9] Simple methods for preparing nicotinamide mononucleotide and related analogs

Abstract

Publisher Summary This chapter describes the methods for preparing nicotinamide mononucleotide and related analogs. Nicotinamide mononucleotide (NMN) is a prerequisite in the preparation of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) analogs, of which the nonfunctional nucleotide moiety is to be modified; correspondingly, NMN analogs are necessary for preparing coenzyme models that have a modified functional moiety. There are two ways to prepare NMN: (1) cleavage of the dinucleotide NAD(P), by acid hydrolysis or by dinucleotide-nucleotidohydrolases (NAD-pyrophosphatases) and (2) total synthesis, starting with the nucleotide components nicotinamide, ribose, and phosphate. Nicotinamide nucleosides can be prepared from l-halogeno sugars and nicotinamide, or by the reaction of N1-(2,4-dinitrophenyl)-3-carba-moylpyridinium chloride with 1-amino sugars. In both cases, a mixture of anomeric nucleosides is obtained; the ratio of its constituents depends on the sugar compound. A selective phosphorylation of pyridinium nucleosides is very difficult. Either the introduction of protective groups or their removal afterward can pose problems. α-l-chloro-2,3,4-tri,-O-acetylglucopyranose has been used as the sugar compound to prepare the NMN analog nicotinamide-Nl-β- D -glucopyranosyl-6-phosphate. The free hydroxy group in the 6-position of this sugar allows the selective phosphorylation later on and the acetyl group in the cis-position to the halogen favors the formation of the β-anomer.