Orthogonal Regioselective Synthesis of Folic Acid γ-Conjugates
Ciera F Connelly1, Shiao Y Chow1
1Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
Organic Letters
|November 27, 2025
Summary
Researchers developed a new method for creating targeted cancer therapies using folic acid conjugates. This strategy improves regioselectivity and simplifies purification, enabling the attachment of various functional molecules for precise drug delivery.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Cancer Biology
Background:
- Folic acid conjugates target the folate receptor, a key cancer biomarker.
- Direct folic acid conjugation faces challenges in regioselectivity and purification.
Purpose of the Study:
- To develop a regioselective method for synthesizing gamma-folic acid conjugates.
- To enable site-selective installation of functional groups for targeted cancer therapy.
Main Methods:
- An orthogonal protection strategy was employed.
- Readily available building blocks were used for synthesis.
- Functional modalities like ligands, probes, and bioorthogonal handles were installed site-selectively.
Main Results:
- Controlled regioselective access to gamma-folic acid conjugates was achieved.
- Various functional groups were successfully installed.
- Purification was simplified, avoiding reversed-phase chromatography.
Conclusions:
- The reported strategy provides efficient and regioselective synthesis of gamma-folic acid conjugates.
- This method facilitates the development of novel targeted cancer therapies.
- The approach simplifies conjugation chemistry for folate receptor-targeted agents.
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