Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• by acid catalysis from renewable resources, such as sugars, lignocellulosic biomass and waste materials [18]. It can be used as a bifunctional precursor for the synthesis of pharmaceuticals, plasticizers, and different additives [19]. Furthermore, it is recognized as an excellent starting material

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• loads has led to mechanoenzymatic transformations [5][6][7], and to synthesize amino acid derivatives [8][9][10] and peptides [11][12][13] by ball milling and extrusion techniques. Similarly, mechanochemical derivatizations of sugars and sugar derivatives such as cyclodextrins (CDs) have proven

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• vary with Leishmania species (>20 species) and life stage of the pathogen, making it challenging to define how the capping sugars interact and modulate host immune responses [21][22][23][24]. Since these cell-surface glycans are structurally diverse and difficult to isolate in appreciable quantities

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• can be ligated through the inverse electron-demand Diels–Alder (DAinv) reaction with 1,2,4,5-tetrazines [13][14][15][16][17]. This reaction is advantageous since it is fast, irreversible, and does not require a toxic heavy metal catalyst. Different terminal alkenes that are connected to sugars by an

• of the deacetylated (water-soluble) sugars, the performance of the sugars in MGE, and the assessment of their metabolic acceptance. The studies uncovered that Ac4ManNCp is much better accepted than Ac4ManNCyoc although their membrane staining intensity after MGE is comparable. The high metabolic

• linkage has a higher impact on the reaction rate than the removal of the methyl group; k2 of ManNCyoc is eleven times higher than that of ManNCp. In conclusion, the three cyclopropene-modified sugars rank in the order ManNCyc, ManNCp, and ManNCyoc with the latter being the fastest. Metabolic

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• aromatic and aliphatic substrates to peptides, steroids, sugars, etc.) [26], but also from the different MCRs used. Although the Ugi 4CR is the most commonly used transformation in this context, interesting examples exploiting other MCRs have been reported (Scheme 6) [27][28]. However, when the first MCR

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• adopted to access NR+ and NMN. 2.1. Glycosylation of nicotinamide As mentioned above, glycosylation of Nam may be performed either by using halosugars, i.e., 2,3,5-tri-O-acyl-D-ribofuranosyl halides, or by applying 1,2,3,5-tetra-O-acyl-D-ribofuranoses. The latter fully acylated sugars require different

• riboside anomers were synthesized, with the best β/α-anomer stereoselectivity obtained when the chloride form of the sugars were used as precursors. Thus, the reaction between Nam (1a) and 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride (3a) in acetonitrile at 0 °C yielded the triacetylated product 4a mainly

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• . Changes in the synthetic stage sequence led to variable layer compositions. Various linear and star-shaped (triarm) ABA and ABCBA amphiphilic multiblock copolymers containing acetal-protected sugars (APS) were prepared by the coupling of an end-functionalized ROMP copolymer of norbornene (NB) and APS

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

• improving the already existing protocol [50]. The sugars 2α/β were then individually treated with the Ruppert–Prakash reagent (TMSCF3) as difluorocarbene precursor and sodium iodide as initiator [52], furnishing the exo-tricyclic sugars 3α/β as major isomers. The closer evaluation of this reaction revealed

• to the hindrance of the difluorocarbene attack on the double bond. The stereochemistry around the cyclopropane ring (endo vs exo) could be assessed by the characteristic coupling pattern between the fluorine atom and the H-C(1) or C(7) in the endo-tricyclic sugars in the corresponding 1H and 13C NMR

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• structures 3-amino-2-deoxy sugars [1]. For instance, N,N-dimethyl-L-vancosamine is an essential component of pluramycin antibiotics such as kidamycin and pluramycin A via a C-glycosidic linkage (Figure 1). For constructing aryl C-glycoside bonds, glycal derivatives are versatile synthetic intermediates

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• were as potent as spinetoram, a few of the analogues have only a 20–40 times lower activity than spinetoram. In particular, one of these analogues was approximately as active as spinosad. This study highlights the possibility of developing new insecticidal chemistries by replacing sugars on natural

• of spinosyns via chemical modification [18]. Bioactivities of many microbial secondary metabolites are highly dependent on their sugar constituents which are transferred as nucleotide-activated sugars to an aglycon by glycosyltransferases [19]. Therefore, bioactivities of these metabolites could

• groups. It also highlights the potential for developing new insecticidal products by replacing sugars on natural products with other groups. Experimental Insecticide bioassays The insecticidal activities of spinetoram J analogues were evaluated against third-instar larvae of P. xylostella. Stock

