- Carbocyclic Substrate Analogues Reveal Kanosamine Biosynthesis Begins with the α-Anomer of Glucose 6-Phosphate
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NtdC is an NAD-dependent dehydrogenase that catalyzes the conversion of glucose 6-phosphate (G6P) to 3-oxo-glucose 6-phosphate (3oG6P), the first step in kanosamine biosynthesis in Bacillus subtilis and other closely-related bacteria. The NtdC-catalyzed r
- Vetter, Natasha D.,Jagdhane, Rajendra C.,Richter, Brett J.,Palmer, David R. J.
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p. 2205 - 2211
(2020/09/01)
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- Structure–Activity Studies of N-Butyl-1-deoxynojirimycin (NB-DNJ) Analogues: Discovery of Potent and Selective Aminocyclopentitol Inhibitors of GBA1 and GBA2
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Analogues of N-butyl-1-deoxynojirimycin (NB-DNJ) were prepared and assayed for inhibition of ceramide-specific glucosyltransferase (CGT), non-lysosomal β-glucosidase 2 (GBA2) and the lysosomal β-glucosidase 1 (GBA1). Compounds 5 a–6 f, which carry sterically demanding nitrogen substituents, and compound 13, devoid of the C3 and C5 hydroxy groups present in DNJ/NB-DGJ (N-butyldeoxygalactojirimycin) showed no inhibitory activity for CGT or GBA2. Inversion of stereochemistry at C4 of N-(n-butyl)- and N-(n-nonyl)-DGJ (compounds 24) also led to a loss of activity in these assays. The aminocyclopentitols N-(n-butyl)- (35 a), N-(n-nonyl)-4-amino-5-(hydroxymethyl)cyclopentane- (35 b), and N-(1-(pentyloxy)methyl)adamantan-1-yl)-1,2,3-triol (35 f), were found to be selective inhibitors of GBA1 and GBA2 that did not inhibit CGT (>1 mm), with the exception of 35 f, which inhibited CGT with an IC50 value of 1 mm. The N-butyl analogue 35 a was 100-fold selective for inhibiting GBA1 over GBA2 (Ki values of 32 nm and 3.3 μm for GBA1 and GBA2, respectively). The N-nonyl analogue 35 b displayed a Ki value of ?14 nm for GBA1 inhibition and a Ki of 43 nm for GBA2. The N-(1-(pentyloxy)methyl)adamantan-1-yl) derivative 35 f had Ki values of ≈16 and 14 nm for GBA1 and GBA2, respectively. The related N-bis-substituted aminocyclopentitols were found to be significantly less potent inhibitors than their mono-substituted analogues. The aminocyclopentitol scaffold should hold promise for further inhibitor development.
- Gu, Xingxian,Gupta, Vijayalaxmi,Yang, Yan,Zhu, Jin-Yi,Carlson, Erick J.,Kingsley, Carolyn,Tash, Joseph S.,Sch?nbrunn, Ernst,Hawkinson, Jon,Georg, Gunda I.
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p. 1977 - 1984
(2017/11/30)
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- Stable analogues of nojirimycin-synthesis and biological evaluation of nojiristegine and manno-nojiristegine
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Two novel iminosugars called nojiristegines, being structural hybrids between nor-tropane alkaloid calystegine and nojirimycins, have been synthesised and found to be stable molecules despite the presence of a hemiaminal functionality. The synthesised iminosugars were evaluated against a panel of glycosidases and the best inhibition (IC50), found against α-glucosidases, was in the micromolar region. The compounds were also evaluated as potential antibiotics but no useful level of activity was observed.
- Viuff, Agnete H.,Besenbacher, Louise M.,Kamori, Akiko,Jensen, Mikkel T.,Kilian, Mogens,Kato, Atsushi,Jensen, Henrik H.
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p. 9637 - 9658
(2015/09/28)
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- Iodine monochloride (ICl) as a highly efficient, green oxidant for the oxidation of alcohols to corresponding carbonyl compounds
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Iodine monochloride (ICl) was discovered to be a highly efficient, green oxidant, which can oxidize aldose hemiacetals, diarylmethanols, arylalkylmethanols, anddialkylmethanols to the corresponding aldose lactones, diarylmethanones, arylalkylmethanones, and dialkylmethanones, respectively, in high yields. ICl as a green, metal-free oxidant is characterized by mild reaction condition, short reaction time, good yield, and broad scope.
