De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• , stereogenic centers and stereoelectronic effects combine to dictate the “topology” or overall fold of a macrocycle. The structure of β-D-galactose-[13]-macrodiolide 3 [9], derived from X-ray data, originated this line of investigation. It showed that both esters and the epoxide unit are each composed of four

• coplanar atoms that significantly reduce the number of freely rotatable bonds in the molecule [9][10][12][23][24][25] and rigidify its structure. The consequence is that the esters, alkene and epoxide units are not coplanar, but are set at angles to each other (Figure 2 ). The result is a twist in the

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• dichloromethane and subsequent acidic epoxide hydrolysis produced the syn-diol rac-39. The following protection of diol rac-39 as its acetonide and the primary hydroxy group deprotection using sodium methoxide afforded alcohol rac-40 in good yield (43% over 5 steps). Next, Swern oxidation of the primary hydroxy

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• chiral auxiliary through ozonolysis followed by protection of the side chain as TBDPS ether afforded cyclopentanone 155. Saegusa–Ito oxidation followed by epoxidation of the formed enone gave 156 as the major isomer (dr 9:1). Regioselective reductive opening of the epoxide with Na[PhSeB(OEt)3] produced

• oxa-Pictet–Spengler reaction from 2,6-dihydroxybenzoic acid 173 and ketal aldehyde 174 as key building blocks (Figure 10). The 2,6-dihydroxybenzoic acid 173 is accessible by opening of epoxide 175 as chiron with a suitable nucleophile. The ketal aldehyde 174 would be derived from butenolide 176

Comparing kinetic profiles between bifunctional and binary type of Zn(salen)-based catalysts for organic carbonate formation

• Carmen Martín and
• Arjan W. Kleij

Beilstein J. Org. Chem. 2014, 10, 1817–1825, doi:10.3762/bjoc.10.191

• [salphen = N,N’-phenylene-1,2-bis[salicylidene]imine] (Figure 1, 1) combined with a nucleophilic ammonium halide salt [26][27], or an analogous bifunctional system (Figure 1, 2) containing a Lewis acidic and nucleophilic center within the same molecule [29]. Mechanistic investigations for these CO2/epoxide

• NBu3 able to activate CO2 whereas the other molecule helps to ring-open a coordinated epoxide. This activation mode differs from one reported for the binary system based on Al complex 3/NBu4I (Figure 1) [37] and the first-order dependence with respect to each catalyst and co-catalyst displayed when the

• are the efforts from Coates and co-workers [44] and the kinetic studies described by the group of Williams [45]. In each of these latter cases a binuclear mechanism was proposed for the copolymerization reaction of CO2 and epoxide, establishing a second-order dependence for mononuclear Zn complex 7

Copolymerization and terpolymerization of carbon dioxide/propylene oxide/phthalic anhydride using a (salen)Co(III) complex tethering four quaternary ammonium salts

• Jong Yeob Jeon,
• Seong Chan Eo,
• Jobi Kodiyan Varghese and
• Bun Yeoul Lee

Beilstein J. Org. Chem. 2014, 10, 1787–1795, doi:10.3762/bjoc.10.187

• /epoxide copolymerizations, shows high activity for propylene oxide/phthalic anhydride (PO/PA) copolymerizations and PO/CO2/PA terpolymerizations. In the PO/PA copolymerizations, full conversion of PA was achieved within 5 h, and strictly alternating copolymers of poly(1,2-propylene phthalate)s were

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• alcohol, aziridine, aldehyde and epoxide halogenation reactions from which the desired products are easily isolated and the phosphine oxide byproduct is readily recycled. Results and Discussion Rasta resin 16 was prepared by oxidation of 14, which was prepared as previously reported [28], using H2O2

• the reaction mixture was washed and dried, and then used directly for the next reaction cycle. Excellent yields were successfully obtained for 8 runs with both 4H and 8B. Gel-phase 31P NMR analysis of 16 recovered at the end of these experiments indicated no change in its oxidation state. Epoxide

• halogenation reactions With the versatility and excellent reactivity of 16 established, we were encouraged to examine our method in the epoxide halogenation reactions shown in Scheme 2. Since these reactions require the use of a base, we designed a bifunctional rasta resin, RR-NBniPr2-PPh3=O 18 (Scheme 5

