Chemoenzymatic total synthesis of sorbicillactone A

Area of Science:

• Natural product chemistry
• Synthetic organic chemistry
• Biotechnology

Background:

• Sorbicillinoids are a diverse class of natural products with significant biological activities.
• Sorbicillactone A, a unique nitrogen-containing sorbicillinoid, displays potent anti-leukemic and anti-HIV effects.
• Its complex structure necessitates efficient synthetic strategies for further investigation.

Purpose of the Study:

• To develop a chemoenzymatic synthesis for sorbicillactone A and its analogs.
• To enable detailed biological and structure-activity relationship studies.
• To explore the biosynthetic pathway of sorbicillactone A.

Main Methods:

• Enzymatic enantioselective oxidative dearomatization of sorbillin to sorbicillinol using SorbC.
• Stereoselective Michael addition of a fumarylazlactone building block.
• Chemoenzymatic synthesis strategy for efficient analog generation.

Main Results:

• Successful synthesis of sorbicillactone A and several analogs with high yields.
• Precise stereochemical control achieved throughout the synthesis.
• Identification of key enzymatic and chemical steps for a convergent route.

Conclusions:

• A novel, efficient, and stereoselective chemoenzymatic route to sorbicillactone A and analogs has been established.
• The developed method facilitates in-depth biological studies of this promising natural product.
• Findings suggest an analogous biosynthetic pathway for sorbicillactone A.