6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• enlargement via selective cyclopropane ring opening [46][47][48][49]. Consequently, the synthesis started from the previously described bicyclic silyl enol ethers 1α/β (Scheme 1) [50][51]. The two anomers of 1 were individually transformed into the trimethylsilyl (TMS)-protected sugars 2α/β by adapting and

• persilylated thymine in the presence of NIS (Scheme 2), followed by radical reduction of the iodide intermediate with tributyltin hydride (Bu3SnH) generated an anomeric mixture of nucleoside 6α/β with the β-anomer as major component (α/β ratio = 1:4.5 according to 1H NMR). The inseparable anomers of nucleoside

• 6α/β were subjected to the next reaction step, where the simultaneous desilylation and cyclopropane ring opening to the bicyclic fluoroenone 7 occurred. HF-pyridine smoothly facilitated this conversion. At this stage the two anomers of fluoroenone 7 were separable. The configurational assignment of

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• proceeded mostly in good to high yields (57–86% for the Ritter reaction and 35–89% for the Ullmann coupling). The Ritter reaction gave two anomers, which could be separated by column chromatography. The prepared ligands showed promising results (er of up to 84:16) in Tsuji–Trost reactions with diphenylallyl

• is hindered. In the literature this fact is used to explain the different reactivities between “armed” and “disarmed” glycosyl donors in glycosylation reactions [33]. Due to the fact that 9 can be attacked from two sides by nitriles, the oxazolines occur in two isomeric forms, the β-anomers (10) and

• the α-anomers (11), which were separated by column chromatography. No crystals suitable for X-ray crystallography could be obtained from the direct products of the Ritter reaction. To get a more polar molecule which is more appropriate to form crystals suitable for X-ray crystallography, a deprotected

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• equilibrium of both, α- and β-anomers (Scheme 2, right dashed box). However, full anomerization is often not observed as the rate and the extent of mutarotation depends on various parameters such as anchimeric effects of neighboring groups and the reaction conditions. Hence it has been frequently observed in

• employed acidic reaction partner can lead to predominant formation of the β-configured product, whereas stronger acidic reagents can favor the formation of the respective α-anomers. These findings can be explained by considering the two different reaction pathways A and B as shown above in Scheme 2. The

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

• under sila-Pummerer conditions [29][30]. We found that treatment of 12, obtained by oxidation of 11, with excess persilylated N4-acetylcytosine in the presence of TMSOTf as a Lewis acid gave an inseparable mixture of α- and β-anomers of 4’-thioDMDC derivatives 15 in good yield. Based on the study of the

• reacted with a nucleobase, giving a mixture of α- and β-anomers since the reaction might occur by the simple SN2 reaction. Thus, the reaction proceeded through both paths a and b in method A, but path a was predominant in the reaction of method B [45] (Figure 3). Nishizono et al. applied the hypervalent

• ). The hypervalent iodine-mediated glycosylation of 2,4-bis(trimethylsilyl)uracil (29) with glycal 124 gave an inseparable mixture of α- and β-anomers 125 (α:β = 1:2) in 51% yield as we expected. Compound 125 was then oxidized by treatment with mCPBA, followed by elimination of the resulting selenoxide

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• co-workers describe transformation of adenine hydrochloride and D-ribose into the corresponding nucleoside α- (4%) or β- (3%) anomers following “thorough grinding” and heating of the mixture they do not distinguish between mechanochemistry and thermochemistry effects [119]. Considering recent

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• Vorbrüggen coupling reaction [66], the synthesis of C-nucleosides typically gives a mixture of stereoisomers (α and β) at the anomeric carbon [48][49][54][62][67][68]. Since the naturally occurring nucleosides (and most biologically active nucleosides) are β-anomers, achieving 100% stereospecificity in C–C

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Diosgenyl 2-amino-2-deoxy-β-D-galactopyranoside: synthesis, derivatives and antimicrobial activity

• Henryk Myszka,
• Patrycja Sokołowska,
• Agnieszka Cieślińska,
• Andrzej Nowacki,
• Maciej Jaśkiewicz,
• Wojciech Kamysz and
• Beata Liberek

Beilstein J. Org. Chem. 2017, 13, 2310–2315, doi:10.3762/bjoc.13.227

• with acetic anhydride to give fully protected galactose 1 as an anomeric mixture. The α and β anomers (3:7 molar ratio) were identified by NMR. To synthesize bromide 2, we used TiBr4 as a bromination agent. Bromide 2 was obtained as a mixture of α and β anomers (1:4 molar ratio) and was used directly

