Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• nucleophilically attacks the intermediate forming the desired glycosidic product [22][23][24]. With the preactivation protocol, the donor activation and acceptor glycosylation occur in two distinctive steps. As a result, a unique chemoselectivity can be achieved with preactivation. Glycosyl donors and acceptors

• , affording glycoside 22 in 86% yield (α:β = 27:73, Scheme 6). This glycosylation strategy can be applied to a variety of glycosyl acceptors, including oxygen, sulfur, carbon and nitrogen nucleophiles (Figure 1) [36]. Even the unreactive N-(trimethylsilyl)trimethylacetamide could be efficiently glycosylated

• uronic acid in an α-selective fashion. A variety of azido hemiacetal glucoside donor and uronic acid thioglycosyl acceptor pairs were screened under preactivation conditions. The anomeric leaving groups of the acceptors had significant impacts on the glycosylation outcomes (Scheme 11a). When donor 54 was

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• methods (see Scheme 3).· Also noteworthy is the multistep solvent-free mechanochemical route to indium(III) complexes featuring aryl bis(imino)acenaphthene (Ar-BIAN) ligands [84]. Ar-BIAN ligands are versatile π-acceptors and have been widely employed for catalysis. These ligands are typically synthesised

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• high α-selectivity (α/β = 8:1). Interestingly, when the donor and acceptor positions on the peptide were reversed, such as conjugate 39, glycosidation of this compound produced disaccharide 40 in 75% yield albeit the stereoselectivity was entirely lost (α/β = 1:1). Galactosyl acceptors also showed a

• dramatic effect of the relative position of the donor and acceptor on the peptide sequence. Intriguingly, the stereoselectivity outcome was reversed (1.8:1 and 9:1) in comparison to glucosyl acceptors. When a similar concept was applied to mannosyl acceptor low 2:1 stereoselectivity was obtained regardless

• acceptors together [56][82]. The templated synthesis also falls into the general molecular clamping method. High stereoselectivity could be achieved with both flexible and rigid linkers (L1 and L2, Scheme 13). However, the use of the rigid BPA template core appears to be the key to ensure the high

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• investigated by using a variety of glycosyl donors 4–10 [34][35][36][37][38] containing C-2 participating groups to ensure 1,2-trans-glycoside formation (Table 2). Each glycosylating agent was reacted with D-glucose acceptors 2 (Table 2, entries 1–8) and 11 [39] (Table 2, entries 9–16) with a free hydroxy

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• -glycosylation, although their endogenous role is not to generate S-glycosides. Brazier-Hicks and colleagues have screened many A. thaliana Family 1 GTs with three acceptors, to identify O-GT, N-GT and S-GT enzymatic activities [29]. Among the 99 enzymes tested, 17 were able to use 4-chlorothiophenol as the

• acceptor. UGT74B1, involved in glucosinolate biosynthesis (see supra), was one of these 17 enzymes. Other studies have identified S-GT activities when assaying the catalytic promiscuity of O-GT with a wide range of aglycone acceptors (Figure 3). OleD from Streptomyces antibioticus has been the first

• reported O-GT to catalyse S-glycosylation on thiol acceptors [30]. Genetic engineering of this enzyme has also led to S-GT activities on several thiols. UGT73AE1 from Carthamus tinctorius was able to transfer glucose on a wide range of acceptors, including a S-containing compound, dichlorothiophenol [31

Conformational impact of structural modifications in 2-fluorocyclohexanone

• Francisco A. Martins,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2017, 13, 1781–1787, doi:10.3762/bjoc.13.172

• , the π*C=Y orbitals (Y = O, S and N) are better electron acceptors than the π*C=C in electron delocalization processes. These highlight the role of electrostatic and hyperconjugative effects on the conformational isomerism of the studied compounds. Two particularly clear trends are related to the NH

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• -oxygenation reactions above, also the introduction of a nitrogen-based functionality alpha to a carbonyl group can be achieved by several complementary strategies. One powerful option is to carry out Michael addition-initiated aziridination reactions of α,β-unsaturated carbonyl acceptors [18][138][139][140

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• acceptor) or via oxidative dehydrogenation in the presence of appropriate oxidants. In absence of hydrogen acceptors, post dehydrogenation the hydrogen is released as H2↑. Catalysts such as iridium pincer complexes, CuAl2O3, hydroxyapatite bound palladium and ruthenium hydride complexes have been harnessed

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

• position which could provide under the right conditions, regioselectively and stereoselectively 1,2-cis glycosides of a wide variety. The substrate scope is broad and even includes glycosyl phosphates and esters in addition to a host of alcohol acceptors (Scheme 8). Certainly the most important application

• donors screened in the study. The preparation of the phenyl galactothioside is shown in Scheme 15. The chemistry can be described as straightforward, however, the use of thiophenol is required which is highly toxic and odorous. 3.3.2 Regioselective glycosylation of unprotected acceptors: Another

