Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• sugar sensors [43][44][45], and Anthony Czarnik had published his landmark treatise “Desperately Seeking Sensors” [72]. These three individuals are the true fathers of “Supramolecular Analytical Chemistry”, even if our group later introduced this terminology [73]. Sensing a paradigm shift Whereas

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• environment only. The secondary carbon substitution results in inversion in the reaction centre which changes the sugar moiety from glucoside to mannoside, altroside or alloside making those derivatives CD-based cyclic oligosaccharides and not CDs. The design of green synthetic methods for the bulk

Polydisperse methyl β-cyclodextrin–epichlorohydrin polymers: variable contact time ¹³C CP-MAS solid-state NMR characterization

• Isabelle Mallard,
• Davy Baudelet,
• Franca Castiglione,
• Monica Ferro,
• Walter Panzeri,
• Enzio Ragg and
• Andrea Mele

Beilstein J. Org. Chem. 2015, 11, 2785–2794, doi:10.3762/bjoc.11.299

• good line-shape fitting was obtained for all carbons of the sugar ring (C1–C5) and C6 for CRYSMEB, while for the three polymers the C6 signal is strongly overlapped with the epichlorohydrin resonances, consequently this line was not analyzed. The TCH values extracted from fitting the exponential rise

• carbon atoms show similar TCH values (Table 2, column 3). Similar results are observed for the three polymers, as shown by the values of columns 5, 7 and 9 in the order. For polymers D1 and D3, the TCH values of the β-CD sugar moiety are decreased with respect to that observed for native CRYSMEB, while

• for polymer D2 the opposite trend is observed. The emerging overall picture is that the polymerization can significantly change the response of the cyclodextrin macro-ring C atoms to the cross-polarization with respect to the pristine CRYSMEB. In detail, the sugar ring C atoms show TCH values

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• advantage of a chiral (R)-BINOL-bridge to link the two aromatic acids and obtained the coupling product with excellent stereocontrol (up to 100% de) (Scheme 1) [16][17][18][19]. In 1998, Martin et al. [20] applied this strategy to the asymmetric intramolecular biaryl coupling of sugar derivatives carrying 2

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

• formation and ring opening as well as reversion of the hydroxy group on the sugar ring. Jeong and co-workers [38][39][40] synthesized fluorine-substituted ribofuranose but isolation required a challenging separation. Therefore, the synthetic challenges for preparing 3’-fluorine modified sugars and

• ). 6-Methylpurine (28) was synthesized from 6-chloropurine according to the reported protocol [44]. Compound 28 was silylated with BSA and glycosylated with the 3’-fluoro-sugar 25 to provide the desired compound 29 in 78% yield. Subsequent deprotection furnished the targeted novel fluorine modified 6

Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale

• Janne Weisell,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237

• , 1H), 4.34–4.23 (m, 2H), 4.08–4.00 (m, 2H), 3.24 (q, J = 7.0, 16H, from triethylammonium salt), 2.30 (t, J = 6.5, 2H), 1.69 (s, 3H), 1.31 (t, J = 7.5, 24H, from triethylammonium salt). C=CH2 signals and one “sugar” proton signal under HDO-line at 4.8. 13C NMR (D2O) δ 158.5, 155.7, 152.1, 146.2, 142.8

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

• western countries, of people with obesity and type-II diabetes has pushed the food industry to develop new low calorie sweeteners, better known as sugar substituents. Among all artificial sweeteners so far developed: aspartame, saccharin, acesulfame K and sucralose are undoubtedly the most popular

• . However, questions regarding the safety of these sweeteners are still largely argued from the scientific community [1]. Thus, the discovery of new sugar substituents has become a target of food industry, to this regard new sweet-tasting natural products might offer a valid alternative to the artificial

• , in honor of the Spanish scientist, this natural product was called hernandulcin [6]. Hernandulcin is the first strongly sweet sesquiterpene, making it a breakthrough discovery in the field of natural sugar substitutes. It turned out that 1, which belongs to the family of bisabolanes, is more than

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• , Japan), and lyophilized to obtain Lac-β-CyD. The reaction was monitored by TLC (silica gel F254, Merck, Whitehouse Station, NJ). Eluent: methanol/water 9:1 (v/v), indicator: p-anisaldehyde for sugar and ninhydrin for amino groups. The Lac-β-CyD gave 1H NMR spectra consisting of protons of both β-CyD and