- Wei, Peng,Zhang, Datong,Gao, Zhigang,Cai, Wenqing,Xu, Weiren,Tang, Lida,Zhao, Guilong
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p. 1457 - 1470
(2015/05/20)
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- Modular stereoselective synthesis of (1→2)-C-glycosides based on the sp2-sp3 Suzuki-Miyaura reaction
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This work reports a modular and rapid approach to the stereoselective synthesis of a variety of α- and β-(1→2)-linked C-disaccharides. The key step is a Ni-catalyzed cross-coupling reaction of D-glucal pinacol boronate with alkyl halide glycoside easily prepared from commercially available D-glucal. The products of this sp2-sp3 cross-coupling reaction can be converted to glucopyranosyl, mannopyranosyl, or 2-deoxy-glucopyranosyl C-mannopyranosides by one- or two-step stereoselective oxidative-reductive transformations. To the best of our knowledge, we demonstrated the first synthetic application of a challenging sp2-sp3 Suzuki-Miyaura cross-coupling reaction in carbohydrate chemistry.
- Oroszova, Beata,Choutka, Jan,Pohl, Radek,Parkan, Kamil
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supporting information
p. 7043 - 7047
(2015/05/05)
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- α-Bromophosphonate analogs of glucose-6-phosphate are inhibitors of glucose-6-phosphatase
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Glucose-6-phosphatase (G6Pase) is an essential metabolic enzyme that has upregulated activity in Type II diabetes. Synthetic analogs of the G6Pase substrate, glucose-6-phosphate (G6P), may provide new tools to probe enzyme activity, or lead to specific inhibitors of glycosylphosphatase enzymes. Here we have developed synthetic routes to a panel of non-hydrolyzable G6P analogs containing α-bromo, α,α-dibromo, and α-bromo-α, β-unsaturated phosphonates compatible with a carbohydrate nucleus. We confirm that these functionalities have potency as inhibitors of G6Pase in vitro, providing a series of new phosphate isosteres that can be exploited for inhibitor design.
- Downey, A. Michael,Cairo, Christopher W.
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p. 123 - 132
(2013/10/22)
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- Synthesis and evaluation of eight- and four-membered iminosugar analogues as inhibitors of testicular ceramide-specific glucosyltransferase, testicular β-glucosidase 2, and other glycosidases
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Eight- and four-membered analogues of N-butyldeoxynojirimycin (NB-DNJ), a reversible male contraceptive in mice, were prepared and tested. A chiral pool approach was used for the synthesis of the target compounds. Key steps for the synthesis of the eight-membered analogues involve ring-closing metathesis and Sharpless asymmetric dihydroxylation and for the four-membered analogues Sharpless epoxidation, epoxide ring-opening (azide), and Mitsunobu reaction to form the four-membered ring. (3S,4R,5S,6R,7R)-1-Nonylazocane-3,4,5,6,7-pentaol (6) was moderately active against rat-derived ceramide-specific glucosyltransferase, and four of the other eight-membered analogues were weakly active against rat-derived β-glucosidase 2. Among the four-membered analogues, ((2R,3S,4S)-3-hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (25) displayed selective inhibitory activity against mouse-derived ceramide-specific glucosyltransferase and was about half as potent as NB-DNJ against the rat-derived enzyme. ((2S,4S)-3-Hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (27) was found to be a selective inhibitor of β-glucosidase 2, with potency similar to NB-DNJ. Additional glycosidase assays were performed to identify potential other therapeutic applications. The eight-membered iminosugars exhibited specificity for almond-derived β-glucosidase, and the 1-nonylazetidine 25 inhibited α-glucosidase (Saccharomyces cerevisiae) with an IC50 of 600 nM and β-glucosidase (almond) with an IC50 of 20 μM. Only N-nonyl derivatives were active, emphasizing the importance of a long lipophilic side chain for inhibitory activity of the analogues studied.
- Lee, Jae Chul,Francis, Subhashree,Dutta, Dinah,Gupta, Vijayalaxmi,Yang, Yan,Zhu, Jin-Yi,Tash, Joseph S.,Schoenbrunn, Ernst,Georg, Gunda I.
