Explorations of Caffeic Acid Derivatives: Total Syntheses of Rufescenolide, Yunnaneic Acids C and D, and Studies toward Yunnaneic Acids A and B

Yunnaneic
acids A–D, isolated from the roots of Salvia
yunnanensis, are hexameric (A and B) and trimeric
(C and D) assemblies of caffeic acid that feature an array of synthetically
challenging and structurally interesting domains. In addition to being
caffeic acid oligomers, yunnaneic acids A and B are formally dimeric
and heterodimeric adducts of yunnaneic acids C and D. Herein we report
the first total syntheses of yunnaneic acids C and D featuring the
formation of their bicyclo[2.2.2]­octene cores in a single step from
simple precursors via an oxidative dearomatization/Diels–Alder
cascade that may have biogenetic relevance. In addition, exploitation
of the key intermediate resulting from this cascade reaction has enabled
rapid access to the structurally related caffeic acid metabolite rufescenolide
through an unexpected Lewis acid-mediated reduction. Finally, we report
the results of extensive model studies toward forming the dimeric
yunnaneic acids A and B. These explorations indicate that the innate
reactivities of the monomeric fragments do not favor spontaneous formation
of the desired dimeric linkages. Consequently, enzymatic involvement
may be required for the biosynthesis of these more complex family
members.