Reversible deprotonation of fascaplysin ( 1 ) was achieved with non‐nucleophilic bases (Scheme 1). Under basic aqueous conditions, opening of ring D of 1 occurred, yielding zwitter‐ionic reticulatine 2a , whereas, in a methoxide‐containing MeOH solution, an unexpected addition of three molecules of MeOH to the pyridinium ring produced an isomer mixture 3 of a trimethoxy‐substituted compound (Scheme 2). Transformation of the keto group of 1 to the oxime 4A took place in the presence of pyridine as base (Scheme 3). Grignard and alkyllithium reagents added as expected to the keto group of 1 , providing tertiary alcohols 5 and 6 (Scheme 4).