3,5-Disubstituted isoxazoles as synthons for (±)-pyrenophorin and (±)-vermiculine synthesis.

A new approach to suitably protected forms 21,29, and 30 of the monomeric units 3 and 4, which correspond to the dimeric macrolide antibiotics (*)-pyrenophorin (1) and (A)-vermiculine (2), involved ethyl 3-(3-butenyl)- 5-isoxazolecarboxylate (6) as common starting material. The partial structure composed of an cqo-unsaturated acid with an oxygen function at the y-position, featured in both the natural compounds, was efficiently created by reductive fission of the N-0 bond of the isoxazole nucleus bearing a 5-carboxylate, which contains it in a latent form, followed by suitable operations. The terminal double bond of 6 allowed us to introduce the missing functions, namely, a hydroxyl group for 3 and a P-hydroxy ketone moiety for 4. A Markovnikov hydration to give 8 and regiospecific cycloaddition of acetonitrile oxide followed by reductive opening of the formed isoxazoline 22 secured the appropriate functional groups for 3 and 4, respectively.