| Abstract
| - Both the (R)- and (S)-5‘-hydroxy 5‘-phosphonate derivatives of cytidine and cytosine arabinoside(ara-C) have been prepared via phosphite addition or a Lewis acid mediated hydrophosphonylationof appropriately protected 5‘-nucleoside aldehydes. Phosphite addition to a cytosine aldehydeprotected as the 2‘,3‘-acetonide gave predominately the 5‘R isomer, while phosphite addition tothe corresponding 2‘,3‘-bis TBS derivative favored the 5‘S stereochemistry. In contrast, phosphiteaddition to the 2‘,3‘-bis TBS protected aldehyde derived from ara-C gave only the 5‘R adduct.However, TiCl4-mediated hydrophosphonylation of the same ara-C aldehyde favored the 5‘Sstereoisomer by a 2:1 ratio. Once all four of the diastereomers were in hand, the stereochemistryof these compounds could be assigned based on their spectral data or that obtained from theirO-methyl mandelate derivatives. After hydrolysis of the phosphonate esters and various protectinggroups, the four α-hydroxy phosphonic acids were tested for their ability to serve as substrates forthe enzyme nucleoside monophosphate kinase and for their toxicity to K562 cells.
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