SYNTHETIC STUDIES OF FLUORINATED ANALOGS OF 1-AZAFAGOMINE - REMARKABLE NUCLEOPHILIC-SUBSTITUTION OF FLUORINE BY HYDRAZINE

luoro-4-hydroxy-3-hydroxymethylhexahydropyridazine (7) and some other azafagomine analogues were synthesised with the aim of comparing their glycosidase inhibition to that of )-4,5-dihydroxy-3-hydroxymethylhexa hydropyridazine (1-azafagomine). Both in the synthesis of 7 and in the attempted synthesis of 4,5-dihydroxy-3-fluoromethylhexahydropyridazin e, a remarkable degree of nucleophilic substitution of fluorine by hyd razine was observed in the final deprotection step involving hydrazino lysis. Fluorine analogue 7 was a considerably weaker glycosidase inhib itor than I, suggesting that the 3-OH of 1 play a role in its binding by acting as a hydrogen bond donator. (C) 1997 Elsevier Science Ltd.