Renieramycins M (1m) and N (1n) were isolated from the Thai sponge Xestospongia sp., pretreated with potassium cyanide in methanolic buffer solution, and their structures and relative stereochemistries were elucidated on the basis of spectroscopic data. This strategy is the first example of the gram-scale preparation of this series of compounds and presents a potential solution for increasing the gram-scale supply of novel natural products from marine sources.