Leccinine A (1) along with a known compound (2), were isolated from the edible mushroom Leccinum extremiorientale. The structure of 1 was determined by the interpretation of spectral data. Leccinine A showed protective activity against endoplasmic reticulum stress-dependent cell death. Seven analogues (3e9) of 1 were synthesized in order to evaluate the structureeactivity relationship, and the result indicated that the formamide group of 1 was indispensable for the activity.