Zoe E. Wilson

Molecules derived from the extremes of life

In order to survive extremes of pH, temperature, salinity and pressure, organisms have been found to develop unique defences against their environment, leading to the biosynthesis of novel molecules ranging from simple osmolytes and lipids to complex secondary metabolites. This review highlights novel molecules isolated from microorganisms that either tolerate or favour extreme growth conditions.

Isolation, biological activity and synthesis of benzannulated spiroketal natural products.

Covering: up to late 2009 A review of the isolation, biological activity and synthesis of natural products containing a benzannulated spiroketal moiety is provided.

A flexible asymmetric synthesis of the tetracyclic core of berkelic acid using a Horner–Wadsworth–Emmons/oxa-Michael cascade

The one-pot Horner-Wadsworth-Emmons/oxa-Michael cascade followed by spiroketalisation affords the tetracyclic benzannulated spiroketal core of berkelic acid, an extremophile natural product with selective activity against ovarian cancer.

An enantioselective formal synthesis of berkelic acid.

An enantioselective formal synthesis of berkelic acid is described. The key step involves a late-stage silyl enol ether addition to a benzannulated oxonium ion with subsequent spiroketalization leading to construction of the tetracyclic core. Thermodynamically controlled equilibration under acidic conditions affords the desired spiroketal configuration as a single diastereoisomer.

Formal Synthesis of Berkelic Acid: A Lesson in α-Alkylation Chemistry

The full details of our enantioselective formal synthesis of the biologically active natural product berkelic acid are described. The insertion of the C-18 methyl group proved challenging, with three different approaches investigated to install the correct stereochemistry. Our initial Horner-Wadsworth-Emmons/oxa-Michael approach to the berkelic acid core proved unsuccessful upon translation to the natural product itself. However, addition of a silyl enol ether to an oxonium ion, followed by a one-pot debenzylation/spiroketalisation/thermodynamic equilibration procedure, afforded the tetracyclic structure of the berkelic acid core as a single diastereoisomer.

Synthetic approaches to [5,6]‑benzannulated spiroketal natural products

Studies toward the synthesis of three biologically active [5,6]-benzannulated spiroketal natural products are described. The first total synthesis of paecilospirone is reported, employing a late-stage, pH-neutral spiroketalization. A formal synthesis of γ-rubromycin is described, where the spiroketal moiety is formed by delicate manipulation of the electronic properties of the spirocyclization precursor. Finally, model work toward the total synthesis of berkelic acid is summarized, introducing a novel Horner–Wadsworth–Emmons/oxa-Michael (HWE/oxa-M) cascade to access the spiroketal precursor.