SYNTHETIC STUDY OF HEPOXILINS .3. SYNTHESIS, PROPERTIES, AND IDENTIFICATION OF EPIMERIC HEPOXILINS (-)-(10R)-B3 AND (+)-(10S)-B3

To characterize the individual epimers of hepoxilin B3, a new total synthesis procedure was developed consisting of subsequent condensations of enantiomerically pure (2R,3S)-epoxy-5-undecynal with LiC=CCH2Cl and HC=C(CH2)3COOMe, followed by Lindlar hydrogenation, and finally epimer separation. Derivatives of hepoxilin syn-(10R,11R,12S)-B3 (free acid, methyl ester and acetate of methyl ester) are more polar on silica gel, have negative optical rotations [a]25D-60.6-degrees, -62.6-degrees, -25.2-degrees, respectively, and in H-1 NMR spectra have the larger splitting of carbinolic H-10 signal (J10,11 5.0-6.1 Hz). Corresponding values for less polar hepoxilin anti-(10S,11R,12S)-B3 derivatives are: [a]25D +73.5-degrees, +61.9-degrees, and -2.0-degrees; J10-11 2.95-3.3 Hz. These data suggest that an epimer of hepoxilin B3 recently isolated by W.H.Gerwick et al. from red algae is syn-(10R,11R,12S)-B3.