Bioinspired Semisynthesis and Structure Revisions of Chlorinated Norsesquiterpenoids Rumphellatins A-C.

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Chlorine-containing hemiketals, specifically rumphellatins, are complex norsesquiterpenoids with potential biological activity.
• Previous synthetic routes to these compounds were limited, hindering further investigation.

Purpose of the Study:

• To develop the first total synthesis of rumphellatins A-C.
• To revise and confirm the structures of these natural products.
• To provide access to these compounds for biological profiling and biosynthetic studies.

Main Methods:

• Total synthesis starting from commercially available (-)-β-caryophyllene oxide.
• Structural elucidation and confirmation using spectroscopic methods.
• Chemical transformations to access target hemiketals.

Main Results:

• Successful synthesis of rumphellatins A-C (1-3) was achieved.
• Structures of rumphellatins A (1) and C (3) were revised.
• Structures of rumphellatin B (2) and intermediate rumphellolide C (19) were confirmed.

Conclusions:

• The study provides a viable synthetic route to previously inaccessible chlorine-containing hemiketals.
• The availability of these norsesquiterpenoids facilitates their biological activity profiling.
• This research aids in understanding the biosynthetic pathways of rumphellatins.