A general strategy for the synthesis of aignopsanes, a new family of sesquiterpene natural products of marine origin, is presented. The total synthesis of (+)‐aignopsanoic acid A (1), (−)‐methyl aignopsanoate A (2), and (−)‐isoaignopsanoic A (3) has been achieved and their absolute configuration confirmed. (+)‐Microcionin‐1 (4), a structurally related furanosesquiterpene isolated in both enantiomeric forms from marine sponges, was also synthesized and its absolute configuration established in an unambiguous way. Interestingly, we report that (+)‐microcionin‐1 (4), can be converted by a simple oxidation process to aignopsanoic acid A (1). This transformation supports the hypothesis that (+)‐microcionin‐1 (4) may be an intermediate in the biosynthesis of aignopsanes.