Work

Controlling para -Quinone Methide Alkylation Impurities with Thiols during Phosphorodiamidate Morpholino Oligomer Synthesis

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide The use of doubly protected morpholino guanosine in the synthesis of PMO sequences generates a reactive para -quinone methide byproduct upon deprotection with concentrated ammonium hydroxide. Thiols are explored as potential scavengers to control the formation of PMO-alkylation impurities caused by para -quinone methide. The optimal concentration of thiol for effective control is determined.

Source: Organic Process Research & Development

DOI: 10.1021/acs.oprd.5c00176

Authors: Grace Cormier, Gopal R. Bommineni, Jurjus Jurayj, Bao Zhong Cai

Institution: Sarepta Therapeutics (United States)

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funder: Sarepta Therapeutics