A concise synthesis of isoguanine 2’-deoxyriboside and its adenine-like triplex formation when incorporated into DNA

Abstract

A concise synthesis of 2’-deoxyisoguanosine is achieved whereby 2,6-dichloropurine is glycosylated using the Hoffer sugar to give a pair of beta-configured nucleoside N9/N7 regioisomers that are aminated using methanolic ammonia with concomitant deprotection of the sugar. Following chromatographic separation, pure 2-chloro-2’-deoxyadenosine was isolated as a single isomer. Displacement of the C2 chlorine atom using sodium benzyloxide, followed by hydrogenolysis of the benzyl group, gives 2’-deoxyisoguanosine. Isoguanine was incorporated into DNA by solid supported synthesis using the suitably protected 2-allyloxy-2’-deoxyadenosine phosphoramidite with the allyl group being removed post-oligomerisation under Noyori conditions. DNA melting studies showed isoguanine to exhibit adenine-like triplex formation.

Publication DOI: https://doi.org/10.24820/ark.5550190.p011.460
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Additional Information: Published work is permanently available free to readers under a CC-BY license
Uncontrolled Keywords: 2'-deoxyisoguanosine,Adenine,Glycosylation,Hoffer sugar,Isoguanine,Phosphoramidite,Triplex,Organic Chemistry
Full Text Link:
Related URLs: https://www.ark ... 550190.p011.460 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2021-02-14
Published Online Date: 2021-01-18
Accepted Date: 2021-01-18
Authors: Walsh, Andrew J.
Schwalbe, Carl H.
Fraser, William (ORCID Profile 0000-0001-6588-0166)

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License: Creative Commons Attribution

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