Synthesis of methylene-bridged analogues of nicotinamide riboside, nicotinamide mononucleotide and nicotinamide adenine dinucleotide

Article abstract of DOI:10.1080/07328319608002377

5-O-tert-Butyldimethylsilyl-1,2-O-isopropylidene-3(R)-(nicotinamid-2-y lmethyl)-D-ribofuranose (11a) and -3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose (11b) were prepared by condensation of 5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-α-D-erythro-3-pentul ofuranose (10) with lithiated (LDA) 2-methylnicotinamide and 6-methylnicotinamide, respectively, and then deprotected to give 1,2-O-isopropylidene-3-(R)-(nicotinamid-2-ylmethyl)-α-D-ribofuranose (12a) and 1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose (12b). Benzoylation as well as phosphorylation of compounds 12 afforded the corresponding 5-O-benzoate (13b) and 5-O-monophosphates (14a and 14b). Treatment of 13b with CF₃COOH/H₂O caused 1,2-de-O-isopropylidenation with simultaneous cyclization to the corresponding methylene-bridged cyclic nucleoside - 3',6-methylene-1-(5-O-benzoyl-β-D-ribofuranose)-3-carboxamidopyridini um trifluoro-acetate (8b) - restricted to the 'anti' conformation. In a similar manner compounds 14a and 14b were converted into conformationally restricted 2,3'-methylene-1-(β-D-ribofuranose)-3-carboxamidopyridinium-5'-monoph osphate (9a-'syn') and 3',6-methylene-1-(β-D-ribofuranose)-3-carboxamidopyridinium-5'-monoph osphate (9b-'anti') respectively. Coupling of derivatives 12a and 12b with the adenosine 5'-methylenediphosphonate (16) afforded the corresponding dinucleotides 17. Upon acidic 1,2-de-O-isopropylidenation of 17b, the conformationally restricted P¹-[6,3'-methylene-1-(β-D-ribofuranos-5-yl)-3-carboxamidopyridinium] -P²-(adenosin-5'-yl)methylenediphosphonate 18b-'anti' was formed. Compound 18b was found to be unstable. Upon addition of water 18b was converted into the anomeric mixture of acyclic dinucleotides, i.e. P¹-[3(R)-nicotinamid-6-ylmethyl-D-ribofuranos-5-yl]-P²-(adenosin-5'- yl)methylenediphosphonate (19b). In a similar manner, treatment of 17a with CF₃COOH/H₂O and HPLC purification afforded the corresponding dinucleotide 19a.

Full text of DOI:10.1080/07328319608002377

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Synthesis of Methylene-Bridged
Analogues of Nicotinamide Riboside,
Nicotinamide Mononucleotide and
Nicotinamide Adenine Dinucleotide
Pawel Lipka a , Andrzej Zatorski a , Kyoichi A. Watanabe a &
Krzysztof W. Pankeiwicz a
a Laboratory of Organic Chemistry , Sloan-Kettering Institute
for Cancer Research , Memorial Sloan-Kettering Cancer Center;
Sloan-Kettering Division, Graduate School of Medical Sciences,
Cornell University, New York, NY, 10021
Published online: 21 Aug 2006.
To cite this article: Pawel Lipka , Andrzej Zatorski , Kyoichi A. Watanabe & Krzysztof W.
Pankeiwicz (1996) Synthesis of Methylene-Bridged Analogues of Nicotinamide Riboside,
Nicotinamide Mononucleotide and Nicotinamide Adenine Dinucleotide , Nucleosides and
Nucleotides, 15:1-3, 149-167
To link to this article: http://dx.doi.org/10.1080/07328319608002377
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