As this dehydrative cyclization process is extremely
facile (particularly under acidic conditions), it has fre-
quently been speculated that it occurs nonenzymatically
in the biosynthetic pathways of many spiroketal natural
products. Nonetheless, either the cyclohexene units or
spiroketal moieties that reside in natural molecules typically
present defined stereochemical configurations,
leading to the hypothesis that the associated biosynthetic
transformations are enzyme directed.