Trifluoroacetyl‐Containing Scaffolds Assisted in Total Synthesis of Oxostephanine and Thailandine and Their Antimicrobial Activity

Abstract

AbstractThis study is the first to fully synthesize oxostephanine (1) and thailandine (2), two aporphine alkaloids that were originally found in Stephania venosa (Blume) Spreng. The synthesis described in this study utilized commercially available starting materials, namely 2‐bromo‐6‐methoxybenzaldehyde and 3,4‐dihydroxybenzaldehyde. The B‐ring moiety of aporphines was successfully synthesized through the utilization of the Bischler‐Napieralski cyclization process. The synthesis of the C ring in oxoaporphine was accomplished using an order of crucial steps, namely biaryl coupling, incorporation of trifluoroacetyl‐containing scaffolds, and palladium coupling, followed by oxidation using Fremy's salt. The synthesis of oxostephanine (1) and thailandine (2) was successfully achieved in 11 and 12 steps, respectively, resulting in equivalent overall yields of 11.7 %. This study aimed to increase amount of interested compounds and explore the biological activity of those compounds. In this study, both compounds were subjected to testing for antibacterial activity using the CLSI standard M100 guideline. Oxostephanine (1) has shown significant antibacterial efficacy against gram‐positive bacteria and bacterial biofilms, as seen by minimum inhibitory concentration (MIC) values ranging from 7.8 to 125 μg/mL. Conversely, higher MIC values of 250 μg/mL indicated that thailandine (2) exhibited limited antimicrobial activity.