Bioinspired Total Synthesis and Structural Reidentification of Alstrostines

Area of Science:

• Natural Product Chemistry
• Synthetic Organic Chemistry
• Medicinal Chemistry

Background:

• Alstrostine A and isoalstrostine A are complex monoterpenoid indole alkaloid glycosides from Apocynaceae and Rubiaceae plants.
• Their large size, multiple chiral centers, and fused structures make structural elucidation via spectral analysis extremely challenging.
• Total synthesis is crucial for definitive structural identification and understanding these natural products.

Purpose of the Study:

• To achieve the first asymmetric total syntheses of alstrostine A and isoalstrostine A.
• To confirm and revise the proposed stereochemistry of alstrostine A.
• To develop a synthetic strategy applicable to related complex alkaloids.

Main Methods:

• Development of an 18- or 19-step asymmetric total synthesis.
• Utilized a key two- or three-component coupling reaction between secologanin and a pyrrolidinoindoline moiety.
• Synthesized all isomers of the pyrrolidinoindoline fragment to explore stereochemical possibilities.

Main Results:

• Successful completion of the first asymmetric total syntheses of alstrostine A and isoalstrostine A.
• The synthetic approach allowed for the revision of the stereochemistry of alstrostine A.
• A previously identified compound was re-identified as epialstrostine A, a new stereoisomer.

Conclusions:

• The total synthesis provides unambiguous structural confirmation of alstrostine A and isoalstrostine A.
• The study revises the stereochemistry of alstrostine A and introduces epialstrostine A.
• The developed synthetic strategy is valuable for accessing complex indole alkaloid glycosides.