Andrzej Frankowski

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.

New stereocontrolled transformations in the imidazolosugar series

The isomeric imidazolopyrrolidinose 1, imidazolopiperidinose 2 and imidazoloazepanose 3, potential glycosidase inhibitors, were obtained in several steps from d-glucose.

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.

Photochemical synthesis of diaza-steroids

Abstract N-Iminopyridinium ylides 12 and 13 readily undergo regio-specific photoinduced ring expansion to the isomeric 1,2-diazepines 14 and 15 respectively. Similarly UV irradiation of the steroidal N-iminopyridinium ylide 25, which can be obtained from 19-nortestosterone, leads quantitatively and in a regiospecific manner to the corresponding diazepine 26. In a second photochemical reaction 26 gives the cyclobutene derivative 27. Variable temperature 1H NMR and OCD measurements of the optically active diazepine 26 indicate that one of the two possible diastereoisomeric conformations is preferred.

Photochemical transformations of 3,3,4,7-tetramethylpyrazolo[3,4-d]pyridazine in solution and frozen gas matrices

Photochemical transformations of pyrazolopyridazine 1 give isopropenylpyridazine 2 in addition to cyclopropapyridazine 3 in solution and to the ring-opened diazo isomer 4 observed in frozen gas matrices.