jo981929t_si_001.pdf (466.18 kB)
Total Synthesis of Iso[7]-Levuglandin D2
journal contribution
posted on 1999-01-23, 00:00 authored by Subhas C. Roy, Laxmi Nagarajan, Robert G. SalomonIso[7]-levuglandin D2 (iso[7]-LGD2, 9-acetyl-8-formyl-5-hydroxy-6(E),11(Z)-heptadecadienoic acid)
is a structural isomer of levuglandin D2 (9-acetyl-8-formyl-12-hydroxy-5(Z),10(E)-heptadecadienoic
acid) that we postulate to be generated during nonenzymatic free radical-induced oxidation of
arachidonic acid. To facilitate detection and identification in biological samples, a total synthesis
of iso[7]-LGD2 was devised. The functionality in iso[7]-LGD2 is diverse and chemically sensitive,
and an acid-catalyzed lactonization of the allylically activated δ-hydroxy acid array present in the
synthetic target was encountered that occurs readily in aqueous solution. Nevertheless, conjugate
addition of a multifunctional vinyl cyanocuprate to achieve the final carbon−carbon bond-forming
step, followed by a sequence of functional and protecting group manipulations, reproducibly delivered
a readily separable 3:7 mixture of iso[7]-LGD2 lactone and the free acid.