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

• group participation in conformer 9b leads to the same anomer as predicted by the Fürst–Plattner rule. Neighboring group participation provides an alternative explanation for the already mentioned longer reaction times for the acylated sugars 7j–m. Because of the high delocalization of the positive

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• the current conjugation approach, we then turned our attention to the use of relatively longer peptides, sugars, and lipids as biomolecules (Table 2) [76][77]. When pentapeptide 6 was used instead (see Scheme S4 in Supporting Information File 1 for preparation of pentapeptide 6), however, the

• phosphodiester bond can be an effective linkage not only to construct oligonucleotides but also to conjugate them to various biomolecules, including peptides, sugars, and lipids. The development of a method to activate the supported 5’-terminus, affording useful stable phosphoramidites that are compatible with

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

• glycosciences. Therefore, this review focuses on the use of the Mitsunobu reaction for modifications of sugar hemiacetals. Strikingly, unprotected sugars can often be converted regioselectively at the anomeric center, whereas in other cases, the other hydroxy groups in reducing sugars have to be protected to

• applications of the Mitsunobu reaction in glycochemistry have mostly dealt with the functionalization of the primary hydroxy group of sugars and, to a lesser extent, with modifications of the secondary alcohol array in carbohydrate rings [2][3][4][5][6], for example for halogenation [20]. However, the

• Mitsunobu reaction can also be profitably utilized for the anomeric modification of carbohydrates. Hence, we have focused this review on the utilization of the Mitsunobu reaction for manipulations of the carbohydrate hemiacetal, where reducing (anomerically unprotected) sugars react as the alcohol component

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

• 2,3-di-O-isopropylidene group. Before our reports regarding the Pummerer-type glycosylation, the synthesis of 4’-thionucleosides was based on the known chemistry: typically, a 1-acetoxy-4-thiosugar or its synthetic equivalent was obtained from natural sugars and subjected to the Vorbrüggen reaction as

• viewpoint of the synthetic method, the reaction would be useful for dehomologation of aldoses and preparation of chiral synthons deriving from sugars. The reaction procedure involves the initial formation of an alkoxy anomeric radical by a hypervalent iodine reagent in the presence of iodine, which triggers

• latter reaction was employed to synthesize dihydropyranonucleosides. Oxidative scission is a characteristic reaction mediated by hypervalent iodine reagents and is typically used for dehomologation of sugars. A one-pot glycosylation using this reaction was also developed for the synthesis of acyclic

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

• relationship studies. Several strategies for the synthesis of 2-amino sugars have been published so far. In one exemplary straightforward approach, GalNAc was prepared by inverting the stereogenic center at the C-4 position of N-acetylglucosamine (GlcNAc) [10]. However, the necessity of using a 2-amino sugar

• the missing isomers of 2-amino sugars, as well as new derivatives are still highly desired. The here presented flexible approach towards GalNAc and IdoNAc from epoxythreitol 5 is a first step to answer this request. These molecules can be approached from tartaric acid (3), which already provides two

• peracetylated to yield compounds 8a and 8b. The azide function was reduced with H2 and Pd/C in acetic anhydride to gain the fully acetylated amino sugars 2a and 2b. In the final step, the compounds were deprotected using a mixture of MeOH/H2O/Et3N to yield D-GalNAc (1a) and L-GalNAc (1b). As proof of concept

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

• . The overarching features of these compounds with regards to changes in the nucleobase and sugars allow optimal interactions with enzymes resulting in potent and often times, selective, inhibitory activities [18][65][74][96]. As continuing efforts to design greater diversity in C-nucleosides, methods

• in terms of increasing diversity and reducing the time and length of the syntheses [70][71][72][73][76]. Efforts have been aided by advances in the synthesis of modified sugars and sugar mimics, particularly D-ribonolactone analogues [53][73][75][97]. Furthermore, chemical and theoretical studies

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• Jayashree Rajput Srinivas Hotha Madhuri Vangala Department of Chemistry, Indian Institute of Science Education and Research, Pune 411 008, India 10.3762/bjoc.14.56 Abstract Herein we report, for the first time, the successful anomeric azidation of per-O-acetylated and per-O-benzoylated sugars by

• catalytic amounts of oxophilic AuBr3 in good to excellent yields. The method is applicable to a wide range of easily accessible per-O-acetylated and per-O-benzoylated sugars. While reaction with per-O-acetylated and per-O-benzoylated monosaccharides was complete within 1–3 h at room temperature, the per-O

