Total synthesis of (+/-)-hasubanonine

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• Alkaloids, such as hasubanonine, are a significant class of natural products with diverse biological activities.
• The total synthesis of complex alkaloids presents a considerable challenge in organic chemistry.

Purpose of the Study:

• To describe a novel and efficient total synthesis of the alkaloid (+/-)-hasubanonine.
• To showcase a synthetic route featuring key transformations for constructing the hasubanonine core structure.

Main Methods:

• The synthesis involved generating a phenanthrene intermediate through a sequence of Suzuki coupling, Wittig olefination, and ring-closing metathesis.
• Subsequent conversion to the target molecule included dearomatization via oxidative phenolic coupling, anionic oxy-Cope rearrangement, and acid-promoted cyclization.

Main Results:

• A total synthesis of (+/-)-hasubanonine was successfully completed.
• The study identified and suppressed the formation of an undesired rearranged product in the final cyclization step by optimizing acid strength.

Conclusions:

• The developed synthetic route provides an effective strategy for accessing hasubanonine and related alkaloids.
• Optimization of reaction conditions, particularly acid moderation, is crucial for controlling product distribution in complex cyclizations.