Synthetic approaches towards cortistatins: evolution and progress through its ages

Area of Science:

• Organic chemistry
• Medicinal chemistry
• Pharmacology

Background:

• Cortistatins are steroidal alkaloids with a unique pentacyclic structure.
• They exhibit potent anti-angiogenic activities, crucial for cancer therapy.
• Natural scarcity necessitates synthetic approaches.

Purpose of the Study:

• To provide an exhaustive review of synthetic strategies for cortistatins.
• To highlight the structure-activity relationships (SAR) of cortistatin analogues.
• To discuss the challenges and advancements in synthesizing these complex molecules.

Main Methods:

• Review of published total synthesis efforts for cortistatins A and J.
• Analysis of synthetic routes for other cortistatin family members.
• Compilation of structure-activity relationship data from designed analogues.

Main Results:

• Successful total syntheses of key cortistatin congeners achieved.
• Development of various analogues with modified biological activities.
• Gained insights into SAR, guiding future drug design.

Conclusions:

• Synthetic chemistry has overcome challenges in accessing cortistatins.
• Understanding SAR is crucial for developing novel anti-angiogenic agents.
• Further research can lead to new therapeutic strategies targeting angiogenesis.