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Study On The Chemical Synthesis Of Coenzyme Ⅰ And Its Intermediate

Posted on:2014-11-25Degree:MasterType:Thesis
Country:ChinaCandidate:Q H PanFull Text:PDF
GTID:2251330425984112Subject:Pharmaceutical Engineering
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Coenzyme I (Nicotinamide Adenine Dinucleotide, NAD+), as dehydrogenase, plays an important role of transmitting hydride ions and electrons to the substrate, which makes coenzyme I irreplaceable during various cellular processes.In its chemical structure, NAD+maintains a phosphoric anhydride bond, which connects two5’-nucleotides, i.e. Adenosine monophosphate (AMP) and β-Nicotinamide Mononucleotide (β-NMN). Recent reports showed that the synthesis of NAD+nowadays still mainly depends on biocatalysis method. It is an accurate analog of in vivo biological metabolism to make the use of specific enzymes to achieve the expectant biosynthesis. Harsh conditions during the biocatalesis method normally results in an expensive cost, which makes searching for a feasible, convenient and economic chemical synthesis method imperative.Our study summarized recent synthesis of NAD+and its intermediates. Depended on summary, we selected synthetic routes, and divided NAD+synthesis into two main parts:1. synthesis of its intermediates (AMP and β-NMN);2. AMP and β-NMN form NAD+by coupling reaction. After the study on chemical synthesis processes and reaction conditions, we screened an optimal synthetic condition.Intermediates p-NMN and AMP synthesis were based on the Vorbruggen nucleoside reaction. Theβ-NMN’s synthesis contained ribose acetylation, silylation protected organic base catalyzed by SnCl4to stereoselectively generate β-nucleoside, then deprotection and phosphorylation to form nucleotide. The β-NMN, afterwards, coupled with AMP to generate final NAD+molecule. The AMP was activated by phosphate to increase its affinity. Our study reached a feasible and economic chemical synthetic method to synthesize NAD+with short reaction time and considerable yield.
Keywords/Search Tags:Coenzyme, NAD~+, nucleotides, Vorbruggen nucleoside reaction
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