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p. 3082 - 3098
(2012/05/31)
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- Efficient synthesis of (6-deoxy-glycopyranosid-6-yl) sulfone derivatives and their effect on Ca2+-ATPase
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Synthesis of a series of novel (6-deoxy-glycopyranosid-6-yl) sulfone derivatives has been achieved using a general synthetic strategy. Yields were excellent in every case. The synthetic compounds were evaluated for their biological potential against Casu
- Mukherjee, Chinmoy,Ghosh, Swatilekha,Nandi, Pinki,Sen, Parimal C.,Misra, Anup Kumar
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experimental part
p. 6012 - 6019
(2011/01/13)
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- A concise synthesis of castanospermine by the use of a transannular cyclization
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(Chemical Equation Presented) A nine-step synthesis of (+)-castanospermine has been accomplished in 22% overall yield from methyl α-D- glucopyranoside. The key transformations involve a zinc-mediated fragmentation of benzyl-protected methyl 6-iodoglucopyr
- Jensen, Thomas,Mikkelsen, Mette,Lauritsen, Anne,Andresen, Thomas L.,Gotfredsen, Charlotte H.,Madsen, Robert
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scheme or table
p. 8886 - 8889
(2010/03/01)
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- Exploiting the cross-metathesis reaction in the synthesis of pseudo-oligosaccharides
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An approach to the synthesis of pseudo-oligosaccharides based on the cross-metathesis reaction between distinct sugar-olefins, followed by intramolecular cyclization of the obtained heterodimer, is presented. In particular, the relative efficiency of two
- Ronchi, Paolo,Vignando, Stefano,Guglieri, Sara,Polito, Laura,Lay, Luigi
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scheme or table
p. 2635 - 2644
(2009/10/30)
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- Do upper limits to the multiple spiro acetalization of the cyclohexane ring exist?
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An attempt to transform the pyranoside (5) into the bifaciai ligand (3) is described. The first subtarget is acetal (13) whose conversion into tris acetal (17) is made possible by remote C-H activation. Regrettably, triol (20) does not lend itself to comparable triple cyclization.
- Selvaraj, Peter R.,Paquette, Leo A.
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scheme or table
p. 165 - 168
(2009/09/08)
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- Synthesis of anti-tumour phosphatidylinositol analogues from glucose by the use of ring-closing olefin metathesis
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A divergent strategy is described for synthesis of the novel phosphatidylinositols 1-3. The synthetic approach commences from benzyl-protected methyl 6-iodo-6-deoxy-α-D-glucopyranoside, which undergoes zinc-mediated reductive fragmentation followed by vin
- Andresen, Thomas L.,Skytte, Dorthe M.,Madsen, Robert
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p. 2951 - 2957
(2007/10/03)
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- Surprising bacterial nucleotidyltransferase selectivity in the conversion of carbaglucose-1-phosphate
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The drive to understand the molecular determinants of carbohydrate binding as well as the search for more chemically and biochemically stable sugar derivatives and carbohydrate-based therapeutics has led to the synthesis of a variety of analogues that rep
- Ko, Kwang-Seuk,Zea, Corbin J.,Pohl, Nicola L.
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p. 13188 - 13189
(2007/10/03)
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- Sugar derivatives as new 6-phosphogluconate dehydrogenase inhibitors selective for the parasite Trypanosoma brucei
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Sugar derivatives mimicking compounds which take part in the catalysed reaction have been assayed as alternative substrates and/or competitive inhibitors of 6-phosphogluconate dehydrogenase from Trypanosoma brucei and sheep liver. Phosphonate analogues ha
- Pasti, Claudia,Rinaldi, Eliana,Cervellati, Carlo,Dallocchio, Franco,Hardre, Renaud,Salmon, Laurent,Hanau, Stefania
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p. 1207 - 1214
(2007/10/03)
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- Regioselective conversion of primary alcohols into iodides in unprotected methyl furanosides and pyranosides
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Two methods are described for the regioselective displacement of the primary hydroxy group in methyl glycosides with iodide. The first method is a modification of a literature procedure employing triphenylphosphine and iodine, where purification has been
- Skaanderup, Philip R.,Poulsen, Carina Storm,Hyldtoft, Lene,Jorgensen, Malene R.,Madsen, Robert
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p. 1721 - 1727
(2007/10/03)
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- Vitamin b12 catalysis of zinc-mediated 6-deoxy-6-iodopyranoside fragmentation: A mild and convenient preparation of ω-unsaturated hexose derivatives (5-hexenoses)
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The known zinc-mediated preparation of 5-hexenoses by fragmentation of 6-iodopyranosides can be performed in a simple, fast, and mild way, with less side reactions, when vitamin B12 is employed as a catalyst.
