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Scale-Up of a Heck Alkenylation Reaction: Application to the Synthesis of an Amino-Modifier Nucleoside ‘Ruth Linker’
Synthesis ( IF 2.6 ) Pub Date : 2020-09-08 , DOI: 10.1055/s-0040-1707260
Anant R. Kapdi 1 , Shatrughn Bhilare 1 , Santosh Kori 1, 2 , Harshita Shet 1, 2 , Gundapally Balaram 3 , Koosam Mahendar 3 , Yogesh S. Sanghvi 4
Affiliation  


Dedicated to the memory of Jerry Lynn Ruth who first demonstrated the utility of this molecule for DNA labeling

Abstract

Ruth linker is a C5 pyrimidine modified nucleoside analogue widely utilized for the incorporation of a primary amine in a synthetic oligonucleotide. The increasing demand for non-radioactive labeling, detection of biomolecules, and assembly of COVID-19 test kits has triggered a need for scale-up of Ruth linker. Herein, an efficient protocol involving a palladium-catalyzed Heck alkenylation is described. The synthesis has been optimized with a goal of low catalyst concentration, column-free isolation, high product purity, reproducibility, and shorter reaction time. The scalability and utility of the process have been demonstrated successfully on a 100 g scale (starting material). Additionally, for scale-up of the Heck alkenylation protocol, 7-phospha-1,3,5-triaza-adamantanebutane sulfonate (PTABS) as the coordinating caged phosphine ligand was also synthesized on a multigram scale after careful optimization of the conditions.



Publication History

Received: 06 June 2020

Accepted after revision: 01 August 2020

Publication Date:
08 September 2020 (online)

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany



中文翻译:

Heck烯基化反应的规模放大:在氨基修饰剂核苷“ Ruth接头”的合成中的应用


致力于纪念杰里·林恩·露丝(Jerry Lynn Ruth),他首先展示了该分子在DNA标记中的用途

抽象

露丝接头是C5嘧啶修饰的核苷类似物,广泛用于在合成寡核苷酸中掺入伯胺。对非放射性标记,生物分子检测以及COVID-19测试试剂盒的组装的需求不断增长,引发了对Ruth接头规模扩大的需求。在本文中,描述了涉及钯催化的Heck烯基化的有效方案。为了达到低催化剂浓度,无柱分离,高产物纯度,可重复性和缩短反应时间的目标,对合成进行了优化。该方法的可扩展性和实用性已在100 g规模(原材料)上得到了成功证明。此外,为了扩大Heck烯基化协议,7-phospha-1,3,



出版历史

收到:2020年6月6日

修订后接受:2020年8月1日

发布日期:
2020年9月8日(在线)

©2020年。Thieme。版权所有

Georg Thieme Verlag
KGRüdigerstraße14,70469斯图加特,德国

更新日期:2020-09-10
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