Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• preparation of BS 4 and 5 with a 2,3-epoxide moiety (Scheme 1). To date, only the corresponding 6-ketones were found in natural sources (2,3-diepisecasterone [10] with an α-oriented epoxide 4 and two BS with a β-oriented epoxide 5: secasterone [10][17] and 24-episecasterone [18]). The synthesis of both

• [19]. The 7-membered B ring in 21 had no influence on the stereochemical outcome of the reaction with MCPBA which resulted in the formation of the α-epoxide 22. The same was true for the electrophilic addition of Br+ to the olefinic unit of 21. It produced the trans-diaxial bromohydrine 23 that was

• transformed, on treatment with KOH, into the epoxide 24. The structures of isomeric epoxides 22 and 24 were confirmed by their NOESY spectra as shown in Scheme 4. The obvious NOE correlation between H-3 and H-5 in 24 suggested the spatial vicinity of these two protons, thus the epoxide ring was β-oriented. On

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• have previously reported a concise method for synthesising compounds that contain three vicinal C–F bonds [34]; their method commences with an epoxy alcohol, which undergoes three successive nucleophilic substitutions with fluoride (i.e., deoxyfluorination of the alcohol, epoxide ring opening with

• Et3N·3HF according to O’Hagan’s method [34] (Scheme 3). This did effect epoxide-opening to some extent, but the reaction was rather unsatisfactory because it was low-yielding and non-regioselective, which made full characterisation of the product mixture (32/33) impossible. Nevertheless, an analytical

• it was found that the inclusion of the additive TMS-morpholine [36][37] was also required to ensure a high diastereoisomeric excess of 38a. The epoxide 38a was then ring-opened using Et3N·3HF to deliver the difluorodiol 39a as a mixture of regioisomers. This mixture subsequently converged during the

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• have recently been reviewed [34]. We have previously reported syntheses of heliannuols C, D, and E via intramolecular epoxide opening reactions [35][36], but this approach did not translate well to the synthesis of heliannuol A. One of our alternative strategies for the synthesis of heliannuol A was an

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• the C1–C20 seco acid via formation of the C9–C10 bond by an epoxide-opening reaction with an alkyne-derived alkenyl trialkylaluminate. A distinct strategy was also chosen by the Aggarwal group, which connected the linear C1–C11 fragment to the C12–C20 fragment employing their lithiation–borylation

• obtained according to literature procedures [133], thus setting the stereochemistry at C12. The five-step sequence from 20 to vinyl iodide 21 included a (poorly diastereoselective) epoxidation, epoxide opening with a propynyl anion and a hydrozirconation/iodination reaction to generate the vinyl iodide

• iodide 21. As illustrated in Scheme 2, the nine-step synthesis of the latter proceeded via key epoxide 30 and comprised a diastereoselective alkylation of diethyl (S)-malate according to Seebach and Wasmuth [136] to introduce the C12-methyl group (dr = 8:1). Although being longer than the 1st generation

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• by participation of the C2–OH group to release 1,3-dimethylimidazolidin-2-one (DMI), the anomeric leaving group. The epoxide is then opened by the nucleophile when added to the reaction mixture. In pathway C the α-DMC complex is displaced directly by the added nucleophile to liberate DMI, once again

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• allow in-depth exploration of the chemistry of this class of azasugar precursors. Some preliminary experiments were performed to assess the possibilities that these building blocks grant. Endperoxide 19 was epoxidized under standard conditions to provide the desired epoxide 25 and the anti-diol 26 as a

• by-product. Likely, diol 26 is formed by ring-opening of the epoxide by water present in the mCPBA and the reaction could be optimised by performing the reaction under anhydrous conditions. Attempts at cleaving the endoperoxide bond of 20 and 21 by catalytic hydrogenation resulted in rapid

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• that a large number of racemic and asymmetric syntheses of nebivolol and their intermediates have been described in the literature, however, the Sharpless asymmetric dihydroxylation has never been employed as the sole source of chirality for this purpose. Keywords: dihydroxylation; epoxide-ring

