A Synthesis of (±)-Aplydactone.

Area of Science:

• Marine Natural Products Chemistry
• Organic Synthesis
• Photochemistry

Background:

• Aplydactone is a unique brominated sesquiterpenoid isolated from the sea hare Aplysia dactylomela.
• Its structure is characterized by a highly strained skeleton with fused four- and six-membered rings and three contiguous quaternary carbons.
• Previous attempts to synthesize aplydactone, particularly from chamigrane precursors, have been unsuccessful, hindering further investigation into its properties and origin.

Purpose of the Study:

• To achieve the first total synthesis of aplydactone.
• To explore novel synthetic strategies for constructing strained polycyclic systems.
• To develop efficient methods for installing sterically hindered functional groups, such as the secondary bromide.

Main Methods:

• The synthesis employed two key photochemical steps to construct the challenging cyclobutane rings.
• An unconventional Barbier-type cyclization was utilized to form a crucial C-C bond.
• New radical conditions were developed to introduce the sterically hindered secondary bromide moiety.

Main Results:

• Aplydactone was successfully synthesized, confirming its complex structure.
• The developed photochemical strategy proved effective in assembling the strained bicyclic core.
• The novel radical conditions enabled the installation of the sterically demanding secondary bromide.

Conclusions:

• The total synthesis of aplydactone was accomplished using innovative, non-biomimetic photochemical and radical methodologies.
• This work provides a viable route to aplydactone and related compounds, facilitating further biological and chemical studies.
• The synthetic strategies developed can be applied to the construction of other complex natural products with strained ring systems.