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• sublimated under vacuum to give 24.1 g of acid 1 in 49.0% yield [17]. 1H NMR (500 MHz, CDCl3) δ 4.35 (t, J = 4.5 Hz, 1H), 2.68 (m, 2H), 2.08 (t, J = 2.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 177.5, 77.7, 71.9, 68.5, 24.4. Synthesis of 2-hydroxy-4-pentynoic acid (1). Synthesis of 1 via epoxide ring opening with

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• microcontact printed on epoxide-terminated self-assembled monolayers. Successive prints resulted in simple microarrays of two carbohydrates. The selectivity of the synthetic lectin was investigated by incubation on the immobilized carbohydrates. Selective binding of the synthetic lectin to immobilized NANA and

• HisHis towards immobilized NANA in comparison with the glycosides of glucose (Glc), galactose (Gal) and mannose (Man) (Figure 1). In this study, we exploit the epoxide ring opening reaction of amine-tethered carbohydrates on epoxide-terminated SAMs [42] to print carbohydrate microarrays on silicon and

• glass substrates. Epoxide-terminated SAMs are particularly versatile for the fabrication of biological arrays [43][44] and we have recently demonstrated that epoxide-terminated substrates are easily modified using µCP [45]. The incubation of the synthetic lectin FITC-HisHis as well as two natural

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• converted only up to 4% to get a mixture of 2,3-epoxynerol (6) and diepoxynerol (8) at a ratio of 58:42. V286A and V286F catalysed the oxidation of geraniol (1) to a mixture of epoxides 5 and 7 as in the case of V286L. Two epoxide products appeared at a ratio of 59:41 (V286A), and only 6% substrate

• -hydroxygeranylacetone (11, 8%) and the epoxide 9,10-epoxygeranylacetone (17, 9%). Similar to the conversion of geraniol (1), the regio- and chemoselectivity of geranylacetone oxidation catalysed by the mutants was different compared to the wild type enzyme. The product analysis revealed a strong preference of all three

• mutants for the formation of C7-hydroxylated compound 11 as the main product. Variant V286L produced 44% of 7-hydroxygeranylactone (11) as well as the compounds 13 (18%) and 15 (35%). Substrate epoxidation leading to the epoxide 17 was much slower compared to the wild type: this product accounted to less

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• effect an epoxidation of 8. Application of substoichiometric amounts of oxidant (Oxone®) delivered the isomeric mono-epoxides 9 and 10 as the main constituents, along with minor amounts of the bis-epoxide 11. Of note, on work-up 9 was observed to undergo partial cyclization to the desired tetrahydrofuran

Metal and metal-free photocatalysts: mechanistic approach and application as photoinitiators of photopolymerization

• Jacques Lalevée,
• Sofia Telitel,
• Pu Xiao,
• Marc Lepeltier,
• Frédéric Dumur,
• Fabrice Morlet-Savary,
• Didier Gigmes and
• Jean-Pierre Fouassier

Beilstein J. Org. Chem. 2014, 10, 863–876, doi:10.3762/bjoc.10.83

• ; Scheme 11) [64]. All these described systems, producing radicals, cations or radical cations, allow efficient CP and FRPCP of cationic monomers, FRP of acrylates, simultaneous radical/cationic polymerization of epoxide/acrylate blend. The reactions can be carried out (see in [45][46][47][48][49][50][51

• ][52][53][54][55]) in formulations containing multifunctional synthetic epoxides, acrylates, monomers/oligomers or epoxide/acrylate blends (renewable raw or modified materials are usable to some extent) with lights extending from the UV to the red, using polychromatic or monochromatic light sources

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• initially-formed (E,E,E)-triene undergoes stereospecific epoxidation to a tri-epoxide and subsequent ring-opening and cyclisation to generate the polyether rings. This model has been confirmed and extended (Scheme 1) by the results of more recent work in which specific genes have been disrupted or deleted

• a transferase (MonKSX) transfers the chain to a discrete acyl carrier protein (MonACPX) [20], both of these proteins being encoded within the monensin gene cluster [16]. The flavin-dependent epoxidase MonCI then catalyses three stereospecific epoxidations to give the tri-epoxide 3, which then

