Thymidine selective acetylation

Protection of a hydroxyl group at C-5 in a nucleoside has been performed161 by using crotonic (2-butenoic) and related esters. A remarkably selective removal of the 5 -0-acyl group was observed on treatment of 3 -0-acetyl-5 -0-(4-methoxycrotonoyl)thymidine with 0.05 M hydrazine hydrate in methanol-pyridine for 2 hours at 20°. 

The conformationally-locked 3 -amino thymidine derivative (47) was prepared and incorporated into DNA as a dimer unit, attaching the amino group via a carbamate or phosphoramidate linkage.Both modifications were found to be destabilising towards both RNA and DNA targets. The hybridisation properties of an amino-modified bicyclic thymine nucleotide (48) have been exam-ined. Using alternate T and (48) residues there is an increase in duplex stability with d(A)io, with no pH dependence. When the amino group is acetylated, the duplex stability is decreased. The locked C-nucleoside oxazole derivative (49) has been incorporated into TFOs where it was found to selectively enhance the stability with a C.G base pair. ... 

Enzymic acetylation of thymidine and deoxyuridine using vinyl acetate and an engineered mutant of subtilisin gives the S -(9-acetyl derivatives specifically,247 whilst the lipase from Candida cylindraceae catalyses the selective hydrolysis of the 3 -0-acetyl group of 3, 5 -di-0-acetylthymidine. Use of porcine pancreatic lipase, on the other hand, selectively hydrolyses the 5 -0-acetyl group.248 Selective enzymic acetylation at 0-5 has also been reported for zeatin 2 -deoxyriboside.249... 

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