Structural Revision of a Natural Tetrahydroquinoxaline-6-carboxylic Acid Isolated from <i>Caulis Sinomenii</i> through Total Synthesis of Both the Regioisomers

Here we disclose the total synthesis of two regioisomeric ribose-linked 1,2,3,4-tetrahydroquinoxaline-6-carboxylic acids (<b>1</b>) for the first time. This effort helped to reassign the originally proposed structure of a natural product isolated from a Chinese medicinal plant, <i>Caulis Sinomenii,</i> and correct the biological activity reported in the patent. The use of commercially available methyl 4-fluoro-2-methyl-5-nitrobenzoate as a starting material to access both regioisomers, installation of the amino-sugar moiety, and construction of the quinoxalinedione ring using diethyl oxalate are the key highlights. In addition, we showed that readily available riboflavin can also be converted to the natural product (revised structure). Evaluation of the antibacterial activity of both target compounds showed no activity (up to 512 μg/mL) under the test conditions employed in this study.