Improved Synthesis for Modular Ascarosides Uncovers Biological Activity.

Area of Science:

• Organic Chemistry
• Chemical Synthesis
• Molecular Biology

Background:

• Ascarosides are crucial signaling molecules in nematodes, regulating development and behavior.
• Understanding ascaroside structure and function is key to controlling nematode populations.

Purpose of the Study:

• To develop a versatile synthetic route for modular ascarosides.
• To enable the selective introduction of diverse side chains onto the ascaroside scaffold.
• To investigate the biological activity of synthetic ascarosides.

Main Methods:

• Synthesis of a cyclic sulfate intermediate from methyl-α-l-rhamnopyranoside.
• Hydrogenolysis of the cyclic sulfate to yield modular ascarosides.
• Selective functionalization at the 1, 2, and 4 positions of the sugar moiety.
• Bioassays using synthetic ascarosides, including 4'-tigloyl ascaroside mbas#3.

Main Results:

• A versatile and efficient synthesis of modular ascarosides was achieved.
• The method allows for the regioselective introduction of various side chains.
• Synthetic ascarosides from *C. elegans* and *P. pacificus* were successfully prepared.
• 4'-Tigloyl ascaroside mbas#3 was identified as an avoidance or dispersal signal.

Conclusions:

• The reported synthetic strategy provides access to a wide range of ascaroside analogs.
• This work facilitates further research into ascaroside-mediated signaling in nematodes.
• The identification of specific signaling roles for ascarosides opens avenues for targeted interventions.