Kinetic Studies to Enable a Scalable Direct Glycosylation of a GalNAc Donor

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-02-27 DOI:10.1021/acs.oprd.4c00487

Shea J. O’Sullivan, James I. Murray, Eric Kircher, Zhou Li, Tsang-Lin Hwang, Seb Caille, Janine K. Tom

引用次数: 0

Abstract

A direct glycosylation was developed to enable the supply of a key intermediate in the synthesis of a targeting N-acetylgalactosamine (GalNAc) ligand. Kinetic experiments were performed to elucidate possible mechanistic differences between transformations catalyzed by two potential metal triflate catalysts, revealing a change in the rate-limiting step upon alteration of the metal center. Selection of a bismuth triflate catalyst led to a more efficient and robust process, which halved the number of unit operations, reduced solvent waste by 70%, and increased the isolated yield by 60% compared to traditional indirect glycosylation conditions.

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GalNAc供体可扩展直接糖基化的动力学研究

通过直接糖基化，为n -乙酰半乳糖胺（GalNAc）配体的合成提供了关键中间体。通过动力学实验，阐明了两种潜在的三氟化金属催化剂催化转化的机理差异，揭示了金属中心改变时限速步的变化。与传统的间接糖基化条件相比，三酸铋催化剂的选择使工艺更高效、更稳健，使单元操作次数减少了一半，溶剂浪费减少了70%，分离收率提高了60%。

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.