10.1021/jo981929t.s001
Subhas C. Roy
Subhas C.
Roy
Laxmi Nagarajan
Laxmi
Nagarajan
Robert G. Salomon
Robert G.
Salomon
Total Synthesis of Iso[7]-Levuglandin D<sub>2</sub>
American Chemical Society
1999
multifunctional vinyl cyanocuprate
arachidonic acid
heptadecadienoic
acetyl
Iso
conjugate addition
Total Synthesis
group manipulations
iso
1999-01-23 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Total_Synthesis_of_Iso_7_-Levuglandin_D_sub_2_sub_/3716334
Iso[7]-levuglandin D<sub>2</sub> (iso[7]-LGD<sub>2</sub>, 9-acetyl-8-formyl-5-hydroxy-6(<i>E</i>),11(<i>Z</i>)-heptadecadienoic acid)
is a structural isomer of levuglandin D<sub>2</sub> (9-acetyl-8-formyl-12-hydroxy-5(<i>Z</i>),10(<i>E</i>)-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]-LGD<sub>2</sub> was devised. The functionality in iso[7]-LGD<sub>2</sub> 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]-LGD<sub>2</sub> lactone and the free acid.