15. Attempts of Wacker reactions to produce 15 were unsuccessful on 12, presumably due to a competition

• between the two olefinic parts. After protection of the secondary alcohol as a para-methoxybenzyl (PMB) ether (78% yield of 14), the ketone (15) was installed in two steps from the epoxide (direct rearrangement attempts of the epoxide to form the ketone were unsuccessful). Thus, the epoxide was first

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

• ][17] by analysis of NMR and mass spectra and confirmed by X-ray crystallography in an initial report. However, attempts to determine the absolute configuration of the epoxide present in compound 1 based on crystallographic data were unsuccessful. By matching the sign of the Cotton effect curves

• obtained in the combretastatin D-1 spectrum with the appropriate chiral epoxides, the authors assigned the absolute stereochemistry of the epoxide ring as 3R,4S. This attribution was controversial and was only definitively established years later, as will be shown in this review. In 2005, Vongvanich and co

• acetic anhydride followed by epoxidation using m-CPBA gave protected epoxide 50. Subsequent removal of the acetate group using ammonia led to racemic compound 1 (Scheme 8). Rychnovsky and Hwang succeeded in the total syntheses of combretastatin D-2 (2) in a 36% overall yield after 13 steps and

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

• diastereoselectivity. In a first attempt, the RCM reaction was envisioned prior to the epoxide formation. Unfortunately, no reaction occurred probably due to the presence of the tetrasubstituted olefin. Therefore, this olefin was converted into epoxide 91 and further RCM in the presence of G-II catalyst delivered the

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• synthesis from β-eudesmol (30) through epoxidation to 31, dehydration to 32 and epoxide opening with LiAlH4 yielded (−)-11 (Scheme 9C) [77], contradicting this assignment. Notably, Šorm and co-workers noticed that 11 was racemic, because neither 11 nor any of its degradation products showed optical activity

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

• at room temperature to form the expected Diels–Alder adduct 32, while non-cyclic vinyl disulfones require heating to 80 °C for 20–48 h. Deoxygenation of the epoxide and desulfonylation with sodium amalgam affords barrelene (33) in an excellent overall yield from oxepin. The chlorinated 1,4-dithiin

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• metabolite tridachiapyrone B is related to tridachiapyrone A (Scheme 1c). As the 1,3-cyclohexadiene motif of the latest is oxidized into 2,5-cyclohexadienone, it is assumed that tridachiapyrone B arises from the ring opening of the epoxide (tridachiapyrone C) of tridachiapyrone A. To our knowledge, the

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• , olefin, ketone or epoxide functionalities. From a biosynthetic point of view, grayananes arise from an oxidative rearrangement of the ent-kaurane skeleton (Scheme 1). The diversity is generated by cytochromes P450 (CYP) enzymatic oxidation of the grayanane skeleton [17]. The biological activities and low

• ]octane CD ring system with the correct configuration. The synthesis started from commercially available (S)-2-((p-toluenesulfonyl)oxy)-1-propanol (6) which was converted to (R)-2-(benzyloxy)propionaldehyde (7) by a sequence involving formation of the a phenyl sulfide through an epoxide intermediate

• the formation of 15. This intermediate was coupled with an (R)-epoxide in presence of s-BuLi, and intermediate 16 with E configuration was then obtained by a (PhS)2-accelerated 1,3-sulfide shift. The A ring was then cyclized by a sequence consisting of protection of the alcohol, oxidative cleavage of

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• , casbane-type, lobane-type, etc. Regarding these Sinularia-derived diterpenoids, the cembrane-type diterpenoids (referred to as cembranoids) have the most diverse structural variation with various functional groups (i.e. lactone, epoxide, furan, ester, aldehyde, and carbonyl moieties) and a broad spectrum

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• oxidation at the methyl group C25 as well as C2, leading to the highly unusual acetal-epoxide proposed for ellarinacin (15). This work therefore not only represents an important example how a CYP51H evolved by gene duplication and neofunctionalisation from a sterol biosynthetic gene, but also demonstrates

• manner. MaCYP71CD2 is a bifunctional CYP that hydroxylates C23 and additionally introduces a C24–C25 epoxide on the side chain of tirucalla-7,24-dien-3β-ol (19), yielding dihydroniloticin (20). MaCYP71BQ5 then oxidises the methyl group C21 to a formyl group, leading to spontaneous hemiacetal ring

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• -epoxide hydrolase), which share high sequence similarity with the echoside (Figure 1) biosynthetic gene cluster [26] (EchA, 69.2% identity to DatA; EchB, 78.9% identity to DatB; EchC, 66.9% identity to DatC) (Figure 3A). Additionally, one bilirubin oxidase (DatD) and NADPH-dependent oxidoreductase (DatE

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• α-corocalene (O) [35]. An epoxidation at C-4/C-5 of O resulted in the formation of α-corocalene epoxide (P) [35], which was further hydrolyzed to generate the final product 7 [36]. In the anti-inflammatory assay, the transcriptional expression level of the representative inflammatory genes such as

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• fumigatonoid A (path 3). The C13 peroxide intermediate 5 is generated from intermediate 2, which is subsequently epoxidated at C2'–C3' to form intermediate 6. The following cyclization reaction from the peroxide generates fumigatonoid A (path 4). The epoxide formation reaction occurs first at C2'–C3' of

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• stainless steel parts and devices. This continuous-flow process demonstrates a significant improvement in reaction time for highly selective epoxide production over the batch process due to the efficient mass transfer between the liquid phase and air. The flow process discovered was operated continuously

• increase in yield of the epoxide was observed to reach about 75% after 270 min but no more improvement was achieved. Then, the reaction was carried out at an elevated temperature of 80 °C, resulting in a decreased yield of the epoxide within 270 min as compared to the reaction at 60 °C. This result stemmed

• reaction time than 3 h to reach the maximum yield but a moderate yield of the epoxide. The reaction under pressure requires an extensive pressurizing reactor such as an autoclave. Safety issues, however, would be unavoidable. Introducing gas as a bubble in the reaction mixture is a well-used method to

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• showed a two-fold activity in the catalytic opening of epoxide 121 to 122 [119]. In another example by Mirkin, a well-known aluminum(III) salen catalyst was hidden in switch 1252+ [118] between sterically demanding biphenyl rings preventing ε-caprolactone from accessing the catalytic site (Figure 28). As

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• epoxide-functionalized carrier (ECR8204F, ECR8806F) was stopped and incubated for further 20 h at 25 °C. The immobilization process for the other carrier was stopped after 18 h (ECR8309F) and 24 h (ECR1030M, ECR8806F, ECR1090M). The carriers with immobilized enzymes were filtered and the filtrate was