• opening; heterocycles; nebivolol; syn-epoxide; Findings Chiral chromans are prevalent components of a large number of natural products, natural product-like molecules and pharmaceutical drugs, possessing diverse biological activities [1]. In view of their wide spectrum of biological profiles, chiral

•  1, method 1). For this purpose, the necessary epoxide 6 could be obtained from the parent E-allylic alcohol through Sharpless asymmetric epoxidation (SAE) [11]. However, the corresponding parent Z-allylic alcohol appears to be not suitable to provide 7 under SAE conditions [20]. This has eliminated

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

•  1). The use of an integrated microflow system allowed the preparation of functionalized α-ketoamides by a three-component reaction between carbamoyllithium, methyl chloroformate and organolithium compounds bearing sensitive functional groups (i.e., NO2, COOR, epoxide, carbonyl) (Scheme 2). It should

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• ]) and from those of the epoxy-secosterol reported by Anta et al. (δC 65.5 and δC 58.1, respectively; [24]). The downfield shift, observed for these carbons in 1, results from the cleavage of the epoxide ring, and 13C values around δC 70–80 as observed for 1 are characteristic for hydroxylated carbons

• downfield resonances resulting from the lack of a carbon–carbon double bond. Instead, two characteristic 13C NMR shifts at δC 66.4 and 62.3, attributable to an epoxide moiety were present. 13C NMR data of 12 and the specific optical rotation were identical with those reported by Bowden et al. [37], ([α]D20

• and NOESY; all NMR spectral data in Supporting Information File 1, Figures S32–36 and Table S4) experiments and propose the absolute configuration of bisepoxide 12. Bisepoxide 12 has five stereogenic centers, found at the epoxide moieties between C-3 and C-4, and C-11 and C-12, as well as C-2 of the

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• synthesize dihydroxy substituted 1-indanones [91]. All reactions have been completed within 2–3 min at 0 °C in the presence of the catalyst Sn(IV)Cl4 (225) and gave products in excellent yields (90–98%). For example, 1-indanone derivative 224 has been obtained from the THP/MOM protected chalcone epoxide 223

• been proposed by Krawczyk et al. [93]. For example, optically active 1-indanone 230 was obtained from the cyclic enol phosphate 228 which next was reacted with a fructose-derived dioxirane 232 generated in situ from the ketone 231, to provide the epoxide 229 (Scheme 64). Then, the latter was hydrolyzed

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• . Results and Discussion In order to evaluate whether the CARR approach is suitable for epoxide detection, we azidated commercially available trans-stilbene oxide as representative model compound for 1 affording the vicinal azido alcohol, 2-azido-1,2-diphenylethanol (Supporting Information File 1, Figure S2

• product could be directly detected in the base-peak chromatogram (BPC) showing the characteristic fragmentation pattern of the CARR adducts (Supporting Information File 1, Figure S3) [15]. Additionally, the detection limit of the model epoxide was investigated in a complex environment. For this, defined

• amounts of trans-stilbene oxide were added to liquid Lysogeny Broth (LB) medium. The obtained methanolic Amberlite XAD-16 extracts were azidated, enriched and analyzed. Up to a final concentration of 5 µg/L (≈25 nmol/L) the epoxide could be detected (Supporting Information File 1, Figure S4). Following

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• attributed to their ability to form a hydrogen bond with the oxygen of epoxide. In 2015 Shirakawa and Maruoka demonstrated that ammonium salts L5 and L6 could serve as effective catalysts for isoquinolinium and pyridinium salt Mannich reactions (Scheme 7) [50]. Catalysts L5 and L6 were selected due to their

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• literature reports on bioactivities of brazilin, haematoxylin and their analogues and our fruitful experience [22][23][25][26] in intramolecular epoxide ring-opening chemistry including IFCEA cyclization, we became interested in the possibility of extending the IFCEA cyclization protocol to the

• that the [6,5]-ring system in brazilin and related natural products 1–4 remains cis-fused, its corresponding [6,6]-ring system in 5 can have cis or trans stereochemistry at the ring junction. In our previous work, we observed a cis relationship (both in concerted or/and stepwise-epoxide ring opening