• in the glycosylation. This mixture of 2 is chromatographically inseparable due to the highly reactive nature of the bromine group at the anomeric carbon, but, the anomers of 2 are readily distinguishable in the NMR spectrum (δ 6.65, d, J1,2 = 3.7 Hz for the α anomer and δ 6.35, d, J1,2 = 9.6 Hz for

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• mixture of two anomers (α:β = 2:1). Treatment of azido ester 5 with NaBH4 gave predominantly azidodiol 6 (66%) and small amounts of aminodiol 7 (5%). Application of LiAlH4 as the reducing agent afforded only compound 7 (Scheme 1). The former result may open, eventually, a new possibility for the

• washed with water (40 mL) and brine (40 mL), dried, concentrated, and the crude product was purified by column chromatography (hexanes/ethyl acetate 9:1) to yield 5 (0.32 g, 0.26 mmol, 86%) as a 2:1 mixture of α/β anomers (calculated by integration of the anomeric signals at δ: 6.34 and 5.63). 1H NMR

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• , equal amounts of α- and β-anomers were obtained. Also, when a glucosyl acceptor was employed, mainly the 1,2-cis-linked product was obtained. Valverde et al. also investigated succinoyl tethers [54], but their studies were mainly focusing on phthaloyl and non-symmetrical linkers described below. Among

• participating solvent acetonitrile that was unable to favor β-anomers, like in intramolecular glycosylations. Instead, complete β-selectivity could be achieved using glycosyl donors equipped with the participating group at C-2. A further mechanistic study of this work led to the appreciation of phthaloyl

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

• rationale remains elusive. To demonstrate that their conditions were viable in the presence of other hydroxy groups on the saccharides a small series of phenyl C-glycosides were synthesized (Table 5). In all cases the reaction was high yielding and perfectly stereospecific for both anomers even in the

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• the literature reported [19], and the structure was confirmed by MS and NMR. The α-anomers of 5 and 6 were the key impurities during the synthetic process. Pure compounds of 5’ and 6’ were prepared for the analytical references (Scheme 4). Compound 4a was converted to the corresponding arylzinc

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

• . This approach works for glucosides, mannosides, and galactosides and both, α- and β-thioglycosides [40]. It was shown by competition experiments that these tethered donors were even more reactive than the TBS-protected donors such as 20. This was particularly the case for the α-anomers as a

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• a ratio of α/β = 2:1. After separation of the anomers, pure methyl α-L-selenofucoside (1) was finally obtained after deprotection of the α-anomer in 25% over 5 steps from L-fucose (4). A selective methylation of the hydroxy group in position 2 requires prior protection of the cis-diol in position 3

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• ] were converted into the p-nitrophenyl carbonates 6a and 7a in good yields. The corresponding carbonate of per-O-benzoyl glucopyranose 8a [30][31] was obtained in only moderate yield and as a mixture of α and β anomers which was used without further purification. The carbonates were subsequently reacted

• with DBU under the same conditions as described above, giving 6b and 7b in 82% and 87% yield, and 8b as a mixture of α and β anomers in 48% yield. Encouraged by these results, we turned to evaluate the nucleophilicity of DBN towards p-nitrophenyl carbonate derivatives (Scheme 2). Next, the reaction of

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• -addition) through Ru-catalysed cycloaddition using an adapted procedure from the literature [16]. As the α- and β-anomers of furanoses are diastereomeric, in principle they show distinguishable NMR spectra. In consequence, the proportions of both anomers may be determined by NMR. In our case, the main

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

• oxazoline formation, the order of reactions was reversed, and triethylsilyl triflate (TESOTf)-catalyzed [58] acetolysis of the 1,6-anhydro bridge in 19 gave 42 (Table 1) as a mixture of anomers from which the α-anomer crystallized. TESOTf as a catalyst for acetolysis gave better results than sulfuric acid

• in terms of product purity. Hydrogenolysis of 42 on palladium in ethanol/HCl followed by acetylation of the amino group furnished the target acetylated 3-fluoro-D-GlcNAc 5 as a chromatographically separable mixture of anomers (Table 1). Addition of HCl was found necessary to effect a clean

• , TESOTf-catalyzed acetolysis and subsequent hydrogenation (Pd/C in a mixture of ethanol and acetic anhydride) was applied to obtain the target acetylated fluoro analogs (Table 1). Compound 21 was acetolyzed to 43 which was obtained as a mixture of anomers and characterized by NMR and finally hydrogenated

