1778 Papers SYNTHESIS Abstract: Two approaches for the chain elongation and synthesis of 6-deoxyheptose derivatives are described. The first one is based on the regioselective ring opening of 4,6-cyclic sulfate glycopyra- noside derivatives at carbon 6 by cyanide ion. The second approach involves the ring expansion of 5,6-anhydro to 5,7-anhy- dro sugars and subsequent opening of the resulting oxetane deriv- ative using acetate ion as nucleophile. Key words: chain elongation, 6-deoxyheptoses, cyclic sulfate, oxetanes, oxiranes Naturally occurring 6-deoxyheptoses have been found as constituents of bacterial polysaccharides 1 although little is known about their biosynthesis and biological role. Most of the reported synthetic approaches are based on chain extension at the C-6 position of hexoses, e.g. via a nitrile, a Wittig reaction, dithioacetals and organometallic re- agents, among others. 1 Cyclic sulfates of mono- saccharides 2,3 or 5,6-anhydroaldose 4–6 derivatives have been used in some of those approaches as precursors of 6- deoxyheptoses. In this paper we wish to report further on the applications of these two classes of compounds in the synthesis of 6-deoxyheptose derivatives. The use of cyclic sulfates as an active form of diols to- wards nucleophilic attack provides an efficient and versa- tile method in synthesis. 7–9 We have investigated the reac- tivity of cyclic sulfates of sugars and discovered some in- Synthesis of 6-Deoxyheptose Derivatives via Cyclic Sulfates and Oxetanes Antonio Vargas-Berenguel, a * Francisco Santoyo-González, b * José A. Calvo-Asín, b Francisco G. Calvo-Flores, b Juan M. Expósito-López, a Fernando Hernández-Mateo, b Joaquín Isac-García, b Juan J. Giménez Martínez a a Área de Química Orgánica, Universidad de Almería, 04120 Almería, Spain Fax: +34(950)215481; E-mail: avargas@ualm.es b Instituto de Biotecnología, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain Fax: +34(958)243186; E-mail: fsantoyo@goliat.ugr.es Received 29 May 1998 teresting applications in the synthesis of episulfide and olefin derivatives, thiosugars 10,11 and, as well, thio-linked disaccharides. 12 On the other hand, it is known that ox- iranes undergo ring expansion when treated with dimeth- ylsulfoxonium methylide affording oxetanes. 13,14 Since oxetanes are latent 1,3-diols, we can envisage a new meth- od for the chain elongation at C-6 of hexoses, and hence, for the synthesis of 6-deoxyheptoses, from 5,6-anhydro- hexofuranose derivatives. Cyclic sulfates of sugars with D-gluco, D-manno and D- galacto configuration 1–6 were prepared in good to high yields (Table 1) from the corresponding diols following a synthetic route described earlier for 3 and 6 11,12 which was based on the procedure by Gao and Sharpless. 15 The reac- tion of compounds 1–6 with lithium or sodium cyanide was performed in DMF at room temperature for 4– 40 hours giving rise to the lithium or sodium sulfate deriv- atives 7–12 in good yields (Table 2, entries 1–7). As ex- pected, the nucleophilic ring opening of the 4,6-cyclic sul- fates 1–5 occurred regioselectively at the less sterically hindered 6-position and the reaction conditions were com- patible with ester protection of the hydroxyl groups at C- 2,3. However, the reaction of the less reactive 3,4-cyclic sulfate 6 with lithium or sodium cyanide failed to give the corresponding nitrile derivative and instead, the 2,3-anhy-