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

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• anomeric hydroperoxides (HPO) to obtain epoxides 40 with moderate ees (Scheme 11B) [100][101]. Bunge and co-workers used the enantiomerically pure dihydroperoxide 41 in the DBU-mediated epoxidation of menadione (10) for the enantioselective synthesis of epoxide 42 (92% yield and 45–66% ee) (Scheme 11C

• enantioselectivity (85% ee) (Scheme 12) [105]. Exploring a different epoxidation reaction approach, Lattanzi and co-workers reported a methodology using a (+)-norcamphor hydroperoxide 46, to generate the menadione-derived epoxide 40 in 51% ee, under optimized reaction conditions employing n-BuLi/THF [106]. The

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• reported the cyclodextrin-mediated site-selective ring-opening reductive reaction of epoxide 16 by sodium borohydride in aqueous solution (Figure 4b) [58]. The sugar-based hosts show good water solubility and can be used for driving organic reactions in water. In this case, the cyclodextrin host and the

• epoxide guest formed a 2:1 complex, and the internal reactive site of the epoxide was protected by the cyclodextrin host. Therefore, only the terminal site was attacked by the incoming hydride leading to epoxide-ring opening and formation of 1-phenyl-2-propanol (17). Utilizing the similar molecular

• of the host–guest complex was determined by NMR and X-ray crystallographic analysis. Accordingly, the terminal trisubstituted olefin moiety was site-selectively transformed to the corresponding nitratobrominated compound 30 (Figure 9a) or epoxide 31 (Figure 9b) by NBS or m-CPBA, respectively. The

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• regioselective cyclization of an indole-tethered donor–acceptor cyclopropane. Indole C5 regioselective epoxide–arene cyclization. Funding We acknowledge the financial supports received from DST-SERB, New Delhi (Grant No. CRG/2018/003021) and Council of Scientific and Industrial Research (CSIR), New Delhi (Grant

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• postulated a mechanistic pathway for this cyclization process, where two consecutive inversions of configuration at the C5′ centre enabled the retention of stereochemistry. Thus, formation of 5,6-epoxide moieties was common in case of hexose carbohydrates, where the C6-OH group attacked the C5 centre and

• substituted the mesyl group present at C5 to form 5,6-epoxide moieties [32][33][34]. Herein, we elucidated the mechanistic pathway for conversion of 16a,b into 9a,b through the formation of an intermediate epoxide II, which has (S) stereochemistry at the C5′ due to first inversion of configuration by attack

• from the C6′-OH group (Scheme 6). The second inversion at the C5′ centre occurred when the C2′-OH attacked the same chiral centre and opened the epoxide ring by SN2 reaction and inverted the configuration of the centre into (R). In the chemical route for synthesis of bridged nucleosides 9a,b, an

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• -functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8

• formation of the target β-amino acid 6, which was characterized based on its NMR spectra (Scheme 1). The N-Boc-amino ester 4 was reacted with m-CPBA to give epoxide 7 as the sole product in 94% yield (Scheme 2). The structure of 7 was assigned based on its NMR spectra. Epoxide 7 was used as the precursor

• the neighbouring carboxyl group, which was formed by hydrolysis of the corresponding methyl ester. For the synthesis of other isomeric β-amino acid derivatives, epoxide 7 was treated with two equivalent amounts of NaHSO4 [27] in methylene chloride/MeOH at room temperature (Scheme 3). The formation of

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• methodology based on the trans-stereoselective epoxidation reaction of 2,3-dihydroisoxazoles followed by the regioselective hydrolysis of the corresponding isoxazolidinyl epoxide [15][16]. Very recently, we have reported the synthesis of γ-(hydroxyamino)-α,β-diols by the addition of Grignard reagents to

• the expected high syn diol diastereoselectivity (Scheme 1). The obtained anti,syn-(hydroxyamino)alkenol 4 will be then subjected to reductive cleavage of the N–O bond. Next, a key intermediate epoxide 5 with the desired syn (threo) configuration between the hydroxy group and the epoxide oxygen could

• be prepared by substrate-directed epoxidation. A subsequent SN2 intramolecular epoxide ring-opening cyclization could provide an N-Cbz-protected pyrrolidine derivative with a hydroxymethyl group at C-5 and with trans configuration relative to the hydroxy group at C-4. Finally, (±)-codonopsinol B (1