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• Rha2Me at δ 70.2–70.4 and Fuc at δ 68.1 were close to published data of the corresponding α-anomers (δ 69.4 and 73.6 for α- and β-Rha, δ 67.5 and 71.9 for α- and β-Fuc, respectively [19]); therefore, these monosaccharides were α-linked. The 13C NMR signals for C-3 of Fuc in 1 and 2 shifted significantly

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• , which usually exhibit a diminished glycosylation selectivity, were represented by L-arabinofuranosyl bromide 19 and D-xylopyranosyl bromide 20. The glycosylation of 6b with galactosyl, glucuronic acid methyl ester or lactosyl bromides 15, 17 and 18, proceeded also stereoselectively and the β-anomers of

• glycosides 25, 27 and 28 were isolated in good yields (50–68%) as the only products. The structures of all β-anomers (21a–c, 22, 23, 25, 27 and 28) were confirmed by the presence of a doublet of the anomeric proton with characteristic vicinal interaction constant 3J1,2 in the interval of 7.5–7.9 Hz in the 1H

• NMR spectra. The glycosidic bond between galactose and glucose in lactosyl bromide 15 was not affected under the examined conditions. On the other hand, the reaction of D-mannosyl and L-arabinosyl bromides 16 and 19 with 6b afforded solely α-anomers 26 and 29 as the 1,2-trans-glycosylation products

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• two anomers. In 2012, Xie and his group envisioned the use of α,α-dicyano olefins 90, as a vinylogous Michael donor in an asymmetric Michael addition to substituted 3-nitro-2H-chromenes 91 catalyzed by bifunctional thiourea catalyst 92 (Scheme 31) [50]. When R2 is an alkyl group the reaction resulted

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• , respectively. The anomers of 5 and 6 could not be separated by standard column chromatography though. Thiocarbamate 5 was previously mentioned in the literature [21], but due to the fast anomerisation and the relative instability of 1,3-oxazolidin-2-thiones it was never characterized. However, in our hands

• , anomers could easily be separated by chromatography after benzylation of 5 and 6 with BnBr and NaH to give the corresponding benzylated sulfanyloxazolines 7 and 8 which were air and moisture stable (see Supporting Information File 1 for full experimental details). Nevertheless, it should be noted that

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• 1H NMR signals of the acetamide group in derivatives 8, a 3:2 ratio of the anomers was determined, albeit without the exact assignment of anomeric configurations to particular anomers. In the context of the synthesis of the saccharide part of GnTs inhibitors, psicose derivative 7 was subjected to a

• both anomers were formed together with 3-acetamido-3-deoxy-4,5-O-isopropylidene-6-O-pivaloyl-D-psicose as a byproduct originating from isopropylidenation of the open-chain form of 9, only the α-anomer, namely 3-acetamido-3-deoxy-1,2-O-isopropylidene-6-O-pivaloyl-α-D-psicofuranose (10), was isolated in

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• ]. Only one enantiomer at 8-C was isolated, showing retention of stereochemistry. This would support the hypothesis that the difference in energies of the 6-membered ring anomers relative to a 5-membered ring is sufficient to drive the conversion of 3 to 4. Conclusion In this paper we have presented the

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• -phenylamino-1-deoxy-D-manno-heptulose 10 were obtained as pure α-anomers in 77% and 24% yield, respectively (Scheme 3). The low yield of compound 10 may be explained by the low pKa value (4.62) of aniline compared to a pKa of 8.15 for propargylamine, the latter being clearly more efficient as a nucleophile

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

• Agata Walczewska,
• Daria Grzywacz,
• Dorota Bednarczyk,
• Małgorzata Dawgul,
• Andrzej Nowacki,
• Wojciech Kamysz,
• Beata Liberek and
• Henryk Myszka

Beilstein J. Org. Chem. 2015, 11, 869–874, doi:10.3762/bjoc.11.97

• Chemistry To synthesize the parent diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside (7), the O-acetylated bromides 2a–d, chlorides 3a–d and (N-phenyl)trifluoroacetimidates 5a–d, α or β anomers, were examined (Scheme 1). These glycosyl donors were N-protected with trifluoroacetyl (TFA, a), 2,2,2

• demonstrated. To synthesize bromide 2b we used a procedure described by Ellervik and Magnusson for other glycosylations [46]. However, the bromide obtained by them was a mixture of α and β anomers whereas 2b is a pure α anomer (J1,2 4,0 Hz). Bromide 2b, identified as the α anomer, was also synthesized by