• field. It is driven by the appeal of waste reduction in chemical synthesis that the use of stoichiometric amounts of reagents, unfortunately cause. Typical transition metals employed for promoting the glycosylation of protected acceptors using protected donors include Pd, Ni, Au, Rh, Ru, and Ti [61]. In

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• of sterols to and from membranes, this can be principally realized via vesicular traffic or via monomeric transfer. The latter mechanism requires the presence of donors and acceptors, respectively, due to the low water solubility of sterols. Nevertheless, the import and export of cholesterol is

• rather slow [34], wherefore membrane proteins have been proposed to facilitate these processes. One putative function of those proteins could be to relieve the presentation of cholesterol molecules on the membrane surface for a better binding to extracellular acceptors (see [35]). It can be hypothesized

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• are present in the triclinic unit cell, being associated by two N–H···N hydrogen bonds in which benzylamino NH bonds act as donors and aminide nitrogen atoms as acceptors. As expected, the triazolium-aminide moiety in 7a is planar. The comparison of the bond lengths in this moiety with those in nitron

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• acceptors forming mono- or poly(ADP-ribos)ylated proteins. Out of the 18 members identified, only four are known to synthesise the complex poly(ADP-ribose) biopolymer. The investigation of this posttranslational modification is important due to its involvement in cancer and other diseases. Lately, metabolic

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

• papilloma virus type 11 (HPV11) inhibitors. These 1-indanones 99 have been synthesized using a N-heterocyclic carbene-catalyzed [4 + 1] annulation utilizing phthalaldehyde (97) and 1,2-diactivated Michael acceptors 98 (Scheme 31) [55][56]. 1.1.5 From ketones and 1,2-diketones: Another interesting approach

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• the dyes into the major groove led them find a better orientation than in the minor groove, with respect to the DNA helix with enhanced fluorescence intensities. The dyes D1–D4 as energy donors were combined with dyes D5–D9 as energy acceptors (Scheme 3). This approach follows our concept of “DNA/RNA

• absorption of the acceptors show broad spectral overlays and therefore selective excitation is not possible. For each of the previously described dye combinations, we probed all four combinations of arabino- and ribo-configured donor strands (DNA2a and DNA2r) with acceptor strands (DNA3a and DNA3r). This

• /lysosomal vesicles. The fluorescence of the energy donors, D1, D2 and D4 (Figure 2, left column), as well as the fluorescence of the energy acceptors, D5 and D8 (Figure 2, middle column), could be detected showing that fluorescence energy was transferred from the donor to the acceptor in the respective FRET

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• acceptors. However, glycosylation with heavily silylated carbohydrate derivatives is comparatively new, and so is the significance that silyl groups have on the stereoselectivity and reactivity in glycosylation reactions [4]. These findings, which most have occurred in the last decade, will be reviewed here

• reactivity of the corresponding glycosyl donors. The increased reactivity is very clearly displayed when TBS or TIPS-protected thioglycosyl donors are mixed with benzylated thioglycoside acceptors under activating conditions (Table 1). The benzylated thioglycosides 21 and 26, normally termed ‘armed’ due to

• thioglucoside 45 was found to be much less reactive than 20 and only couples to armed donor/acceptors in low yield (Figure 4) [24]. This is analogous to the effect of the very similar benzylidene group, which is deactivating the donor partially due to locking the structure in an unreactive conformation and due

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

• acceptors and also act as electron-withdrawing substituents when attached to other aromatic rings thus enhancing benzene’s ring C–H hydrogen bonding [29][30][31]. Recent studies by the Flood group and the Craig group suggested that receptors containing arylated 1,2,3-triazoles could form stable

• containing a halogen (I···N) bond [70]. When chiral organohalides form halogen bonds with chiral acceptors, diastereomeric complexes may be formed. Thus, in 1999, Resnati reported the resolution of racemic 1,2-dibromohexafluoropropane through halogen-bonded supramolecular helices (Scheme 13) [69]. When

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• -unsaturated acceptors [27][28][29]. Indeed, activation of aromatic α-diketones may occur through a double electron-transfer (ET) process triggered by the carbamoyl anion derived from N,N-dimethylformamide (DMF) solvent with catalytic base, which generates an enediolate anion as key reactive species of

• confirmed by the higher residence time (276 min) required to reach satisfactory conversions. Again, benzil 1d proved to be completely ineffective in the addition to α,β-unsaturated acceptors as well (Table 5, entry 7). Conclusion In summary, we have disclosed a practical continuous-flow procedure for the

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• significant number of H-bond donors and acceptors [39]. Indeed, CDs violate three criteria of the Lipinski’s rule: i) no more than 5 H-bond donors, ii) no more than 10 H-bond acceptors, iii) a molecular mass less than 500 g/mol, and iv) an octanol–water partition coefficient (log P) not greater than 5 [40

• concentrations of modified β-CDs result in rates of cell cholesterol efflux far in excess of those achieved with physiological cholesterol acceptors such as high-density lipoproteins (HDL). Indeed, plasma levels of HDL are inversely associated with cardiovascular morbidity and mortality because this lipoprotein