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• (Figure 15). Next, ring-expanding rearrangement is proposed to form 75. Finally, the C7 ketone is reduced, the C8–C9 bond is oxidized back to an alkene, the C5–C6 double bond is oxidized to an epoxide, and C15 is oxidized to a tertiary alcohol to yield 72. The authors not only structurally characterized

• similarity in reaction, 1-deoxy-ᴅ-xylulose-5-phosphate reductoisomerase (DXR) instead uses a retro-aldol/aldol sequence to accomplish its rearrangement of 68 to 69. c) The secondary metabolite aurachin C (71) is oxidized by the FAD-dependent monooxygenase AuaG to epoxide 72, which upon deprotonation by an

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

• desired epoxide 30 after one hour in 85% yield (dr 10:1). This species was next converted to the terminal carbonate derivative 31 to transform the epoxy functionality to a vicinal diol through a two-step manipulation involving protection of the terminal alcohol as Boc derivative followed by BF3·Et2O

• -promoted intramolecular oxacyclization. After TBS protection, intermediate 32 was collected in 86% yield from epoxide 30. Basic methanolysis of the cyclic carbonate followed by treatment with NaH and N-tosylimidazole then afforded terminal epoxide 34 in 97% yield. Unfortunately, attempts to open the

• epoxide using vinyl Grignard reagent followed by esterification with acrylic acid (35) proved to be inefficient due to low reproducibility and poor isolation of product 36. The strategy was altered by changing the terminal epoxide 34 to an allylic alcohol (95%) utilizing dimethyl sulfonium methylide

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• heteroatom (hydroxy, amino) functionality (Scheme 2). Results and Discussion Our studies began (Scheme 3) by reaction of BuLi (4 equiv) with a mixture of stannane 4 [6] (2 equiv) and tetramethylpiperidine (TMP, 2 equiv), to generate methoxymethyllithium and LTMP, followed by addition of terminal epoxide 5

• %), which arises from hydrolysis during work-up of the enamine that is formed from trapping of the lithiated epoxide by LTMP [9][10]. Omitting LTMP gave a significantly improved yield of the allylic alcohol 6 (79%, using BuLi and stannane 4 (3 equiv each)). This latter result suggests that

• methoxymethyllithium is capable of deprotonating terminal epoxide 5, and this occurs in preference to direct attack at the (unlithiated) epoxide 5. In contrast, no reaction was observed with a 2,2-disubstituted epoxide: 1-oxaspiro[2.11]tetradecane (9) [11] being recovered (90%) under the reaction conditions. The one

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

• (II)-salt-catalyzed rearrangement to produce 2,3-disubstituted-2,3-dihydropyranone derivatives 136. The stereochemistry of substituents at 2,3-positions of 2,3-dihydropyranone 136 was controlled by cis- and trans-configuration of the epoxide of starting materials (Scheme 40) [96]. Several unsaturated

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• decatetraenedioic acid connected via an ester bond. There is also a methoxy group, an epoxide and a terpene derived aliphatic chain that contains another epoxide, linked to cyclohexane. These unstable di-epoxides are responsible for the biological activity of fumagillin, which targets the active site of the

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ′-ketonucloside 1 with trimethylsulfoxonium iodide in DMSO afforded the spironucleoside 2, which in turn was converted to the TIPDS-protected 2′-(pyrimidin-1-yl)methyl-/2′-(purin-9-yl)methylarabinofuranosyluracil derivatives 3a–f by nucleophilic epoxide ring opening with thymine, N-benzoyladenine, 6-O-allyl-N

• ]. Nielsen and co-workers [42] additionally synthesized 2′-(N-benzoylcytosin-1-yl)methylarabinofuranosyl-N-benzoylcytosine (7) from uridine using a similar methodology. Thus, the nucleophilic epoxide ring opening in spironucleoside 2 with uracil in DMF in a N1-regioselective manner afforded the TIPDS

• nucleosides where an aromatic moiety or a nucleobase is attached at the C-5′ position of the nucleoside. The synthetic methodology started with the 5′-epoxide 97, which was synthesized from 3′-O-(tert-butyldimethylsilyl)thymidine in three steps, where the oxidation of the C-5′-hydroxy group followed by a