Question

what is the mechanism for making n-glycosidic bond into deoxy Thymadine? how does this process differ from what can or does occur in solution?

Answer 1

Biosynthesis of thymidine is done in an indirect way unlike other nucleosides. The pathway is as follows:

Uridine Monophosphate (UMP) ------> Uridine Diphosphate (UDP) ------> Deoxy Uridine Diphosphate (dUDP)

-------> Deoxy Uridine Triphosphate (dUTP) ---------->Deoxy Uridine Monophosphate (dUMP) ----------> Deoxy

Thymidine Monophosphate (dTMP).

Following enzymes are responsible for each conversion as given below:

UMP --------------> UDP            --------------- Uridine monophosphate kinase

UDP --------------> dUDP          --------------- Ribonucleotide kinase

dUDP -------------> dUTP          -------------- Deoxy uridine diphosphate kinase

dUTP --------------> dUMP        -------------- Deoxy uridine triphosphatase

dUMP -------------> dTMP         -------------    Thymidylate synthase

The resultant thymidine monophosphate is salvaged by another phosphatase to result in thymidine.

Chemical synthesis of thymidine (a.k.a. deoxy thymidine) is also done indirectly from the corresponding ribo derivative as shown in the below scheme:

As can be seen from the scheme the 3'and 5' 3' hydroxyls are protected as a first step in the ribo derivative. Then the free 2' hydroxyl group is removed chemically in the second step to obtain the deoxy ribo derivative. In the final step the 3' and 5' hydroxyl protection is removed to obtain the desired deoxy thymidine.