Total synthesis of iso[7]-levuglandin D-2

Iso[7]-levuglandin D-2 (iso[7]-LGD(2), 9-acetyl-8-formyl-5-hydroxy-6(E), 11 (Z)-heptadecadienoic acid) is a structural isomer of levuglandin D-2 (9-ace tyl-8-formyl-12-hydroxy-5(Z), 10(E)-heptadecadienoic acid) that we postulat e-to be generated during nonenzymatic free radical-induced oxidation of ara chidonic acid. To facilitate detection and identification in biological sam ples, a total synthesis of iso[7]-LGD(2) was devised. The functionality in iso[7]-LGD(2) is diverse and chemically sensitive, and an acid-catalyzed la ctonization of the allylically activated delta-hydroxy acid array present i n the synthetic target was encountered that occurs readily in aqueous solut ion. Nevertheless, conjugate addition of a multifunctional vinyl cyanocupra te to achieve the final carbon-carbon bond-forming step, followed by a sequ ence of functional and protecting group manipulations, reproducibly deliver ed a readily separable 3:7 mixture of iso[7]-LGD(2) lactone and the free ac id.