On the Origin of Dolabriferol: Total Synthesis via Its Putative Contiguous Precursor

Area of Science:

• Organic Synthesis
• Natural Product Chemistry
• Chemical Artifacts

Background:

• Dolabriferol is a natural product whose biosynthetic origin remains unclear.
• Previous hypotheses suggested a polypropionate pathway for dolabriferol formation.
• Understanding the origin of natural products is crucial for synthetic and biosynthetic studies.

Purpose of the Study:

• To synthesize the proposed polypropionate precursor of dolabriferol.
• To experimentally investigate the proposed retro-Claisen fragmentation pathway for dolabriferol formation.
• To determine if dolabriferol could be an artifact of isolation or purification.

Main Methods:

• Enantioselective aldol coupling with kinetic resolution was employed to synthesize the polypropionate precursor.
• A racemic C1-C8 ketone fragment and an enantiopure C9-C15 aldehyde fragment were used in the key coupling step.
• The synthesized precursor was treated with alumina to induce fragmentation.

Main Results:

• The polypropionate precursor was successfully synthesized via enantioselective aldol coupling.
• Treatment of the precursor with alumina resulted in clean transformation to dolabriferol.
• The transformation occurred via a regioselective retro-Claisen fragmentation.

Conclusions:

• The synthesis provides the first experimental evidence supporting the proposed polypropionate origin of dolabriferol.
• The results demonstrate that dolabriferol is a plausible isolation artifact, potentially formed during sample processing.
• This study offers insights into the chemical reactivity and potential artifactual formation of natural products.