• undergoes a cascade of ring opening/closing catalysed by the combined action of the unusual epoxide hydrolases MonBI and MonBII, to give the putative protein-bound intermediate dehydroxydemethylmonensin. The next steps, catalysed respectively by the cytochrome P450 hydroxylase MonD and the methyltransferase

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• control [58]. The configuration was determined by the high coupling constant (JH4/H5 = 12.6 Hz) indicating the trans-diaxial orientation of H4 and H5. Silylation of the primary hydroxy group afforded compound 84 that was converted into the epoxide with complete stereocontrol [59]. The epoxide underwent

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• followed by reductive epoxide opening furnished the desired alcohol 73 [72]. Alcohol-directed 1,4-reduction using LiAlH4 [73] followed by ether formation gave methyl ether 74. Reduction of the remaining ketone moiety gave the equatorial alcohol exclusively. Ortho-lithiation followed by the addition of

• ] applied the DVCPR in their total synthesis of gelsemine (146, see Scheme 20 and Scheme 21). Starting from bicycle 160 [140] epoxidation using mCPBA furnished epoxide 161 [141][142], which could be converted into vinylcyclopropanecarbaldehyde 162 upon rearrangement. Olefination using HWE-reagent 163

• , see Scheme 22) [152], isolated from the leaves of Gelsemium elegans was accomplished by Fukuyama and coworkers [153][154]. Starting from furfuryl alcohol (179) an epoxide initiated Achmatowicz reaction [155] took place to give α,β-unsaturated pyrane 180. Next in line was an enzyme catalyzed dynamic

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• disclose if the substituents of the epoxide are cis or trans-configured. The observed absolute differences for calculated versus NOE-derived distances/calculated distances (Table 2) suggested a trans-configuration for the epoxide (MAE of 4.7% vs 20.7% for cis-isomer) ring. The next step was the analysis of

• the four diastereoisomers 2a,b,e,f endowed with the epoxide moiety in a trans-configuration, by comparing the experimental vs the calculated distances (Table 3). In Table 3 only a subset of all values was used for the stereochemical structure elucidation, more specifically, the values where DFT

• consistent with anti-1,2-diol type C. Therefore the 7R,8S configuration is assigned. Notably, considering the plausible biogenetic interconversion of an epoxide and a diol, the above absolute configuration at C-7 and C-8 of plakilactone G is in full agreement with the trans-epoxide 2b. Having assigned the

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• was reacted in a ring-opening polymerization with the primary amine α-amino-ε-caprolactam (8). 8 was synthesized by cyclization of lysine (7) (Scheme 2). Hence, an increase of the reactivity of the primary amino group towards the epoxide function compared to the amino groups in native lysine was

• monitored. The spectrum of 6 exhibits weak bands at 1253 and 895 cm−1, which can be assigned to the C–O-stretching vibration and the symmetric ring deformation vibration, respectively, of its epoxide groups. On curing at 50 °C, a broad band between 3100 and 3600 cm−1 appears which is caused by hydrogen

• bonded hydroxy stretching vibrations originating from epoxide ring opening. The epoxide bands seem to vanish after curing, which is a sign for high conversion. However, due to overlaps of broader bands in adjacent areas, no clear statement can be made in this regard (Figure S5, Supporting Information

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• diglycidyl ether to give novel oligomeric thermoresponsive epoxide–amine adducts. These oligomers exhibit a lower critical solution temperature (LCST) behavior in water. The solubility properties were influenced with randomly methylated β-cyclodextrin (RAMEB-CD) and the curing properties of the amine–epoxide

• mixtures were analyzed by oscillatory rheology and differential scanning calorimetry, whereby significant differences in setting time, viscosity, and stiffness were observed. Keywords: amino acids; curing properties; cyclodextrin; epoxide–amine oligomers; LCST; Introduction Many partially hydrophobic

• resins exhibit poor solubility in water [15][16][17]. Accordingly, epoxide–amine polymers are not yet deeply investigated in respect to LCST behavior [18][19]. At present, most available bio-based and water soluble epoxy resins are expensive and use petroleum-based curing agents [20]. Thus, in the

