Uridine ring synthesis

The major intermediates in the biosynthesis of nucleic acid components are the mononucleotides uridine monophosphate (UMP) in the pyrimidine series and inosine monophosphate (IMP, base hypoxanthine) in the purines. The synthetic pathways for pyrimidines and purines are fundamentally different. For the pyrimidines, the pyrimidine ring is first constructed and then linked to ribose 5 -phosphate to form a nucleotide. By contrast, synthesis of the purines starts directly from ribose 5 -phosphate. The ring is then built up step by step on this carrier molecule. 

The common pyrimidine ribonucleotides are cytidine 5 -monophosphate (CMP cytidylate) and uridine 5 -monophosphate (UMP uridylate), which contain the pyrimidines cytosine and uracil. De novo pyrimidine nucleotide biosynthesis (Fig. 22-36) proceeds in a somewhat different manner from purine nucleotide synthesis the six-membered pyrimidine ring is made first and then attached to ribose 5-phosphate. Required in this process is carbamoyl phosphate, also an intermediate in the urea cycle (see Fig. 18-10). However, as we noted... 

The reaction has been applied to the synthesis of C-2, C-3 branched-chain uridine derivatives of either lyxo 67a or ribo configuration 67b. Interestingly, only one diastereo-isomer 68a is formed when the olefin chain is located on the (3-face of the furanose ring lyxo configuration), whereas a mixture of the two possible diastereoisomers 68b is obtained when the olefin is located on the a-face ribo configuration) [91] (see Scheme 26). 

The enzyme DNA polymerase, which uses deoxynucleoside triphosphates as substrates, makes DNA. To ensure enough precursors for DNA synthesis, two reactions must occur. First, the 2 position of the ribose ring of ribonucleotides must be reduced from a C-OH to a C-H before the nucleotides can be used for DNA synthesis. Secondly, the thymine ring must be made by addition of a methyl group to uridine. 

Uridine and A -benzyluridine have been reported to show sleep-promoting activity [37] and hypnotic activity [38], respectively. We have been very interested in this topic and have studied the hypnotic activity of A3-substituted 2 -deoxy-2 -a-fluorouridines to determine their SAR trends. For the synthesis of the key compound 4 (2 -deoxy-2 -a-fluorou-ridine), an alternative synthetic route via arabinoside was developed since a previously reported method [39] involving a ring-cleavage reaction of 2,2 -O-cyclouridine (3, X = H) required severe reaction conditions, such as exposure to HF (see Scheme 7.1). The new route is illustrated in Scheme 7.7. The hydroxyl groups of 2,2 -O-cyclouridine (3) were... 

C-labelled glycines have been prepared " from the corresponding bromoacetic acids , used in the synthesis of the 2, 3, 5 -tri-C)-benzoyl[4- C]uridine and regiospecific introduction of isotopic carbon or nitrogen into one or more positions of the pyrimidine ring . [ N]glydne has been prepared from potassium [ N]phthalimide . 

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