Biomimetic Base-Exchange Reaction for Late-Stage Synthesis of Stereodivergent NAADP+ and NAD(P)+ Derivatives.

Nicotinic acid adenine dinucleotide phosphate (NAADP+) and related NAD(P)+ analogues are important tools for calcium signaling, redox biology, and chemical biology. Their preparation, however, remains constrained by lengthy dinucleotide synthesis and enzyme-dependent base exchange. Here we describe a biomimetic chemical base-exchange reaction that converts native NAD+ or NADP+ directly into NAAD+, NAADP+, and modified pyridine nucleotide analogues. Fe(III) promotes substitution of the nicotinamide unit through synergistic activation of the cationic C-N glycosidic bond.