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

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• commenced with the introduction of an azide at the 2α-position of the 1,6-anhydropyranose skeleton by nucleophilic cleavage of a 2β,3β-epoxide or the displacement of the C-2β triflate ester using mainly a combination of published procedures (Scheme 2). 2-Azido alcohols 11, 12 and 15 were obtained from 1,6

• ] of 14 followed by azidolysis [41] furnished 15. 2-Azido-3,4-epoxide 18 was prepared from readily available [42] 2,3-isopropylidene-D-mannosan (16) in five steps (Scheme 2). Tosylation of 16 [43], followed by hydrolysis of the benzylidene acetal [44] and oxirane ring closure [45] at C-4 delivered 1,6

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• modifications of natural products [23][24], such as N-Boc neomycin B under epoxide formation [25]. Elson et al. systematically investigated the mechanism of the reaction of menthol with p-nitrobenzoic acid using a Hendrickson or Mitsunobu reagent [26]. The Hendrickson reagent led to conversion of menthol into

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• is extremely high, and all together, over eighty derivatives have already been isolated, e.g., the epoxide-containing resibufogenin (38, Figure 7) was isolated from the Chinese toad skin extract drug Ch´an Su. It showed growth inhibition effects on human oral epidermoid carcinoma KB cells and murine

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• aldehyde 30 using PCC in dichloroethane. It was derivatized to its MOM derivative 31 using MOMCl and DIEPA in DCM. Darzens glycidic ester condensation of 31 with methyl 2-chloroacetate and sodium methoxide in methanol (Scheme 4) afforded the desired epoxide 32 [44]. The epoxide 32 was characterized by the

• signals corresponding to two protons of the epoxide at δ 4.18 and 3.54 [44]. Since the yield of 32 was low, we considered a Horner–Wadsworth–Emmons reaction of aldehyde 31 with triethyl phosphonoacetate as an alternative. Unfortunately, it was not successful, probably due to the interference of the

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

• , cupreine and cupreidine PTCs HCPN-65 and HCPD-67 were used in the epoxidation of the cis-α,β-unsaturated ketone 63 with sodium hypochlorite [53][54]. Interestingly, the use of these pseudoenantiomers did not lead to similar magnitudes of stereoselection in the opposite enantiomers of epoxide 64 that they

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• rearrangement [41] to afford an aldehyde that was converted to dimethylacetal 60. The following epoxidation proceeded with good stereoselectivity (α/β ≈ 11:1) and the regioselective opening of the epoxide moiety using lithium cyanide afforded a β-hydroxy nitrile in a trans-diaxial arrangement. Under basic

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• the protecting groups [35]. Compound 2 has also been synthesized starting from xylofuranoside by manipulating the protecting groups on the carbohydrate moiety [36]. De Clercq and co-workers [37] developed a protocol for the synthesis of 3’-fluororibofuranose in 10 steps, and it requires epoxide

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• precursors to gain insight into the used building blocks for the unusual polyketide core [26]. Compound 9 features a trisketal structure in addition to the spiro-epoxide at C-14, which is believed to be the active part of the molecule for interaction with DNA. This was supported by the isolation of

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• –carbon double bond in enamines to give the corresponding epoxides, however, in most cases they have not been isolated [36]. The hydroperoxide 2 reacts in the same way. Fission of the epoxide ring may be induced by the base itself producing 3. Attack of a second molecule of hydroperoxide 2 on the imine

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• epoxidation of 5 with tert-butylhydroperoxide (TBHP) in toluene gave 6 ([α]D +34.2° (c 1.3, CHCl3)) in 95% yield [9][22]. Then, the diol 7 was obtained in 85% yield from the reduction of epoxide 6 with LiAlH4 in THF at 0 °C. The diol 7 was easily purified by crystallization (85% yield, n-hexane at −50 °C up

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• compounds. The resulting cross metathesis products were hydrogenated in a tandem fashion employing the residual ruthenium from the metathesis step as the hydrogenation catalyst. Interestingly, the epoxide ring remained unreactive toward this hydrogenation method. The saturated compound resulting from the

• cross metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy alcohol and an amino alcohol in high yields. Keywords: cross metathesis; epoxide; ruthenium catalysts; tandem reactions; Introduction Catalytic carbon–carbon

• involving the cross metathesis of a commercially available epoxide-containing olefin with methyl acrylate and acrylonitrile and their subsequent transformations leading to multifunctional building blocks are reported. Results and Discussion Cross metathesis reactions involving electron-deficient olefins are

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• identified as a key building block. To this end, Fukuyama and co-workers [49] have used the RRM to generate the required building block 230. In this reaction, the required norbornene derivative 228 was prepared from epoxide 227 in two steps and later it was treated with the more reactive catalyst 6 in the

Robust bifunctional aluminium–salen catalysts for the preparation of cyclic carbonates from carbon dioxide and epoxides

• Yuri A. Rulev,
• Zalina Gugkaeva,
• Victor I. Maleev,
• Michael North and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2015, 11, 1614–1623, doi:10.3762/bjoc.11.176

• mixture and reused. Keywords: aluminium; carbon dioxide; cyclic carbonate; epoxide; salen; Introduction Carbon dioxide is a renewable and inexpensive carbon source, so great efforts have been directed at developing novel methods for the valorization of this abundant raw material [1]. One way of

• reported in Table 2, cyclic carbonate, catalyst and unreacted epoxide (for entries 10 and 11) were the only species detected by 1H NMR spectroscopy of the crude reaction product prior to purification by column chromatography. The moderate yield for propylene oxide (Table 2, entry 6) can be explained by