Dariusz Deredas

Stereoisomeric Imidazolo-Pentoses − Synthesis, Chiroptical Properties, and Evaluation as Glycosidase Inhibitors

The syntheses of all four imidazolo-piperidino-pentoses in the L-series ent-2 to ent-5, and of three out of the four possible stereomers in the D-series 3, 4, and 5, are reported. The linear imidazolo sugar precursors were prepared, either by double condensation of formamidine with protected aldohexoses, or by nucleophilic addition of a lithiated imidazole derivative to protected aldotetroses. Cyclisation of these linear imidazolo-carbohydrates was performed by intramolecular SN2 reactions. These were followed by deprotection to the target molecules. The four pairs of opposite enantiomers showed pronounced mirror-image-type Cotton effects in their CD spectra. All stereomers of the D-series show a negative rotatory power ([α]D), while the stereomers of the L-series show a positive one. None of the eight imidazolo sugars inhibited the replication of HIV-1. Some of them proved to be rather selective but only moderately potent inhibitors of α-glycosidases, as determined by Michaelis-Menten kinetics.

SYNTHESIS OF AN IMIDAZOLO-L-LYXO-PIPERIDINOSE DERIVATIVE

Abstract Imidazolo-L-lyxo-piperidinose 4 was synthesised from the D-galactose derivative 8 by two reaction sequences, via removal of a terminal carbon atom, stepwise incorporation of an imidazole moiety, and eventually intramolecular SN2 reaction to the corresponding piperidine ring. Piperidinose 4 proved to be a poor glycosidase inhibitor.

Stereocontrolled synthesis of imidazolo[1,5]hexopiperidinoses and imidazol-4(5)-yl-C-glycosides

Abstract The syntheses of imidazolo[1,5]hexopiperidinoses 2–6 and imidazol-4(5)-yl C-glycosides 7–9 are reported. The crucial step of this approach relies upon the SN2-type cyclisation of selectively protected C(1), C(2), C(3) and C(5)-substituted 1-[imidazol-4(5)-yl]pentitols in which the imidazole nitrogen or the C(1)-connected oxygen are involved as the competitive nucleophilic centers, respectively. Six selected imidazolosugars were evaluated as potential inhibitors of glycosidases.

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

The syntheses of the imidazolo-pyrrolidino-pentoses ent-2 (L-arabino), 3 (D-xylo), 4 (D-lyxo), ent-4 (L-lyxo), and 5 (D-ribo) are reported, completing the series of all eight possible stereomers. The corresponding five linear imidazolo sugar precursors were prepared by nucleophilic addition of C(4)-metallated imidazole derivatives to the appropriately configured and protected aldotetroses. Cyclisation of the resulting linear imidazolo-carbohydrates was performed by means of intramolecular Walden inversion processes, followed by deprotection to afford the five target imidazolo-sugars. Three of the four D-configured stereomers proved to be good to moderate glycosidase inhibitors, as determined by Michaelis−Menten kinetics.

Three-component reaction of 3-(diethoxyphosphoryl)coumarin, enolizable ketones and primary amines: Simple, stereoselective synthesis of benzo[1,3]oxazocine skeletons

The synthesis of benzoxazocine phosphonates was accomplished by means of the three-component reaction of 3-(diethoxyphosphoryl)coumarin, enolizable ketones and benzylamine. An asymmetric version of this reaction was also developed. Treatment of the coumarin with cyclopentanone and (R)- or (S)-1-phenylethylamine afforded enantiomerically pure benzoxazocine phosphonates in a 2.5:1 diastereoisomeric ratio. In contrast, similar reaction with cyclohexanone provided α-phosphono-δ-enamides as single diastereoisomers. The mechanistic features of the reaction were discussed. A transition state model rationalizing its stereochemical outcome was proposed. The α-phosphono-δ-lactams obtained were transformed into the corresponding α-methylene-δ-lactams. The cytotoxicity of these compounds was evaluated.