Chemical Synthesis of Linear and Cyclic Unnatural Oligosaccharides by Iterative Glycosidation of Ketoses

Abstract

The development of an efficient method for the stereoselective synthesis of alpha-D-(2-->1)-linked ketoside oligomers is described. The method is based on an iterative protocol composed of two key steps: a) the coupling of a thiazolylketosyl phosphite donor with an hydroxymethylketoside acceptor; and b) the introduction of the hydroxy-methyl group at the anomeric carbon atom of the resulting oligomer. To highlight its efficiency, the protocol was used in the assembly of D-galacto-2-heptulopyranose-containing oligoketosides through alpha-(2-->1) linkages up to the pentameric stage. The yield of the isolated oligomers ranged from 48 % in the first cycle to 29% in the fourth cycle. Having employed a pentenyl-substituted hydroxymethylketoside acceptor in the first cycle, all the derived oligomers contained the pentenyl group at their reducing end. This group was exploited to transform the linear oligomers into cyclic products through intramolecular glycosidation. The major product derived from the linear trisaccharide was confirmed by X-ray crystallography to be the cyclotris-(2-->1)-(alpha-D-galacto-2-heptulopyranosyl). The structure of this compound was essentially that of a [9]crown-3 ether bearing three galactopyranose rings spiroanellated in a propellerlike fashion. This arrangement of carbohydrate units linked to the crown ether created a densely alkoxylated cavity suitable for the encapsulation of alkali-metal cations (Li, Na, K, Ca, Mg).

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

“…The possibility to control not only the ring size but also the stereochemistry at the spiroketal centers by using participating (ester) or not participating (ether) protecting groups is noteworthy (Table 1). The preference for dissymmetric dispiroketal structures in the case of nonparticipating benzyl protecting groups (Scheme 4, α,β isomers) is in agreement with reported observations for other spiroketooligosaccharides [70,71]. These diastereomers can accommodate the anomeric effect at both spiroketal centres with the central 1,4-dioxane ring in a chair conformation being thermodynamically favoured.…”

A short and efficient synthesis of α-C-(1 → 3)-linked disaccharides containing deoxyhexopyranoses

“…First, the thiazole ring was converted into an aldehyde group using a known procedure. 22 Thus, compounds 10 and 11 gave the respective aldehydes 14 and 15, which were characterized by NMR spectra but, as potentially unstable compounds, they were immediately, without purification, subjected to hydroboration. Use of an excess of BH 3 AES(CH 3 ) 2 resulted in the simultaneous reduction of the aldehyde group and hydroboration of the C@C bond, which proceeded stereoselectively from the less hindered side of the dihydropyran ring.…”

Transformation of linear oligoketosides into macrocyclic neoglycoconjugates

“…Unlike the crown ether derivatives 3a-c and 4a-c, the macrocycles 7b-d and 8b-d did not serve as chiral hosts in the model Michael addition because they failed to recognize sodium and potassium cations as proved by 1 H NMR complexation experiments. 8 In conclusion, the synthetic efforts invested in this program culminated in the development of two synthetic routes leading to new classes of macrocyclic neoglycoconjugates. The use of these products as chiral receptors has been so far only scarcely investigated.…”