• -benzoylated disaccharides needed 2–3 h of heating at 55 °C. Keywords: acylated sugars; azidation; gold(III) bromide; N-glycoside; oxophilicity; Introduction The past few decades had seen the enrichment of transition metal complexes in various glycosylation strategies [1]. In particular, gold complexes with

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• macrocycle with sucrose scaffold. The proposed methodology allows for the regioselective introduction of various polyhydroxylated unsaturated fragments (derived from different sugars) at either terminal position of sucrose which undergo an efficient cyclization under the RCM conditions. Although, for

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• ; oligosaccharides; Review Introduction Glycosyl oxazolines are high-energy intermediates on the hydrolytic pathway of some [1][2][3][4][5] (but not all) [6] of the numerous glycosidases that hydrolyse linkages between 2-acetamido sugars and other species. In particular the endo-β-N-acetylglucosaminidases [7

• intermediate [8]. Glycosyl oxazolines first drew the attention of synthetic chemists due to their use as glycosyl donors for the synthesis of oligosaccharides that comprise 2-amino-2-dexoy sugars [9]. Though the majority of synthetic work focussed on production and reaction of gluco-configured oxazolines (i.e

• sugars as substrates presents some limitations, as any remaining protecting groups must be removed in a subsequent step. Firstly, and most importantly, glycosyl oxazolines are extremely labile to acidic hydrolysis, and so this approach precludes the use of any OH-protecting groups that require acidic

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• ., (almost) exclusively L-amino acids and D-sugars are found. Among other properties, chiral chromophoric molecules absorb left circularly polarized light (L-CP light) differently from right circularly polarized light (R-CP light). L-CP and R-CP light can be seen as the two components, rotating in opposite

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• chain β-hydroxy fatty acids, anomeric phosphorylation and the synthesis of binary glycosyl phosphodiesters involving two amino sugars. Explicit structure–activity relationships data obtained with synthetic lipid A derivatives would also help to design novel therapeutic approaches for sepsis and

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• aggregation thus served as the basis for the analyte detection. The functionalization of AuNPs with carbohydrates using AAC The functionalization of AuNPs with carbohydrates using CuAAC Although several groups have used the CuAAC to attach thiol-containing ligands to various sugars and then subsequently

• attach these sugar-containing thiol ligands to AuNPs [70][71][72][73], there has so far only been one study that reported the use of the CuAAC to click sugars directly onto the surface of AuNPs. In 2008, Chikae et al. reported the use of CuAAC to react alkyne-terminated thiol-functionalized AuNPs that

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

• glycosides constitute a very important group among spirostanol saponins. Diosgenin has a double bond between the C-5 and C-6 atoms of the spirostanol skeleton and can be found in combination with different sugars in Costus, Discorea, Paris, Solanum, Yucca, and Trillium plants [11]. The plants containing

• by a quartet of the carbonyl carbon (≈157 ppm) with the JC,F coupling constant ≈39 Hz and a quartet of the CF3 carbon (≈117 ppm) with the JC,F coupling constant ≈290 Hz (see Supporting Information File 1 for experimental and NMR data). Strategies for the preparation of ureido sugars usually involve

• Supporting Information File 1 for experimental and NMR data). To obtain the N-alkyl derivatives of 4, a method called “two-step reductive alkylation of amines” was chosen. This method was successfully used to prepare N-alkyl derivatives of other amino sugars, including diosgenyl aminoglucosides [34][35]. The

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• ongoing research to increase the selectivity of antitumor active metal complexes [17][18][19][20][21][22], our focus was on the synthesis of curcuminoids that could serve as building blocks to attach sugars like D-fructose or D-glucose [23]. Due to the easy accessibility to azido sugars [24][25] we

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

• : higher carbon sugars; reductive amination; sucrose; Introduction Carbohydrates, because of their availability in a variety of optical pure forms, are particularly useful in planning and executing the synthesis of chiral macrocyclic compounds [1][2][3][4][5]. In this context, polyhydroxylated derivatives

• with long chains are very interesting. However, the synthesis of this kind of molecules is a real challenge in carbohydrate chemistry. Very often reactions, which work well for ‘normal’ (C5–C7) sugars are not applicable for the elongated analogs [6][7]. Recently we have prepared such a derivative by

• , including cyclic ones. We decided to perform a model study on the efficient differentiation of the terminal positions in such higher sugars or alditols, which could open a route to complex polyhydroxylated derivatives. Results and Discussion A regioselective protection of one of the primary hydroxy groups