• with the cholesterol acceptors, the authors proposed that the cholesterol efflux from serum monocytes is the main mechanism and is probably an effective means of inhibiting the development of atherosclerotic plaques. In 2015, Montecucco et al. reported the anti-atherosclerotic action of KLEPTOSE

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• -workers appeared, Wenwei Lin and a co-worker published conceptually similar catalytic Wittig reactions that were based on their previous research regarding related non-catalytic phosphine-mediated base-free Wittig reactions (Scheme 10) [28]. They started with Michael acceptors 36 to generate products 37

Synthesis and characterization of fluorinated azadipyrromethene complexes as acceptors for organic photovoltaics

• Forrest S. Etheridge,
• Roshan J. Fernando,
• Sandra Pejić,
• Matthias Zeller and
• Geneviève Sauvé

Beilstein J. Org. Chem. 2016, 12, 1925–1938, doi:10.3762/bjoc.12.182

• Homoleptic zinc(II) complexes of di(phenylacetylene)azadipyrromethene (e.g., Zn(WS3)2) are potential non-fullerene electron acceptors for organic photovoltaics. To tune their properties, fluorination of Zn(WS3)2 at various positions was investigated. Three fluorinated azadipyrromethene-based ligands were

• substitution at the pyrrolic phenylacetylene moieties. The later complexes are expected to be stronger electron acceptors than Zn(WS3)2, and may enable charge transfer from other conjugated polymer donors that have lower energy levels than poly(3-hexylthiophene) (P3HT). Keywords: dye; fluorine; near-IR

• chelation [1][2][3][4]. BF2+-chelated ADP derivatives (Figure 1b) in particular have drawn interest for photodynamic therapy, bio-imaging and light harvesting applications [5][6][7][8]. We have shown that derivatives of Zn(ADP)2 are promising electron acceptors for organic photovoltaics (OPVs) [9][10]. A

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• dithiol acetal side product 9. Inspired by the results obtained in the synthesis of S-2-deoxyglycosides, we explored the use of numerous alcohols as acceptors in order to directly synthesize O-2-deoxyglycosides from glycals. In Table 2 the reaction of glucal 1 and benzyl alcohol (12) under similar

• attempted to extend the scope of the glycosylation of 3,4,6-O-acetyl- and O-benzylglucal (1 and 3) with other acceptors (Table 3). Under the optimized conditions, glucal 1 reacted with numerous primary, secondary, and tertiary alcohols, including methanol (13), allyl alcohol (14), isopropanol (15), tert

• -glucosides were formed in their corresponding products 33 (71%, 5:1, Table 3, entry 9) and 34 (79%, 4:1, Table 3, entry 10). For the use of monosaccharides as acceptors, primary monosaccharides 22 and 23 gave disaccharides 35 (80%, Table 3, entry 11) and 36 (78%, Table 3, entry 12) respectively in high

Synthesis and characterization of benzodithiophene and benzotriazole-based polymers for photovoltaic applications

• Desta Gedefaw,
• Marta Tessarolo,
• Margherita Bolognesi,
• Mario Prosa,
• Renee Kroon,
• Wenliu Zhuang,
• Patrik Henriksson,
• Kim Bini,
• Ergang Wang,
• Michele Muccini,
• Mirko Seri and
• Mats R. Andersson

Beilstein J. Org. Chem. 2016, 12, 1629–1637, doi:10.3762/bjoc.12.160

• was calibrated by measuring the ferrocene/ferrocenium (Fc/Fc+) redox peak. The HOMO and LUMO energy levels of the polymers and electron acceptors were calculated from the peak values of the third scans by setting the oxidative peak potential of Fc/Fc+ vs the normal-hydrogen electrode (NHE) to 0.630 V

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

• are biosynthesised in seven principal ways (Scheme 2). Those comprise nucleophilic addition of a hydroxy group to electrophiles like epoxides 4, carbonyl groups 6 or Michael acceptors 9, potentially followed by further processing (a–c in Scheme 2). Lactones 12 are formed by transacylation of a

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• the enantioselective reduction of α-substituted conjugate addition acceptors, including catalytic hydrogenation, multiple reviews have already appeared on this topic, and therefore asymmetric catalytic reduction will not be covered here [11][12][13]. Conjugate addition followed by terminal

• high yield and enantioselectivity for both α-alkyl and α-aryl conjugate addition acceptors. Alkyl substrates reacted smoothly at 25 °C (90–98% yield, 90:10 to 95.5-4.5 er) even when R was a more sterically demanding isopropyl or cyclohexyl group. Aryl substrates required lower reaction temperatures and

• additions to other classes of Michael acceptors only being reported more recently. While many examples using sulfur and carbon nucleophiles have been reported, the addition of other heteroatom nucleophiles remains relatively unexplored. This approach for the synthesis of tertiary carbon stereocenters