Phosphates Cleaved by Cyclodeesterification

4-Methylthio-l-butyl group is prepared by the standard phosphoramidite method. Oxidation must be done using I2 in pyridine rather than hydroperoxides because these will also oxidize the sulfide to the sulfoxide. Cleavage is accomplished by heating the phosphate ester to 55°C for 30 min.  

Ammonia treatment removes the TFA group, which then through intramolecular cyclization releases the phosphate and pyrrolidine. The analogous pentyl derivative was also prepared but the cleavage rate was slower.  

The SATE group is compatible with the fluoride labile trimethylsilylethyl and the [r-butyldiphenylsiloxymethyl]benzoyl groups during oligonucleotide synthesis.  

The SATE ester is formed from a phosphite using PvCl activation followed by oxidation to the phosphate with I2/H20.  

Enzymatic hydrolysis exposes the sulfide that undergoes episulflde formation by cyclodeesteriflcation releasing the phosphate. This method was developed for intracellular delivery of a monophosphate. This concept was also extended to the use of an 5-glucoside (GTE group) that could be activated by a glucosi-dase to release the thiol.  

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