Alkaloids mimicking the structures of monosaccharides are now believed to be widespread in plants and microorganisms, and these sugar mimics inhibit glycosidases because of a structural resemblance to the sugar moiety of the natural substrate. Naturally occurring sugar mimics with a nitrogen in the ring are classified into five structural classes: polyhydroxylated piperidines, pyrrolidines, indolizidines, pyrrolizidines and nortropanes. Glycosidases are involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins and the lysosomal catabolism of glycoconjugates. The realization that alkaloidal sugar mimics might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes has led to increasing interest and demand for these compounds. Most of these effects can be shown to result from the direct or indirect inhibition of glycosidases. The glycosphingolipid (GSL) storage diseases are relatively rare hereditary disorders that are severe in nature and frequently fatal. Possible strategies for the treatment of these lysosomal storage diseases include enzyme replacement therapy, gene therapy and substrate deprivation. Recently, quite a new therapy for lysosomal storage diseases has been reported, namely a chemical chaperone therapy for Fabry disease. In this report, the structural basis for the specificity of inhibition of alkaloidal sugar mimics and their current and potential application to biomedical problems will be reviewed.
Cited by: | - Pearson, William H.; Guo, Luyi,""Synthesis and mannosidase inhibitory activity of 3-benzyloxymethyl analogs of swainsonine""Tetrahedron Letters2001pp. 8267-8271
Bibliographic PageFull Text - Pearson, William H.; Hembre, Erik J.,""Synthesis and mannosidase inhibitory activity of 6- and 7-substituted analogs of swainsonine""Tetrahedron Letters2001pp. 8273-8276
Bibliographic PageFull Text - Scholl, Yvonne; Hoke, Dirk; Drager, Birgit,""Calystegines in Calystegia sepium derive from the tropane alkaloid pathway""Phytochemistry2001pp. 883-889
Bibliographic PageFull Text - Chouteau, Franck; Addi, Khadija; Benechie, Michel; Prange, Thierry; Khuong-Huu, Francoise,""Stereoselective allylic transposition by means of allylic n-pentenyl ethers. Part 2: Synthesis of nitrogen heterocycles""Tetrahedron2001pp. 6229-6238
Bibliographic PageFull Text - Rambaud, Lauriane; Compain, Philippe; Martin, Olivier R.,""First total synthesis of (+)-hyacinthacine A2""Tetrahedron: Asymmetry2001pp. 1807-1809
Bibliographic PageFull Text - Scholl, Yvonne; Asano, Naoki; Drager, Birgit,""Automated multiple development thin layer chromatography for calystegines and their biosynthetic precursors""Journal of Chromatography A2001pp. 217-224
Bibliographic PageFull Text - Klitzke, Clecio Fernando; Pilli, Ronaldo Aloise,""Enhanced trans diastereoselection in the allylation of cyclic chiral N-acyliminium ions. Synthesis of hydroxylated indolizidines""Tetrahedron Letters2001pp. 5605-5608
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Bibliographic PageFull Text - Kok, Gaik B.; Campbell, Michael; Mackey, Brendan L.; von Itzstein, Mark,""Synthesis of C-3 nitrogen-containing derivatives of N-acetyl-a,b-d-mannosamine as substrates for N-acetylneuraminic acid aldolase""Carbohydrate Research2001pp. 133-139
Bibliographic PageFull Text - Enierga, Gina; Espiritu, Maria; Perlmutter, Patrick; Pham, Ngoc; Rose, Mark; Sjoberg, Stefan; Thienthong, Neeranat; Wong, Katie,""Intramolecular amidomercurations under allylic control: a stereoselective synthesis of (+)-pseudohygroline and (+)-3-hydroxypyrrolizidine""Tetrahedron: Asymmetry2001pp. 597-604
Bibliographic PageFull Text - Rothe, Grit; Garske, Uta; Drager, Birgit,""Calystegines in root cultures of Atropa belladonna respond to sucrose, not to elicitation""Plant Science2001pp. 1043-1053
Bibliographic PageFull Text - Koulocheri, Sofia D.; Magiatis, Prokopios; Skaltsounis, Alexios-Leandros; Haroutounian, Serkos A.,""Asymmetric synthesis of (2R,3S)-3-hydroxypipecolic acid d-lactam derivatives""Tetrahedron2002pp. 6665-6671
Bibliographic PageFull Text - Rothe, Grit; Drager, Birgit,""Tropane alkaloids - metabolic response to carbohydrate signal in root cultures of Atropa belladonna""Plant Science2002pp. 979-985
Bibliographic PageFull Text - Gallos, John K.; Sarli, Vassiliki C.; Stathakis, Christos I.; Koftis, Theocharis V.; Nachmia, Victoria R.; Coutouli-Argyropoulou, Evdoxia,""Hetero-Diels-Alder additions to pent-4-enofuranosides: concise synthesis of hydroxylated pyrrolizidines""Tetrahedron2002pp. 9351-9357
Bibliographic PageFull Text - Vasella, Andrea; Davies, Gideon J.; Bohm, Matthias,""Glycosidase mechanisms""Current Opinion in Chemical Biology2002pp. 619-629
Bibliographic PageFull Text - Drager, Birgit,""Analysis of tropane and related alkaloids""Journal of Chromatography A2002pp. 1-35
Bibliographic PageFull Text - Squarcia, Antonella; Vivolo, Fabrizio; Weinig, Hans-Georg; Passacantilli, Pietro; Piancatelli, Giovanni,""Glycal-mediated syntheses of enantiomerically pure polyhydroxylated g- and d-lactams""Tetrahedron Letters2002pp. 4653-4655
