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Total Synthesis of Flavin-adenine-dinucleotide

Abstract

FLAVIN-ADENINE-DINUCLEOTIDE (FAD) is the coenzyme of a number of flavoprotein enzymes functioning as oxidation-reduction catalysts in biological systems. Isolated in 1938 by Warburg and Christian1, it was assigned a probable structure (I) on the basis of available degradative evidence, although its preparation in a pure state has probably been rarely accomplished since its original isolation. Flavin-adenine-dinucleotide is structurally related to several other equally complex coenzymes (for example, coenzymes I and II, uridine-diphosphate-glucose and coenzyme A) in that all of them appear to be diesters of pyrophosphoric acid, in which one ester group embraces a pyrimidine or purine nucleoside residue, and indeed the members of the group are usually described loosely as nucleotide coenzymes. No chemical synthesis of any of these coenzymes has hitherto been achieved, although both flavin-adenine-dinucleotide and coenzyme-I have been prepared by enzymic reactions2.

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CHRISTIE, S., KENNER, G. & TODD, A. Total Synthesis of Flavin-adenine-dinucleotide. Nature 170, 924 (1952). https://doi.org/10.1038/170924a0

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