Synthesis 2020; 52(23): 3595-3603
DOI: 10.1055/s-0040-1707260
psp

Scale-Up of a Heck Alkenylation Reaction: Application to the Synthesis of an Amino-Modifier Nucleoside ‘Ruth Linker’

Shatrughn Bhilare
a  Department of Chemistry, Institute of Chemical Technology, Nathalal Parekh Road, Matunga, Mumbai 400019, India   Email: ar.kapdi@ictmumbai.edu.in
,
Santosh Kori
a  Department of Chemistry, Institute of Chemical Technology, Nathalal Parekh Road, Matunga, Mumbai 400019, India   Email: ar.kapdi@ictmumbai.edu.in
b  Institute of Chemical Technology-Indian Oil Odisha Campus, IIT Kharagpur Extension Centre, MouzaSamantpuri, Bhubaneswar 751013, Odisha, India
,
Harshita Shet
a  Department of Chemistry, Institute of Chemical Technology, Nathalal Parekh Road, Matunga, Mumbai 400019, India   Email: ar.kapdi@ictmumbai.edu.in
b  Institute of Chemical Technology-Indian Oil Odisha Campus, IIT Kharagpur Extension Centre, MouzaSamantpuri, Bhubaneswar 751013, Odisha, India
,
Gundapally Balaram
c  Sapala Organics Pvt. Ltd., Plots Nos. 1468 & 147, IDA Mallapur, Phase-II, Hyderabad 500076, Telangana, India
,
Koosam Mahendar
c  Sapala Organics Pvt. Ltd., Plots Nos. 1468 & 147, IDA Mallapur, Phase-II, Hyderabad 500076, Telangana, India
,
Yogesh S. Sanghvi
d  Rasayan Inc., 2802, Crystal Ridge Road, Encinitas, CA 92024-6615, USA
,
a  Department of Chemistry, Institute of Chemical Technology, Nathalal Parekh Road, Matunga, Mumbai 400019, India   Email: ar.kapdi@ictmumbai.edu.in
› Author Affiliations


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.

Supporting Information



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

 
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