On the influence of unsaturation on the macrolactonization of hydroxy fatty acids.

Regioselectivity and yields of Yamaguchi cyclization of (15S,16S)-15,16-dihydroxy-otadecyl-(6Z,9Z,12Z)-trienoic acid and its saturated homologue have been compared at different temperatures and concentrations. For the unsaturated species the regioselectivity of cyclization depends on temperature to such an extent that the preferred regioisomer changes as the temperature changes, whereas for the saturated homologue the even-membered ring turns out to be always the preferred one. Molecular mechanics is used to interpret these findings. For both dihydroxyacids, there is experimental evidence that the yields of the two monocyclic regioisomers are thermodynamically controlled, unlike those of the analogue monohydroxy lactones. The higher cyclization yield of the unsaturated monohydroxyacid is interpreted in terms of conformational pre-organization. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]