Bibliographic PageFull Text - Hu, X. Eric; Kim, Nick K.; Ledoussal, Benoit; Colson, Anny-Odile,""Regio- and stereo-controlled copper organometallic addition to a piperidinyl aziridine: synthesis of trans 3-amino-4-alkyl-piperidines""Tetrahedron Letters2002pp. 4289-4293
Bibliographic PageFull Text - Behr, Jean-Bernard; Guillerm, Georges,""Synthesis of 6-deoxy-homoDMDP and its C(5)-epimer: absolute stereochemistry of natural products from Hyacinthus orientalis""Tetrahedron: Asymmetry2002pp. 111-113
Bibliographic PageFull Text - Hanessian, Stephen; Bayrakdarian, Malken,""Asymmetric synthesis of diversely substituted N-hydroxypyrrolidines using cycloadditions with chiral nitrone enolate/ylids""Tetrahedron Letters2002pp. 967-971
Bibliographic PageFull Text - Cardona, Francesca; Faggi, Enrico; Liguori, Francesca; Cacciarini, Martina; Goti, Andrea,""Total syntheses of hyacinthacine A2 and 7-deoxycasuarine by cycloaddition to a carbohydrate derived nitrone""Tetrahedron Letters2003pp. 2315-2318
Bibliographic PageFull Text - Garcia, Ariel Lazaro L.; Correia, Carlos Roque D.,""Synthesis of dihydroxylated prolines and iminocyclitols from five-membered endocyclic enecarbamates. Total synthesis of the potent glycosidase inhibitor (2R,3R,4R,5R)-2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP)""Tetrahedron Letters2003pp. 1553-1557
Bibliographic PageFull Text - Behr, Jean-Bernard; Chevrier, Carine; Defoin, Albert; Tarnus, Celine; Streith, Jacques,""Asymmetric synthesis of potent glycosidase and very potent a-mannosidase inhibitors: 4-amino-4-deoxy-l-erythrose and 4-amino-4,5-dideoxy-l-ribose""Tetrahedron2003pp. 543-553
Bibliographic PageFull Text - Sha, Chin-Kang; Chau, Chi-Min,""Total syntheses of (+-)-lentiginosine and (+-)-1-epi-lentiginosine from hexahydro-1H-indol-3-one""Tetrahedron Letters2003pp. 499-501
Bibliographic PageFull Text - Scholl, Yvonne; Schneider, Bernd; Drager, Birgit,""Biosynthesis of calystegines: 15N NMR and kinetics of formation in root cultures of Calystegia sepium""Phytochemistry2003pp. 325-332
Bibliographic PageFull Text - Weintraub, Philip M.; Sabol, Jeffrey S.; Kane, John M.; Borcherding, David R.,""Recent advances in the synthesis of piperidones and piperidines""Tetrahedron2003pp. 2953-2989
Bibliographic PageFull Text - Ulgar, Victor; Lopez, Oscar; Maya, Ines; Fernandez-Bolanos, Jose G.; Bols, Mikael,""Synthesis of furan 4prime-thio-C-nucleosides, their methylsulfonium and sulfoxide derivatives. Evaluation as glycosidase inhibitors""Tetrahedron2003pp. 2801-2809
Bibliographic PageFull Text - Kim, Jin-Won; Kim, Soo-Un; Lee, Heui Sam; Kim, Iksoo; Ahn, Mi Young; Ryu, Kang Sun,""Determination of 1-deoxynojirimycin in Morus alba L. leaves by derivatization with 9-fluorenylmethyl chloroformate followed by reversed-phase high-performance liquid chromatography""Journal of Chromatography A2003pp. 93-99
Bibliographic PageFull Text - Pradera, M. Angeles; Sayago, Francisco J.; Illangua, Jose M.; Gasch, Consolacion; Fuentes, Jose,""Stereoselective synthesis of azasugar thioglycosides""Tetrahedron Letters2003pp. 6605-6608
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Bibliographic PageFull Text - Schwarz, A.; Gorniak, S.L.; Bernardi, M.M.; Dagli, M.L.Z.; Spinosa, H.S.,""Effects of Ipomoea carnea aqueous fraction intake by dams during pregnancy on the physical and neurobehavioral development of rat offspring""Neurotoxicology and Teratology2003pp. 615-626
Bibliographic PageFull Text - El-Ashry, El-Sayed H.; El Nemr, Ahmed,""Synthesis of mono- and di-hydroxylated prolines and 2-hydroxymethylpyrrolidines from non-carbohydrate precursors""Carbohydrate Research2003pp. 2265-2290
Bibliographic PageFull Text - Pino-Gonzalez, M. Soledad; Assiego, Carmen; Lopez-Herrera, F. Jorge,""Iminosugars from a,b-epoxyamides. Part 1: Synthetic approach to hydroxylated piperidine derivatives""Tetrahedron Letters2003pp. 8353-8356
Bibliographic PageFull Text - Carmona, Ana T.; Popowycz, Florence; Gerber-Lemaire, Sandrine; Rodriguez-Garcia, Eliazar; Schutz, Catherine; Vogel, Pierre; Robina, Inmaculada,""Synthesis and glycosidase inhibitory activities of 2-(aminoalkyl)pyrrolidine-3,4-diol derivatives""Bioorganic and Medicinal Chemistry2003pp. 4897-4911
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Bibliographic PageFull Text - Chevallier, Floris; Beaudet, Isabelle; Le Grognec, Erwan; Toupet, Loic; Quintard, Jean-Paul,""Allylstannation of N-acyliminium intermediates: a possible method for the stereocontrolled synthesis of polyhydroxypiperidines""Tetrahedron Letters2004pp. 761-764
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Bibliographic PageFull Text - Mechelke, Mark F.; Meyers, A. I.,""An efficient, enantioselective synthesis of branched polyhydroxylated pyrrolidines1""Tetrahedron Letters2000pp. 9377-9381
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