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• ]-Wittig rearrangement, a diastereoselective epoxidation, and a microwave assisted transannular epoxide opening reaction. It is also noteworthy that the starting material 55 contains an extraneous fluorine atom which is deleted during the synthetic sequence; this approach takes advantage of the often low

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• , anthranilate is converted to 3-aminosalicylate by a multicomponent oxygenase, AntHIJKL [33][34]. The anthraniloyl-S-AntG carboxylic acid-CoA thioester undergoes a never before seen 1,2-shift. Spiteller and colleagues suggested that AntHIJKL promotes this reaction via an epoxide intermediate similar to a

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• at C6 could not be clarified. For the epoxide moiety of curvulide A, only the relative configurations at C4 and C5 were elucidated based on H,H-coupling constants (Figure 1) [30]. So far, two syntheses of stagonolide E have been published, which both rely on asymmetric synthesis for establishing both

• transition-state model, no reaction occurred after 2 d with L-(+)-DET, and the starting material could be recovered nearly quantitatively. In contrast, the use of D-(−)-DET led to the formation of an epoxide 39b in 58% yield. A comparison of the analytical data of 39b with those reported for curvulide A

• ° in the case of the diastereomeric epoxide 39b, and this value fits well to the observed 3J(H5–H6) value (Figure 2) [65]. Conclusion In summary, we synthesized the naturally occurring ten-membered lactones stagonolide E and curvulide A, starting from the ex-chiral pool building block (R,R)-hexa-1,5

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• PMB-protected 3-hydroxypropanal via Horner–Wadsworth-Emmons olefination, reduction to the allylic alcohol and Sharples epoxidation [8] (Scheme 2). Subsequent Cu-catalyzed epoxide-opening using methylmagnesium bromide [9] produced an inseparable mixture of 1,2- and 1,3-diol products, which upon

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• in dry CH2Cl2 at –10 to –23 °C for 2 h, the desired epoxide (2R,3R)-4 was obtained in 93% yield and 88% ee. The ee was determined by HPLC analysis of its corresponding TBDPS ether. This result compares well with the ones reported in the literature: 77–95% yield and 81–95% ee [17][18][19][20][21

• ]. According to Sharpless et al. [18], 5 mol % of Ti(OiPr)4 and 7.5 mol % of DIPT were used, so at least 20% excess of tartrate ester in order to obtain the maximum enantiomeric excess. The use of freshly distilled DIPT and Ti(OiPr)4 was important to obtain consistently 88% ee. With epoxide (2R,3R)-4 at hand

• the literature [8][9]. Starting from nerol, Sharpless asymmetric epoxidation afforded the epoxide (2S,3R)-4 in a disappointing 74% ee, a result which is nevertheless in accordance with the reported values: 70–94% [25][26][27][28][29][30] (Scheme 4). Applying the same ring-opening reaction to epoxide

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• presence of sodium ethoxide delivers epoxide 1.87. The material is next subjected to hydrogenolysis using Pd/C in methanol with a 1 bar hydrogen pressure to reductively ring open the epoxide. Finally, the transformation of the alcohol to the mesylate 1.88 occurs under standard conditions. In order to

• 1.119, which is first alkylated with epichlorohydrin (1.20) [63] (Scheme 22). The resulting epoxide 1.121 can then be ring opened with methanol in the presence of a tin Lewis acid yielding alcohol 1.122, which when subjected to Jones-oxidation conditions and Raney-Ni-mediated hydrogenation furnishes in

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• clean and gives the enone 2 in good yield along with minor amounts of the corresponding allyl alcohol 3 and the epoxide 4a. This successful conversion of theaspirane (1) encouraged us to investigate the oxidation of other spirocyclic terpenoids. Many oxidized spiroethers are valuable flavor compounds or

• the literature protocol using m-chloroperbenzoic acid. The major epoxide 4a was obtained in good yield and a diastereoselectivity of 11:1. Isomerisation of epoxide 4a to allyl alcohol 22 was reported with aluminium triisopropoxide at 140 °C [46]. However, in our hands this procedure gave only complex

• detected similar oxidation products with PSA and rationalize their formation by an initial epoxidation of the endocyclic double bond to give the allyl epoxide 25, which might then be hydrolyzed to two diastereomeric alcohols 26a and 26b. The latter reaction is known for similar allyl epoxides under