Nucleoside 5 -phosphoromorpholidates

When AMP is heated under reflux in DMF, the 2, 3 -cyclic phosphate is formed, and cyclic phosphates can also be obtained from nucleosides and ortho-, pyro-, or poly-phosphoric acids under the same conditions. Promotion of phosphorylation by DMF is well known and the reaction with AMP is probably intermolecular as no 3, 5 -cyclic AMP can be detected. Minor products in the latter reaction are the 2, 3 -cyclic 5 -diphosphate and the 2 (30,5 -diphosphate. The synthesis of adenosine 2 (3 )-phosphate 5 -pyrophosphate has been achieved by the phosphoromorpholidate method used in a synthesis of Co A. ... 

Phosphoromorpholidate intermediates, initially developed by Khorana and Moffatt,19 have been widely used for the construction of nucleoside diphosphates. The construction of the diphosphate linkage typically involves exposure of a carbohydrate-derived phosphate nucleophile to phosphoromorpholidate electrophile in pyridine solvent. This protocol was attractive from the point of view that it can be executed on completely deprotected precursors. This method suffers, however, from the lengthy reaction times required for reasonable conversion, although a tetrazole modification, introduced by Wong, had been shown to shorten reaction times considerably. The major drawback of this method, for our own purposes, is that it would require construction of either a carbohydrate-derived phosphoromorpholidate or the preparation of a phosphoromorpholidate intermediate deriving from our rather expensive undecaprenyl monophosphate precursor. 

Diphosphoric acid esters from phosphoromorpholidates Nucleoside diphosphates... 

---