Synlett 2014; 25(16): 2331-2336
DOI: 10.1055/s-0034-1379000
letter
© Georg Thieme Verlag Stuttgart · New York

Nicotinamide Benzimidazolide Dinucleotides, Non-Cyclisable Analogues of NAD+

Philip Redpath
a  Queen’s University Belfast, John King Laboratory, School of Pharmacy, Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK   Fax: +44(28)90247794   Email: m.migaud@qub.ac.uk
,
Jolanta Haluszczak
a  Queen’s University Belfast, John King Laboratory, School of Pharmacy, Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK   Fax: +44(28)90247794   Email: m.migaud@qub.ac.uk
,
Simon J. Macdonald
b  GlaxoSmithKline, Stevenage, SG1 2NY, UK
,
Marie E. Migaud*
a  Queen’s University Belfast, John King Laboratory, School of Pharmacy, Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK   Fax: +44(28)90247794   Email: m.migaud@qub.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 04 June 2014

Accepted after revision: 24 July 2014

Publication Date:
26 August 2014 (online)


Abstract

Benzimidazole-based nucleotides and dinucleotides have been synthesised to increase the range of chemical tools available to probe the NAD+ biology space. They were examined for their reactivity in alkylation-type reactions, where they yielded unstable alkylated heteoaromatic adducts, both chemically and enzymatically. While unsuited for NAD+ cyclases, these NAD+ analogues could be viable substrates for non-adenine modifying NAD+-dependent enzyme classes.

 
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  • 43 Nicotinamide 5-Phenylbenzimidazole Dinucleotide (26): The product was isolated after 48 h in 43% of yield. 1H NMR (400 MHz, D2O): δ = 8.86 (s, 1 H), 8.67 (s, 1 H), 8.58 (s, 2 H), 8.09 (s, 1 H), 7.85 (s, 1 H), 7.29–7.68 (m, 9 H), 5.91 (s, 1 H), 5.52 (s, 1 H), 3.94–4.42 (m, 10 H). 31P NMR (162 MHz, D2O): δ = –11.09 to –11.60 (m, P–O–P). HPLC: t R = 8.87 min. MS (ES): m/z [M]+ calcd for C29H33N4O14P2 +: 723.1469; found: 723.1436.
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