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

• synthesis of fused medium-sized rings has been reported by Ghosh and co-workers [41] via a sequential diastereoselective DA reaction and a RRM protocol. A variety of sugar-based norbornene derivatives provide an entry to various functionalized bicyclic sugar derivatives containing 7–9 membered rings. To

• protocol for the synthesis of bicyclic sugar derivatives. ROM–RCM sequence of the norbornene derivatives 186 and 187. RRM approach toward highly functionalized bridge tricyclic system. RRM approach toward highly functionalized tricyclic systems. Synthesis of hexacyclic compound 203 by RRM approach. RRM

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• give the carboxyl derivative 12b (reaction performed in acetonitrile containing 1% H2O v/v) or to link it to a sugar, like glucose to give the hybrid compound 12c (reaction performed in dry acetonitrile containing glucose). Both derivatives were significantly more soluble in aqueous solutions than the

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

• unknown [7]. In general, GTs transfer sugar nucleotide donors onto suitable acceptors during the biosynthesis of glycans and glycoconjugates [8]. Both donor and acceptor substrates are recognized by GTs binding pockets. For instance, in the course of biosynthesis of complex and hybrid oligosaccharides

• complexity of the GnTs catalytic mechanism. The main reasons originating from the complex character of the catalytic mechanism which complicate the search for GnTs inhibitors are a) participation of four components in the transition state (sugar donor, acceptor, nucleotide and metal co-factor), b) weak

Qualitative evaluation of regioselectivity in the formation of di- and tri-6-O-tritylates of α-cyclodextrin

• Keisuke Yoshikiyo,
• Yoshihisa Matsui and
• Tatsuyuki Yamamoto

Beilstein J. Org. Chem. 2015, 11, 1530–1540, doi:10.3762/bjoc.11.168

• the C(6)-OH on the adjacent glucopyranose in a counter-clockwise direction and sterically retards the additional tritylation of the C(6)-OH. Experimental Materials The α-CD was supplied by Ensuiko Sugar Refining Co., Ltd., and dried overnight in vacuo at 110 °C before use. TrCl (Tokyo Chemical

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

• 1) in acid medium does not degrade to the spiroketal but instead loses the cladinose sugar [48][49]. The degradation process terminates with decladinosyl clarithromycin in equilibrium with the 9,12-hemiacetal decladinosyl clarithromycin [50]. Unlike the acid degradation product anhydroerythromycin A

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• ] have reported the synthesis of a glycotriazolophane 309 (carbohydrate–triazole–cyclophane hybrid) from a sugar amino acid via a copper-catalyzed azide-alkyne cycloaddition sequence. An aminosugar acid was identified as a useful building block to generate cyclophanes. Thus, the treatment of 304 with

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• temperature effectively suppressed the cleavage of the sugar moiety [34] and gave the target compound 1 in high conversion. Icariside I (2) was also obtained using the same procedure from compound 13. Thus, icariin (1) and icariside I (2) were synthesized from kaempferol with 7% and 16% overall yields

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

• the anomeric position is found in the sterically favoured equatorial position located towards the β-face of the sugar ring, whereas the anomeric hydroxy group is α-positioned. Whether this particular C-type glycoside architecture is suited for FimH complexation had to be tested. Theoretical

• green) of the glycoside is pointing out of the binding site, whereas the axial 2-OH group as well as all other hydroxy groups of the sugar ring are complexed within the FimH carbohydrate binding site. Complexation of mannoside ligands is further supported by a conserved water molecule inside the

• carbohydrate binding site that is interacting mainly with the 2-OH group of the sugar ring. When the standard FimH ligand MeMan (1) is compared with the D-manno-configured C-glycosyl-type glycoconjugates 9 and 10, emerging from Amadori rearrangement of the corresponding heptopyranose 8, the axial methoxy

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• between an azido alcohol and a ketone to provide lactams through an in situ-generated hemiacetal as a temporary tether. This helps the azide addition in an intramolecular fashion, followed by ring expansion (Scheme 1) [1][2][3][4]. Recently, we applied this reaction for the synthesis of sugar–lactam

