Synthesis of progesterone heterocyclic derivatives of potential antimicrobial activity

The aim of this work was to synthesize steroidal heterocycles and to elucidate the potential role of these compounds as antimicrobial agents. The synthesis of steroidal heterocycles containing the pyrazole, isoxazole, thiazole, pyrane, pyridine, pyridazine, or benzopyrane ring attached to the pregnene nucleus is reported. Progesterone (1) reacts with dimethyl formamide dimethyl acetal to form enamine 2. Heterocyclization of 2 with hydrazines, hydroxylamine, glycine, ethyl acetoacetate or cyanomethylene afforded novel steroidal heterocyclic derivatives. The in vitro antimicrobial evaluation showed that all synthesized compounds show activity against the used strains of Gram positive bacteria and fungi. U radu je opisana sinteza steroidnih heterocikličkih spojeva i evaluacija njihovog antimikrobnog djelovanja. Sintetizirani spojevi sadrže pirazol, izoksazol, tiazol, piran, piridin, piridazin ili benzopiran na pregnenskoj jezgri. Progesteron (1) je prvo u reakciji s dimetil formamid dimetil acetalom dao enamin 2. Novi steroidni heterociklički derivati dobiveni su heterociklizacijom spoja 2 s hidrazinima, hidroksilaminom, glicinom, etilacetoaceatom i cijanometilenom. Antimikrobno vrednovanje in vitro pokazalo je da su svi sintetizirani spojevi aktivni protiv testiranih Gram pozitivnih bakterija i gljivica.