• ) between the 4-aryl group and H atom at the C-3 position of 4-arylchroman-3-ols (thus giving rise to trans-4-arylchroman-3-ols) [22][23]. But it was not obvious how the planned IFCEA cyclization onto the pre-existing 6-membered ring, in case of stepwise-epoxide ring opening, would influence the product

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• theoretically upper limit of 50%. We discovered that 6, sold by Acros Organics as racemic compound, was actually enriched in the desired (R)-enantiomer (see Supporting Information File 1 for optical rotation values). Diene (R)-9 was obtained by reduction of the epoxide 6 with LiAlH4 to form alcohol (R)-7

• material. After copper-catalyzed opening of the epoxide with 6-heptenylmagnesium bromide obtained from 7-bromo-1-heptene (14) and Steglich esterification with 5-hexenoic acid (16), RCM using (Z)-selective Grubbs catalyst 12 was used to synthesize macrolide (R)-1 without any isomerization. Comparison of the

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• protection, afforded protected β-hydroxyenduracididine 40. Alternatively, formation of epoxide 45 provided access to diastereomer 41. Synthesis of β-hydroxyenduracididine by Oberthür et al.: In 2014, Oberthür et al. reported a second generation synthesis of β-hydroxyenduracididine using a more concise route

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• to an internal alkene to form an epoxide followed by a subsequent cyclization are not covered in this article as these are different in mechanism since the oxidation and cyclization are two distinct events and do not occur in the same step [3]. The attraction to generate up to four chiral centers

• ][68]. In 2013, the Fürstner group published a successful approach to amphidinolide F (24) applying an oxidative type C Mukaiyama cyclization reaction for the THF segment 22 (Scheme 7) [69][70]. Therefore, enantiomerically pure epoxide 20 was converted to 5-hydroxyalkene 21, the oxidative cyclization

• ][148][149][150][151]) using an elegant two-directional approach (Scheme 17). Thus, starting from a central THF diol 81 with a fully established carbon framework, which was derived from CS-symmetric bis-epoxide precursor 80, a double oxidative cyclization using Re(VII)-catalysis furnished the natural

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• 32 of each of these kinetic resolutions had the same absolute configuration. Combining these two complementary catalysts leads to a highly efficient parallel process wherein each catalyst enantioselectively hydrolyzes one enantiomer of the epoxide, ultimately forming diol (R)-32 in 92% yield with 89

• % ee [36]. An especially remarkable example of type III enantioconvergent catalysis utilizes a single enzymatic catalyst. Faber observed that Nocardia EH1 is capable of catalyzing the hydrolysis of racemic epoxide 33 to the corresponding diol (2R,3R)-34 in 79% chemical yield with 91% ee (Scheme 8) [37

• ]. The observed product arises from hydrolysis of each enantiomer of epoxide at the S-configured carbon atom. Isotopic labeling studies with 18OH2 not only confirmed this mechanistic hypothesis, but also facilitated kinetic studies to determine relative rate constants for each of the four reaction

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• for dimethyl carbonate production: Ionic liquid-based catalysts brought about a number of improvements for the synthesis of DMC. As mentioned above, the synthesis of DMC through CO2 insertion into an epoxide and the subsequent transesterification of the formed cyclic carbonate with methanol represent

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• oxocarbenium ion at C1 to which concomitant addition of a hydroxy group (present in the side chain at C3) will give the requisite pyranose ring skeleton. Intermediate B could be derived from the allyl alcohol C by using the Sharpless asymmetric epoxidation followed by regioselective epoxide ring opening with

• Sharpless asymmetric epoxidation (SAE) [16][17]. Thus, allyl alcohol 7 was subjected for SAE first using (+)-DET that afforded a diastereomeric mixture of epoxy alcohols 8 and 9 in the ratio of 88:12 (based on the 1H NMR analysis) in 85% yield. Similarly, use of (–)-DET in SAE afforded epoxide 8 and 9 in

