PROGRESS TOWARDS NEW SYNTHESES IN CARBOHYDRATE CHEMISTRY

Amélia Pilar Rauter

Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, 5º Piso, 1749-016 Lisboa, Portugal.
E-mail: aprauter@fc.ul.pt; Tel: +351 217500952; Fax: +351 217500088


Keywords: C-C, C-O, C-S, C-N bond formation; sugar lactones; keto sugars; deoxy sugars; acid zeolites.

Strategies leading to C-C bond formation and to the stereoselective synthesis of a variety of biomolecules starting from sugars will be presented. Approaches for the synthesis of lactones possessing insecticidal and fungicidal activities will be presented, either based on the stereoselective transformation of a sugar epoxide with phenyl selenoacetic acid or phenyl selenopropionic acid, followed by oxidation, or based on a Reformatsky-type reaction of a keto sugar or a sugar lactone with ethyl bromomethylacrylate and activated zinc. Wittig reaction of 3-keto sugars with [(ethoxycarbonyl)methylene]triphenylphosphorane proved to be a key step for the stereoselective synthesis of the sugar moieties of amipurimycin, miharamycin and analogues. These natural antibiotics are highly efficient against the rice blast disease caused by Pyricularia oryzae, which is considered an agricultural bioterrorism agent.
Synthetic pathways using dialdofuranoses and sugar nitriles as synthons for the preparation of bioactive pseudo-C-nucleosides will be presented. These approaches led to the preparation of compounds with thiazole, thiazolidinone, triazole, tetrazole, and pyrazole rings bonded to C-4 of the furanose moiety, some of which responsible for neuroactivity in insects.
Keto sugars are common starting materials for a variety of transformations, being easily obtained by oxidation with pyridinium chlorochromate. The efficiency of this reagent for the oxidation of primary and secondary alcohols in various positions of furanose and pyranose derivatives will be demonstrated, as well as its use for a direct synthesis of macrocyclic bislactones, starting from protected glucose derivatives which possess positions 2,3 or 3,4 free.
Direct conversion of an a-hydroxy keto sugar, an a-hydroxy sugar ester, lactone or amide into the corresponding a-deoxy keto sugar, a-deoxy sugar ester, lactone or nitrile will be reported using the system triphenylphosphine/iodine/imidazole. This procedure is very convenient when compared to most of the deoxygenation methods described in the literature, which involve usually two or more steps.
An efficient and straightforward method for the C-O, C-S, and C-N bond formation based on the reaction of glycals with a variety of glycosyl acceptors (aliphatic alcohols, sterols, flavonoids, sugars, thiols, heterocyclic bases) catalysed by triphenylphosphine hydrobromide will be discussed.
Acid zeolites proved to be very useful for synthetic purposes in carbohydrate chemistry, namely for the preparation of isopropylidene derivatives, for the oxidation of the benzyl group to give the benzoyl group, for the synthesis of Ferrier products and also for the stereoselective formation of b-furanosides.