Novel Baeyer–Villiger Oxidation of Nucleosides Applied to the Large-Scale Synthesis of MeMOP: A Key Amidite in the GalXC Platform

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-03-27 DOI:10.1021/acs.oprd.5c00021

John R. Rizzo, Prem Kumar Begari, Deepak Kalita, Jiancai Gu, Scott A. Frank, Nour Eddine Fahmi, Hem Raj Khatri

引用次数: 0

Abstract

The Baeyer–Villiger reaction is an established oxidative process that is applied for structural and functional group modification. We have applied the Baeyer–Villiger process to prepare 4′-oxo nucleosides. The application of Baeyer–Villiger oxidation to prepare MeMOP, a complex amidite used in the reported GalXC platform, will be discussed. A large-scale process to prepare MeMOP with an improved economic and operational safety risk profile will be highlighted. This novel application of the Baeyer–Villiger reaction to nucleoside platforms was used to scale up the MeMOP phosphoramidite process, which supported multiple clinical trials enabling siRNA campaigns.

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新型Baeyer-Villiger氧化核苷在大规模合成MeMOP中的应用：GalXC平台上的关键中间体

Baeyer-Villiger反应是一种已建立的用于结构和官能团修饰的氧化过程。我们已经应用Baeyer-Villiger工艺制备了4′-氧基核苷。本文将讨论Baeyer-Villiger氧化法制备MeMOP（一种用于GalXC平台的复合中间体）的应用。将重点介绍一个大规模的过程，以制备具有改进的经济和操作安全风险的MeMOP。这种Baeyer-Villiger反应在核苷平台上的新应用被用于扩大MeMOP磷酰胺工艺，该工艺支持多个临床试验，使siRNA运动成为可能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.