title: Total synthesis of 17-isoLevuglandin E4 and the structure of C22-PGF4alpha.
abstract: The isolevuglandin 17-isoLGE4 (10-acetyl-11-formyl-14-hydroxynonadeca-4(Z),7(Z),12(E),16(Z)-tetr aenoic acid) is a levulinaldehyde derivative that is expected to be generated during the free radical-induced oxidation of docosahexaenoic acid. A total synthesis was executed to facilitate detection and identification of 17-isoLGE4 in biological samples. Conjugate addition of a higher order vinyl cyanocuprate to a gamma-alkoxy enone achieved the final carbon-carbon bond formation to complete a convergent elaboration of the 17-isoLGE4 carbon skeleton. Attempted construction of the requisite vinyl nucleophile synthon using hydrostannylation of an alkyne was foiled by tri-n-butylstannyl radical-promoted isomerization of a cis to a trans double bond. Derivatization of 17-isoLGE4 with methoxylamine under anhydrous or wet conditions generated bismethoximes of 17-isoLGE4 or the isomerized delta11-17-isoLGE4 respectively. Analysis of the mass spectrum of a bismethoxime-pentafluorobenzyl ester-trimethylsilyl ether derivative of 17-isoLGE4 provided presumptive evidence that an incorrect structure was proposed earlier for C22-PGF4alpha, the only F4-isoprostane which is produced enzymatically. We conclude that the 22-carbon analogue of PGF2alpha, produced from docosahexaenoic acid by a cyclooxygenase from trout gill, does not have the same side chains as 17-isoLGE4. Furthermore, we now propose that mass spectral data reported for "C22-PGF4alpha" support a 14-PGF4alpha structure rather than the 17-PGF4alpha structure suggested previously.
authors.affiliation: Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA.
authors.forename: W
authors.initials: W
authors.lastname: Sha
authors.forename: R G
authors.initials: RG
authors.lastname: Salomon
mesh_terms: D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011458:Prostaglandins E / Q000138:chemical synthesis* / Q000737:chemistry; D011460:Prostaglandins F / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry; D017971:Tin Compounds / Q000737:chemistry
chemical_list: C414099:17-isolevuglandin E4; D011458:Prostaglandins E; D011460:Prostaglandins F; D012503:Saponins; D017971:Tin Compounds; C031525:stannane; C034239:C22-prostaglandin F4alpha