Tryptanthrin (tryp) is being studied as a lead compound with pharmacological activity that is found in nature. To date, synthetic and pharmacological studies on trypanthrin have focused on substitution patterns on the A and D rings, while structural modifications of the A ring system have yet to be explored synthetically. In this study, we synthesized a tryp derivative containing a five-membered heterocyclic ring (thiazole and thiophene) on ring A using solid-phase synthesis. In the synthesis, two-site oxidation of sulfide and benzylic positions using an oxidant was successfully performed. A total of 53 derivatives were synthesized, and the yield per step in six steps was 46-96%. In addition, it was observed that oxidizing agents such as FeCl₃ and H₅IO₆ caused oxidation of the Merrifield resin, leading to damage of the resin. This study demonstrates the feasibility of introducing diverse five-membered heterocycles into natural product frameworks.