β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• ; epoxide thiolysis; β-hydroxy sulfides; sulfur-containing natural products; Review 1. Introduction Organosulfur compounds are widely distributed in nature, with marine organisms being the richest sources of these, since sulfur, as the sulfate ion, is the second most abundant anion in sea water after

• . Regioselective epoxide ring opening and 1,2-difunctionalization of alkenes are the commonly employed routes in the synthesis of such compounds. Both strategies are discussed below. 3.1 Synthesis of β-hydroxy sulfides via regioselective ring opening of epoxides The considerable ring strain present in epoxides

• thiols to give various β-hydroxy sulfides in good yields (Scheme 1) [20]. Both aryl and alkylthiols were found to be capable of opening the epoxide ring under the reaction conditions, and with respect to the epoxides, cycloalkane, alkene and 1-substituted alkene oxides were all amenable to the reaction

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• , the PMB-protected epoxide 121 was converted to diene 122. The dihydropyran ring of 123 was constructed by RCM of 122 catalyzed by a Grubbs 1st generation catalyst. The isomerization of the double bond in 123 by treatment with a Wilkinson catalyst under basic conditions afforded glycal 124 (Scheme 16

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• reaction in the following order: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein−Ponndorf−Verley reduction, aza-Diels−Alder and epoxide ring

• exhibited the best result. Aza-Diels–Alder and epoxide ring-opening reaction Manoury et al. have very recently reported facile synthesis of an enantiomerically pure inherently chiral calix[4]arene phosphonic acid (cR,pR)-121 from the readily available (cS)-enantiomer of calix[4]arene acetic acid 119 or its

• important transformations: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein–Ponndorf–Verley reduction, aza-Diels–Alder and epoxide ring-opening

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• pseudo-high-dilution conditions to afford 20 and 21 as described previously [16]. Then the diol was transformed into the epoxide following a three-step one-pot reaction as extensively used in the synthesis of cryptophycin analogues [46]. Cryptophycin analogues 22 and 23 were obtained in good purity after

• magenta. Docking of 22 to the vinca domain of β-tubulin. Surface and backbone of β-tubulin are shown in blue, GDP in yellow. No hydrogen bond formation was detected. The orientation of the azidoethoxy-ethoxyethyl substituent prevents the inhibitor from the correct interaction with the protein. The epoxide

• and benzyl group of subunit A are pointing away from the binding pocket. Docking of 24 to β-tubulin. Surface and backbone of β-tubulin are shown in blue, GDP in yellow. H-bonding (yellow dots) was detected with Lys176 and Asp179 in magenta. The benzyl group and the epoxide of subunit A are directed

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• -catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc). Keywords

• stereocenter on C4, resulting in the desired cis-selective epoxide opening and therefore, galacto-configured azido alcohols 7a and 7b (≥95% de) [22]. Initial limitations in reaction size and yield could have been overcome by switching the solvent from THF, as described in the Miyashita protocol, to EtOH. This

• approach opens up new perspectives for additional modifications: meso-tartaric acid as possible starting material or different epoxide opening protocols, as well as, the selective isotopic labelling are only a few to mention. This convertible synthetic route brings us a step closer to access the whole

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• epoxide with phenylboronic acid was realized with 2% of pincer catalyst, the rate was 100 times higher for the water-based micellar system compared to the same reaction in organic solvent with the unsupported Pd-complex. A 100 times lower amount of catalyst was also loaded (0.02%), and still the reaction

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• with DIBAl-H to 26 that was converted into the epoxide 27a by Sharpless epoxidation with (+)-L-DET. Treatment with TBSOTf and Hünig’s base resulted in opening of the epoxide with concomitant hydride migration to yield 28a. The stereochemical course for this reaction has been reported by Jung and

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• substituents is of interest. Here we describe optimisation efforts in the synthesis of anti-2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syn-diastereomer. Both targets were synthesised using an epoxide opening strategy. Keywords: acetal isomerization; deoxyfluorination; epoxide

• -difluorobutane-1,4-diol (anti-5) starting from commercially available cis-but-2-ene-1,4-diol (Scheme 1) [17]. The vicinal-difluoride group was introduced by a two-step sequence, with initial nucleophilic epoxide [18] opening by a fluoride source [19], followed by nucleophilic deoxyfluorination [9][10][11]. In

•  1 was high-yielding [17], two disadvantages were apparent. First, the epoxide opening takes 2.5 days at 115 °C and uses an expensive fluoride source (Landini’s reagent [18]: Bu4NH2F3). It was found that Bu4NH2F3 made in-house gave significantly reduced yields. Second, the use of the benzyl ether

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