Stec reaction

What is Stec reaction?

The Stec reaction was initially documented by Stec et al. in 1976, and it is a stereospecific approach for creating P-chiral biophosphates using carbonyl electrophiles and dialkyl (or aryl) phosphoramidate anions, which is then accompanied by the exchange of an amidate function with oxygen. Consequently, this reaction is commonly referred to as the Stec reaction, and it can also replace the amidate function with sulfur and selenium, which is labeled as the Stec reaction PN → PX (X = S, Se).

Stec reaction - general reaction scheme
Stec reaction

The Stec reaction has been used to develop enantiomerically pure anticancer drugs, such as cyclophosphamide and isophosphamide, by segregating cyclic phosphoramidate diastereomers, in which a chiral auxiliary from α-phenylethylamine was subsequently eliminated by hydrogenolysis.

Furthermore, this method enables the production of diverse diastereomerically pure P-chiral biophosphates and their analogues, such as phosphorothioates, phosphoroselenoates, phosphoroselenothioates, isotopomeric 18O-phosphates, P-chiral nucleoside monophosphate analogues, and dinucleoside phosphate analogues (phosphorothioates, methanephosphonates), while retaining their configuration at the phosphorus atom. Many of these phosphate derivatives are difficult to prepare by other techniques.

The Stec reaction is particularly useful in the stereoconvergent synthesis of stereodefined methanephosphonate analogues of nucleic acid, with a predetermined chirality at the internucleotide phosphorus atoms.

References

  • Stec,W. J.; Okruszek, A. and Michalski, J., J. Org. Chem., 1976, 41, 233
  • Zielinski,W. S.; Lesnikowski, Z. J. and Stec, W. J., J. Chem. Soc., Chem. Commun., 1976, 772
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