• the ratio of 18:82 in 83% yield. With the understanding of SAE mnemonic, we assigned the absolute configuration in epoxide 8 as 7S,8S and in epoxide 9 as 7R,8R. Subsequently, major isomers of epoxy alcohols 8 and 9 were individually subjected to regioselective epoxide ring opening using trimethyl

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• -dione 87a to form epoxide 89a. The second step involves the Baeyer–Villiger oxidation of epoxide 89a to peroxide 90a followed by the rearrangement into intermediate 91a. The latter is hydrolyzed by H2O to form dicarboxylic acid 92a, which is cyclized under the acidic conditions to γ-lactone acid 88a

• formation of 108 takes place. Probably perester 109 is formed alongside of 108. After formation of 109, the reaction proceeds by two different routes A and B (second stage). The first route A leads to formation of epoxide 110, whereas the second route (B) proceeds through the Baeyer–Villiger reaction with

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• reaction. The ambruticins contain a second hydropyran ring that is established by epoxide opening (see chapter 1.1.3). A further enzyme with similar dehydratase–cyclase activity was recently discovered by Leadlay et al. in the biosynthesis of the polyether ionophore salinomycin (31, Scheme 5) [18]. SalBIII

• is a pyran-forming cyclase that was originally annotated as an epoxide hydrolase/cyclase. The putative biosynthetic precursor 29 was isolated from a gene knockout strain and used in an in vitro assay. The recombinant enzyme converted this compound into the cyclised salinomycin precursor 30. The

• building block [34][35][36]. 1.1.3 Epoxide opening: The nucleophilic opening of epoxides is probably the most abundant type of reaction leading to furans and pyrans. It, for example, plays an important role in the biosynthesis of ionophoric terrestrial and marine polyethers (see chapter 1.3). In this

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• , rac-12 and (E)-4. A comprehensive survey of the literature revealed three general synthesis routes to IPNs. In summary, Shepson et al. [17] reacted isoprene epoxide with concentrated nitric acid (Scheme 2, path A); Kames et al. outlined the O-nitration of simple alcohols using dinitrogen pentoxide [18

• ] (Scheme 2, path B); Cohen et al. reported the application of bismuth(III) nitrate for isoprene epoxide ring-opening/trapping with nitrate [19] (Scheme 2, path C). The 2010 report by Shepson et al. (path A) exploited chemistry originally described by Nichols et al. who, employing nitric acid as a

• convenient and cheap Brønsted acid, transformed a range of epoxides [20] into the corresponding nitrato alcohols. Shepson substituted ethylene oxide for commercially available isoprene epoxide and generated eight stereo- and structurally isomeric IPNs. Within this mixture 3° nitrate rac-7, 1° nitrate rac-8

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• Bamford–Stevens-like transformation, the reaction with the adjacent alkyne proved to be much faster to provide the bridged-polycyclic product 89. The conditions employed were sufficiently mild and chemoselective that the epoxide in cyclohexane 91 remained intact in the reaction to form 92. The use of

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• ]. The complete structure was elucidated via 2D NMR techniques, while NOESY correlations were used to study the configuration of the double bonds. However, the configuration at the epoxide bearing carbon atoms could not be resolved at that time. In further work, Kundim et al. [53] published three new

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• muraymycin core structure (Scheme 6) [78][99]. The key step of their route was a sulfur-ylide reaction with high substrate-controlled diastereoselectivity [100][101][102]. This epoxide-forming sulfur-ylide reaction had been established before by Sarabia et al. [103][104]. After some initial confusion

• regarding the stereochemical configuration of the epoxide product, it could be unambiguously proven that the transformation of uridine-5'-aldehyde 44 with sulfonium salt 45 under basic conditions furnished epoxide 46 with high diastereoselectivity (Scheme 6). Subsequent ring opening of this epoxide with

• analogues of muraymycins were also synthesised via suitable epoxide precursors by Ducho et al. [105]. Ducho's synthesis of epicapreomycidine (Scheme 7) started from the (R)-configured Boc-protected Garner aldehyde 51 [106], which was transformed into the N-benzylimine 52. The latter was then