Chemical and Enzymatic Approaches to Carbohydrate-Derived Spiroketals: Di-D-Fructose Dianhydrides (DFAs)

Abstract

Di-d-fructose dianhydrides (DFAs) comprise a unique family of stereoisomeric spiro-tricyclic disaccharides formed upon thermal and/or acidic activation of sucrose- and/or d-fructose-rich materials. The recent discovery of the presence of DFAs in food products and their remarkable nutritional features has attracted considerable interest from the food industry. DFAs behave as low-caloric sweeteners and have proven to exert beneficial prebiotic nutritional functions, favouring the growth of Bifidobacterium spp. In the era of functional foods, investigation of the beneficial properties of DFAs has become an important issue. However, the complexity of the DFA mixtures formed during caramelization or roasting of carbohydrates by traditional procedures (up to 14 diastereomeric spiroketal cores) makes evaluation of their individual properties a difficult challenge. Great effort has gone into the development of efficient procedures to obtain DFAs in pure form at laboratory and industrial scale. This paper is devoted to review the recent advances in the stereoselective synthesis of DFAs by means of chemical and enzymatic approaches, their scope, limitations, and complementarities.

Structural and Functional Basis for Substrate Specificity and Catalysis of Levan Fructotransferase

“…1A) (8,9,12). Because DFAs produced by these enzymes have various beneficial effects on human health and as such are used as dietary supplements and low calorie sweeteners, DFA production has gained the attention of food microbiologists and biotechnologists (13,14).…”

Stereoselective Synthesis of Difructose Dianhydrides by Use of the Xylylene Group as Stereodirecting Element in Spiroketalisation Reactions

“…The latter structure is actually the thermodynamically most stable DFA. [1,2,7] The fact that the difuranose compound is preferentially obtained even in this case underlines the importance of kinetic considerations when designing stereoselective syntheses of spiroketal derivatives (Table 2). Catalytic hydrogenolysis of 33-35 (with prior deacetylation in the case of 34) afforded the fully unprotected DFA 3 (Scheme 5).…”

“…3.84 (dd, J 6a,6b = 11.5, J 5,6a = 2.0 Hz, 2 H, 6a-H), 3.73 derivatives or their mixtures was effected by catalytic hydrogenolysis with Pd/C (10 %) at 1 atm in EtOAc/MeOH (1:1) containing formic acid (10 %). The identities and relative proportions of diastereomers in the reaction mixtures were determined by GC, by comparison with authentic standards, [1,2,7] after transformation into the corresponding mixtures of fully unprotected DFAs and further derivatisation as the corresponding hexa-O-trimethylsilyl derivatives, according to the previously reported protocol. [12,14] Supporting Information (see footnote on the first page of this article):…”

“…[1,2] Their identification as the major components of the thermolysis products of sucrose-and d-fructose-containing food materials, such as caramel or chicory, [3][4][5][6] together with their promising prebiotic properties, have strongly stimulated research into their preparation and nutritional properties. [7][8][9][10][11] Recently, a methodology for the preparation of DFA-enriched caramels based on the use of acid ion-exchange resins as caramelisation promoters has been reported.…”

Synthesis of β-D-Fructopyranosyl-(2→6)-D-glucopyranose from D-Glucose and D-Fructose by a Thermal Treatment

“…We could find no report of a disaccharide synthesized from the two kinds of saccharide, D-fructose and D-glucose, excepting di-D-fructose dianhydrides from fructose, sucrose, levan or inulin by a thermal treatment. 12,13) …”