SYNTHESIS AND REACTIONS OF 1-[1-OXIDO-2-(3,4)-PYRIDINYL]-2-METHYLOXIRANES WITH NITROGEN NUCLEOPHILES

Reaction of 2(3,4)-pyridinecarboxaldehydes (5) with ethylidenetriphenylphosphorane afford a mixture of stereoisomers Z-(6) and E-1-[2(3,4)-pyridinyl]-1-propenes (7). m-Chloroperbenzoic acid oxidation of 6 and 7 yields a 60:40 mixture of Z-(8) and E-1-[1-oxido-2(3,4)-pyridinyl]-2-methyloxiranes (9). The regiospecific reaction of Z-isomers 8a-c with cyclic amines as piperidine give rise to threo-1-hydroxy-1-[1-oxido-2(3,4)-pyridinyl]-2-(1-piperidino)propanes (10) while the E-isomer 9a yields erythro-11. The E-isomers 9b and 9c having 1-oxido-3(4)-pyridinyl substituents afford erythro-12 resulting from attack by piperidine at C-1 of the oxirane. Reductive deoxygenation using 10% Pd on charcoal and hydrogen gas effectively removed the N-oxide substituent from the threo-10 and erythro-11 .beta.-aminoalcohols. Dilute solution IR spectroscopy indicated the existence of strong intramolecular hydrogen bonding in the .beta.-aminoalcohols 10 and 11. The assignment of relative configuration of diastereoisomers 10 and 11 was based on the magnitude of the vicinal coupling constant J where J threo is greater than J erythro. [There has recently been a considerable degree of pharmacological interest in arylsulfonylhydrazones of 2-formylpyridine N-oxide (1) and methenomycins (2) as antineoplastic agents. The synthesis of 2- and 4-oxiranylpyridine 1-oxides and their reaction with N, O and S nucleophiles has been described. The related oxiranes 8 and 9 for evaluation should be studied as antitumor agents.].