The Synthesis of Imidazol Sugars Which Mimic Cyclic Carboxonium Ions Formed During the Glycosidase‐Catalysed Hydrolysis of Oligo and Polysaccharides

Abstract

Some naturally occurring carbohydrates, of which several hydroxy groups had been selectively protected, were condensed with formamidine to give the expected imidazole derivatives in the D‐arabino (9), D‐lyxo (12), L‐xylo (17), D‐threo (21), and in the L‐ and D‐erythro (24) series. Introduction of a strong leaving group at the remaining free alcohol function of these products led at once to intramolecular SN2 cyclisation to the corresponding bicyclic aza sugar derivatives. This was followed by total deprotection to give the target aza sugars in the L‐xylo (7), L‐ribo (14), D‐arabino (19), as well as in the D‐threo (22) and the L‐ and D‐erythro (26) series. Inhibitory assays with four glycosidases showed that the D‐arabino aza sugar 19 is the only potent inhibitor (for an α‐mannosidase of jack bean).

Stereomeric Pyrrolidinopentoses Bearing an Imidazole Ring − Synthesis, Chiroptical Properties, and Evaluation as Potential Sugar-Mimic Glycosidase Inhibitors

“…[11] Retrosynthetic analysis of its enantiomer ent-2 (Scheme 2) required the -threo derivative 6 Ϫ a compound that we had prepared previously [12] Ϫ as the chiral starting material and an imidazol-4-yl anion, the preparation of which had been described and discussed in detail elsewhere. [13Ϫ15] Suffice it to say that a solution of EtMgBr in diethyl ether had to be added to 4-iodo-1-tritylimidazole in dry CH 2 Cl 2 to give the C(4)-metallated imidazole building block, which was not isolated.…”

“…After the standard workup, -xylo derivative 16 was isolated and partly deprotected by fluoride ion (TBAF/THF) to give 17, which was debenzylated by catalytic hydrogenolysis to yield the desired -xylo target molecule 3. The synthesis of the -xylo enantiomer ent-3 had already been described previously [8,11] and its 3D structure demonstrated by single-crystal X-ray diffraction analysis. [8] The 1 H and 13 C NMR spectra of 3 proved to be identical to, and therefore superimposable on, those of ent-3.…”

“…The synthesis of the -ribo enantiomer ent-5 had already been described by us in a previous publication. [11] The 1 H and 13 C NMR spectra of 5 and ent-5 proved to be identical and superimposable. Furthermore, their chiroptical properties permitted their 3D mirror image relationship to be demonstrated unambiguously (Table 1 and Figure 1).…”

“…[11] Here we describe the detailed syntheses of the five remaining stereomers (Scheme 1). 1 H and 13 C NMR spectra, as well as CD spectra corroborated the expected absolute configurations for all eight stereomers.…”

Cyclic amidines as precursors for imidazoles

“…2-Hydroxy-aldehydes (sugars) also react in like fashion with formamidine acetate, to produce 4(5)-substituted imidazoles. 6,7 Scheme 1. General reaction of an amidine with a 2-halo-ketone.…”