A rapid and efficient access to renieramycin-type alkaloids featuring a temperature-dependent stereoselective...

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Renieramycin-type alkaloids are a class of natural products with demonstrated antitumor activity.
• Developing efficient synthetic routes to these complex molecules is crucial for further biological evaluation and drug development.
• Existing synthetic methods may lack practicality or flexibility for accessing diverse analogs.

Purpose of the Study:

• To develop a flexible and practical asymmetric synthesis protocol for renieramycin-type antitumor alkaloids.
• To establish a rapid construction of the common pentacyclic framework.
• To synthesize representative members, (-)-renieramycin G and (-)-jorunnamycin A.

Main Methods:

• Employing a stereoselective Pictet-Spengler cyclization of key intermediates (amino ester 16 and aldehyde 15) by temperature regulation.
• Utilizing automatic lactamization following N-deprotection of the cyclization product.
• A 19-step synthesis starting from L-tyrosine.

Main Results:

• Successfully constructed the common pentacyclic framework of renieramycin-type alkaloids.
• Achieved the synthesis of (-)-renieramycin G with a 15.8% overall yield.
• Synthesized (-)-jorunnamycin A with a 14.3% overall yield.

Conclusions:

• The developed protocol offers a flexible and practical approach for the asymmetric synthesis of renieramycin-type antitumor alkaloids.
• The strategy enables rapid access to the core pentacyclic structure.
• This work provides a valuable synthetic route for obtaining important antitumor natural products and their analogs.