Synthetic Access to Morpholine and Oxazolidine Derivatives as Next-Generation Antifungal Scaffolds

Ravsaheb Kalyankar, Savita Desai (Dhongade)

Abstract: Antifungal agents are therapeutic compounds that selectively target fungal pathogens with minimal toxicity to the host, leveraging biochemical differences between mammalian and fungal cells. Allylamines such as naftifine and terbinafine, along with the morpholine-based drug amorolfine, inhibit ergosterol biosynthesis by acting on squalene epoxidase. Inspired by this mechanism, novel morpholine and oxazolidine scaffolds were explored for their synthetic potential and antifungal relevance. Scaffold-I was synthesized in 96 % yield via a self-catalyzing condensation of bromo benzoate with morpholine in DMF, circumventing the limitations of conventional Buchwald reactions that require palladium catalysts and pose challenges in catalyst removal. Morpholin-3-one and oxazolidin-2-one was prepared by condensing 2-aminoethanol with chloro acetyl chloride and by reacting epichlorohydrin with potassium isocyanate, respectively. These intermediates were further condensed with halo benzoates using K?CO?, NaI, and ethylenediamine in dry dioxane to yield Scaffolds II and III. Structural confirmation of the synthesized scaffolds was achieved through spectral analysis. These scaffolds are intended to be conjugated with selected linkers to develop antifungal agents with enhanced efficacy, broad administration routes, and minimal side effects. Their biological activity will be evaluated in comparison with amorolfine to assess their potential as next-generation antifungal therapeutics.

Keywords: Morpholine, Oxazolidine, Antifungal agents, Ergosterol biosynthesis, Scaffold synthesis, Spectral analysis

How to Cite?: Ravsaheb Kalyankar, Savita Desai (Dhongade), "Synthetic Access to Morpholine and Oxazolidine Derivatives as Next-Generation Antifungal Scaffolds", Volume 14 Issue 11, November 2025, International Journal of Science and Research (IJSR), Pages: 1591-1595, https://www.ijsr.net/getabstract.php?paperid=SR251122121602, DOI: https://dx.doi.org/10.21275/SR251122121602