Biomimetic Total Synthesis of Bisorbicillinol, Bisorbibutenolide, Trichodimerol, and Designed Analogues of the Bisorbicillinoids

Abstract

The bisorbicillinoids are a growing class of novel natural products endowed with unique biological activity and are associated with fascinating hypotheses for their biosynthesis. A full account of our biomimetic explorations toward the bisorbicillinoids including the total syntheses of bisorbicillinol (1), bisorbibutenolide (2), and trichodimerol (4) from sorbicillin (3) is disclosed. Utilizing the novel dimerization reactions discovered and fine-tuned en route to 1 and 4, several analogues of these natural products have been synthesized. Furthermore, studies on the scope of these novel cycloaddition reactions and the isolation of a number of unexpected products along with proposed mechanisms for their formation are reported. These findings add to our knowledge of the largely unexplored chemistry of o-quinols and related aromatic systems.

Novel Sorbicillin Derivatives with an Unprecedented Carbon Skeleton from the Sponge‐Derived Fungus Trichoderma Species

“…Diels-Alder cycloaddition, as in the case of bisorbicillinol, [22] and Michael addition, as suggested for trichodimerol. [23] Compounds 1-4, even though sharing the basic sorbicillin part of their structures with that of other sorbicillinoids, possess an unprecedented tricyclic ring system. They are unique with regard to ring C, which may arise biosynthetically by combining a non-sorbicillinoid polyketide with the hexaketide-derived sorbicillinol.…”

Sequential Reactions Initiated by Oxidative Dearomatization. Biomimicry or Artifact?

“…In a more recent related example, Antus has shown that oxidative dimerization of isoeugenol (5) leads to dehydrodiisoeugenol (9) in a single operation (Scheme 20.3) [8]. Treatment of 5 with phenyl iodine diacetate (PIDA) results in the formation of p-phenoxonium 6, the resonance structure (7) of which is intercepted by a second equivalent of isoeugenol (5).…”

Fungal Metabolites, Sorbicillinoid Polyketides and Their Effects on the Activation of Peroxisome Proliferator-activated Receptor γ

“…Compound 2 was obtained as an amorphous yellow powder and was shown to possess a molecular formula of C 28 H 34 O 8 by positive HRFABMS. The 1 H and 13 C NMR spectra of compound 2 displayed the characteristic paired signals including those of trichodimerol (1), suggesting that compound 2 is a modified trichodimerol (1) and is based on a bisorbicillinoid skeleton [16,21]. (1) is partially saturated.…”