• conjugates starting from an azido-alcohol embedded in sugar derivatives and cyclic ketones [16]. In continuation of this work (and also to expand the potential of this chemistry), a new class of compounds were prepared. These cyclopentenoid–lactams, which look like carbocyclic nucleosides, were prepared

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

• their cardiovascular, antifungal, anticancer [33][34][35][36] and antithrombotic activities [37] have been investigated. Gelation ability of the pentose derivatized diosgenyl saponins have also been reported [38]. In the family of diosgenyl β-glycosides D-glucopyranose is the first sugar attached to the

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• interfaces, the surface presentation and density of the binding partners. In this work, we focus on the latter aspects. More specifically, we study the effect of linker type and ligand density on the interaction between sugar-ligands and receptors on a surface. It is well known that multivalency and linker

• looked at the interactions between the ConA receptor and its natural sugar ligand mannose. The receptor was immobilized on a glass coverslip and mannose ligands were coupled on the SCPs. Attachment of the sugar ligands on the SCP was achieved by coupling of amine-functionalized mannose to carboxy

• interface presenting the sugar ligands has a pronounced effect on the resulting adhesion energy [8]. This was shown by varying the length of poly(ethylene glycol) chains that establish the soft hydrogel matrix of the SCPs and measuring the interactions between mannose SCPs and ConA surfaces. In this work

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• 12) had marginal impact on the binding suggesting a saturation of binding site occupancy. For the structure with 6 units of maltose on each arm, a KD of 1 μM was measured which is 700-fold more potent (40-fold per sugar) than monovalent maltose. The advent of the copper-catalyzed azide–alkyne

• sugar-core glycoconjugate DNA. Combinatorial self-assembly of PNA glycoconjugates on a DNA microarray. General scheme of the 10,000 member PNA-encoded glycoconjugate library. Oligomeric interaction with arrayed mono- and divalent ligands (represented as the black spheres) as a function of surface

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• dimerized by [2 + 2] photocycloaddition. Thus, thymine functions as a control element that allows to restrict the conformational flexibility of the scaffolded sugar ligands and thus to “organize” multivalency. With this work we add a parameter to multivalency studies additional to valency. Keywords: [2 + 2

• organizing the multivalency of sugar ligands. We planned for a divalent system to start with, in which the dynamics of two at first flexible branches can be controlled by an intramolecular [2 + 2] cycloaddition reaction (Figure 1A). In order to control the [2 + 2] cycloaddition process, it was planned to

• , it is known that the thymine heterocycle can be easily N3-alkylated with, for example, bromoalkyl glycosides. This reaction can be used to install specific sugar moieties for biological recognition [5]. Hence, thymine was employed as the photosensitive control element, a functionalized mannoside was

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• ; fluorescent probes; iminosugars; 4-methylumbelliferone; multivalency; pyrene; Introduction Since the isolation in the 1970’s of 1-deoxynojirimycin (DNJ) from natural sources and the finding of its biological activity as an α-glucosidase inhibitor, thousands of sugar mimetics with a nitrogen atom replacing

• kinases [4] and cholinesterases [5], which are enzymes that act on non-sugar substrates. The versatility of iminosugars as inhibitors of enzymes of therapeutic interest has been harnessed to cure a diversity of diseases including diabetes, viral infection, lysosomal storage disorders, tumour metastasis

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• yielding than 15. The major structural difference of 14 and 15 is the first sugar attached on the resin. The N-protecting TCA group of glucosaminoside has more electron-withdrawing character in the synthesis of 15 than the benzoate ester groups of the glucoside in the synthesis of 14 which resulted in a

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010), and the “Entry

• not been elucidated in detail. Matsubara et al. introduced a sugar mimetic peptide, which binds to the sialic acid binding pocket of HA [13]. In order to increase the inhibitory capacity of the peptide, a stearyl group has been attached to the mimetic peptide, presumably leading to the formation of a

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• substituents of the sugar moiety are locked in a 1,2-cis configuration in the thiochroman ring [16][17]. With our long standing on the chemical transformation of the thiochromans into important intermediates and biologically active compounds [16][17][18][19], it was noted that hemithioacetal 3 can be readily