- Kleban, Martin,Kautz, Ulrich,Greul, J?rg,Hilgers, Petra,Kugler, Rolf,Dong, Han-Qing,J?ger, Volker
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p. 1027 - 1033
(2007/10/03)
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- Mirror image synthesis left ends of ciguatoxin and gambiertoxin 4b
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Three compounds related to the AB fragments of ciguatoxin and gambiertoxin 4b and two diastereomers (at the C-2 position) of the ABC fragment of ciguatoxin have been synthesized in enantiomeric form. The stereochemistry of the C-2 position was introduced selectively from the corresponding pentose derivative. Construction of the A ring with its side chain was completed by Nicholas type cyclization of an acetylene bis(cobalthexacarbonyl) complex followed by reductive decomplexation.
- Hosokawa, Seijiro,Isobe, Minoru
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- Partial synthesis of ciguatoxin (5R)-ABC segment
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An ABC segment of ciguatoxin has been synthesized in a correct enantiomeric form from a D-glucose derivative based on the route for the opposite enantiomer by switching enantiomerism of a pseudosymmetric intermediate. This route, however, has been improved in several steps and ended up with a vinylthioether group for future extension toward the D ring of ciguatoxin molecule.
- Saeeng,Isobe
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p. 1911 - 1914
(2007/10/03)
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- Nucleophilic substitutions on Multipin systems linked with a traceless linker
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The displacement of polymer-supported glucose 7 at the 6-position by azide, iodide, and acetate was achieved through a 4-hydroxybenzenesulfonate-linked Multipin system giving the corresponding glucose derivatives 8 in excellent yields. Macrocyclization of polymer-supported cyanohydrin ether 13 by displacement of the traceless sulfonate linker provided the cyclic compound 14 in moderate yield but in pure form.
- Takahashi, Takashi,Tomida, Satoshi,Inoue, Hitoshi,Doi, Takayuki
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p. 1261 - 1263
(2007/10/03)
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- Novel carbocyclic ring closure of hex-5-enopyranosides
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Retention of configuration at the anomeric carbon atom is observed for a novel rearrangement of carbohydrates. The readily accessible vinyl acetal 1 undergoes a triisobutylaluminum-assisted, stereoselective transposition of an oxygen atom on the ring with
- Das,Mallet,Sinay
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p. 493 - 496
(2007/10/03)
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- Palladium chloride mediated rearrangement of 6-deoxyhex-5-enopyranosides into cyclohexanones
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PdCl2 was found to mediate the Ferrier rearrangement of broad range of substrates catalytically in neutral conditions. In this reaction, the stereoselectivity of newly formed chiral center was controlled by the hydroxyl protective groups on the starting sugar moiety and was rationally explained by the consideration of chair like conformations.
- Iimori, Takamasa,Takahashi, Hideyo,Ikegami, Shiro
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p. 649 - 652
(2007/10/02)
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- An effective strategy for the synthesis of 6-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-D-chiro- and -D-myo-inositol 1-phosphate related to putative insulin mimetics
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Two glycosylinositol phosphates related to putative insulin mimetics, 6-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-D-chiro-inositol 1-phosphate (1) and 6-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-D-myo-inositol 1-phosphate (2), have been synthesized from selectively protected and enantiomerically pure D-chiro- and myo-inositol derivatives. The D-chiro-inositol unit was prepared in a multigram scale from D-glucose using the Ferrier's carbocyclization route, and it was transformed into the corresponding myo epimer by an oxidation-reduction sequence. The trichloroacetimidate method was applied efficiently for the key glycosylation of the inositol derivatives.
- Jaramillo,Chiara,Martin-Lomas
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p. 3135 - 3141
(2007/10/02)
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- SYNTHESIS OF CYTIDINE DIPHOSPHATE-D-QUINOVOSE
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The title molecule, cytidine-D-quinovose (CDP-6-deoxy-D-glucose) 1, was synthesized by two different methods from the key intermediate quinovose-1-phosphate 7 which was prepared from glucose.
- Liu, Li-da,Liu, Hung-wen
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- SYNTHESIS OF AMYLOSTATIN (XG), α-GLUCOSIDASE INHIBITOR WITH BASIC PSEUDOTRISACCHARIDE STRUCTURE
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The basic pseudotrisaccharide (1) constituting the common and essential building block of several α-glucosidase inhibitors of microbial origin was synthesized by coupling two synthons: the chiral cyclohexyl halide (11) and the 4'-amino-4'-deoxy-disaccharide (14).
- Sakairi, Nobuo,Kuzuhara, Hiroyoshi
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p. 5327 - 5330
(2007/10/02)
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