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Synlett 2014; 25(16): 2331-2336
DOI: 10.1055/s-0034-1379000
DOI: 10.1055/s-0034-1379000
letter
Nicotinamide Benzimidazolide Dinucleotides, Non-Cyclisable Analogues of NAD+
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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References and Notes
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- 41 Nicotinamide Benzimidazole Dinucleotide (25): The product was isolated after 48 h in 32% of yield. 1H NMR (400 MHz, D2O): δ = 9.12 (s, 1 H), 8.98 (d, J = 6.2 Hz, 1 H), 8.61 (d, J = 8.1 Hz, 1 H), 8.38 (s, 1 H), 7.94–8.07 (m, 1 H), 7.58 (d, J = 7.58, 15.6 Hz, 2 H), 7.25–7.34 (m, 3 H), 6.98 (d, J = 7.8 Hz, 1 H), 5.91 (dd, J = 5.9, 9.3 Hz, 2 H), 3.98–4.51 (m, 10 H). 13C NMR (100 MHz, D2O): δ = 180.0, 171.0, 145.4, 142.1, 142.1, 139.7, 133.4, 129.9, 128.5, 124.2, 123.5, 121.6, 119.1, 114.9, 111.5, 99.9, 88.2 (d), 83.7 (d), 77.5, 72.9, 70.4, 70.10, 65.59 (d), 64.81 (d). 31P NMR (162 MHz, D2O): δ = –10.95 to –12.08 (m, P–O–P). MS (ES): m/z [M – H]– calcd for C23H28N4O14P2: 646.1077; found: 646.1078. HPLC: t R = 7.17 min.
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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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