立体选择性合成p -立体核苷酸前药和寡核苷酸

IF 39 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jia-Bao Wang, Ji Yuan Lv, Siddheshwar Kisan Bankar, Shuai-Shuai Fang, Ming Shang
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引用次数: 0

摘要

磷(V)立体中心在严重疾病的治疗策略中起着至关重要的作用,包括病毒感染、慢性疾病和罕见的遗传疾病。这些疾病通常涉及基因相关病理或由影响细胞内代谢过程的基因突变引起。脯氨酸和反义寡核苷酸疗法是治疗此类疾病最有效的策略之一,其中磷中心的绝对构型与治疗效果直接相关。然而,由于缺乏有效和可扩展的合成方法,立体定义的ProTides和ps寡核苷酸的开发仍然是一个重大的挑战。本文综述了实现立体控制合成磷基脯氨酸和ps寡核苷酸的各种方法,包括使用立体纯前体、手性助剂、不对称催化和酶的方法。通过推进这些策略,研究人员可以提高基于核苷酸的治疗方法的立体化学精度,最终提高其临床潜力。此外,本文综述了目前用于工业规模生产p -立体原性蛋白酶和寡核苷酸的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Stereoselective synthesis of P-stereogenic nucleotide prodrugs and oligonucleotides

Stereoselective synthesis of P-stereogenic nucleotide prodrugs and oligonucleotides
Phosphorus(V) stereocenters play a crucial role in the therapeutic strategies for severe diseases, including viral infections, chronic conditions, and rare genetic disorders. These diseases often involve gene-related pathologies or arise from genetic mutations that affect intracellular metabolic processes. ProTide and antisense oligonucleotide therapies are among the most effective strategies for treating such conditions, where the absolute configuration of the phosphorus center is directly linked to therapeutic efficacy. However, the development of stereodefined ProTides and PS-oligonucleotides remains a significant challenge due to the lack of efficient and scalable synthetic methodologies. This review highlights various approaches for achieving stereocontrolled synthesis of phosphorus-based ProTides and PS-oligonucleotides, including the use of stereopure precursors, chiral auxiliaries, asymmetric catalysis and enzymatic approaches. By advancing these strategies, researchers can improve the stereochemical precision of nucleotide-based therapeutics, ultimately enhancing their clinical potential. Moreover, this review examines the current methodologies utilized for the industrial-scale production of P-stereogenic ProTides and oligonucleotides.
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来源期刊
Chemical Society Reviews
Chemical Society Reviews 化学-化学综合
CiteScore
80.80
自引率
1.10%
发文量
345
审稿时长
6.0 months
期刊介绍: Chemical Society Reviews is published by: Royal Society of Chemistry. Focus: Review articles on topics of current interest in chemistry; Predecessors: Quarterly Reviews, Chemical Society (1947–1971); Current title: Since 1971; Impact factor: 60.615 (2021); Themed issues: Occasional themed issues on new and emerging areas of research in the chemical sciences
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