Xenicane Diterpenes Revisited: Thermal (E)→(Z) isomerization and conformational motions. A unifying picture

Kinetic and equilibrium studies show that typical xenicanes such as dictyolactone ( 1 ) and 4‐hydroxydictyolactone ( 3 ) undergo slow conformation medium‐ring flipping between the predominant trans ‐( 1a or 3a ; Me(20) trans to H–C(3)) and the minor cis ‐conformers ( 1b or 3b ; Me(20) cis to H–C(3); see Scheme 1 ). The formation of the latter is inhibited in heterocyclic‐ring‐opened congeners such as 18‐acetoxy‐4‐hydroxydictyo‐19‐al ( 7 ). Molecular‐mechanics calculations suggest that typical‐xenicane cis ‐conformers are disfavoured by mainly C(4)–C(5) torsional strain. This is confirmed by the observation of two sizably populated cis ‐and trans ‐conformers for the unnatural 4‐oxoxenicanes 10–12 . Unusually facile thermal ( E )→( Z ) isomerization of xenicanes 1,3,10–12 , and 7 is also observed (→ 13–17 and 9 , resp.; Scheme 3 ), reflecting great strain relief in the transition state. Conflicting results in the literature now fit into this scheme which provides a basis for unravelling recognition phenomena with these biologically active systems.