© 2018 Japan Society for Bioscience, Biotechnology, and Agrochemistry Trilobatin [4-(β-D-glucopyranosyloxy)-2,4”,6-trihydroxydihydrochalcone] was synthesized from commercially available naringin in three steps with an overall yield of 30%. The key step was the acid-catalyzed site-selective hydrolysis of terminal α-rhamnopyranosidic linkage in neohesperidose involved in naringin under controlled conditions, by applying a high-pressure steam sterilizer.