The chemistry and structure of the P(O)NC(O) system. Part 3. Preparation of O,O‐diethyl‐N‐acylphosphoramidates and their reactions with electrophiles

CycloSal‐nucleosyl‐phosphate triesters are a known class of highly effective nucleotide prodrugs (pronucleotides) of antivirally active nucleoside analogues. Until recently, the synthesis of these compounds always gave diastereoisomeric mixtures. Then, a convergent route for the stereospecific synthesis of cycloSal‐triesters was described to give isomerically pure cycloSal‐prodrugs for the treatment of viral diseases. Here, the development of a stereoselective synthesis of these pronucleotides using various chiral auxiliaries is described. In contrast to pyrrolidine‐ or pyrrolidinone derivatives it was found that a thiazolidine derived from valinol fulfilled all three requirements to act as a suitable chiral moiety, allowing: (i) strong chirality transfer, (ii) the formation of separable diastereoisomeric intermediates, and (iii) a suitable leaving group that allows the introduction of the nucleoside analogue (e.g., d4T) in the final step under mild reaction conditions. The title compounds were obtained with very high diastereoisomeric excesses of more than 95 %.

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Influence of phase transfer catalyst structure on selectivity

Dehmlow

1995

Russ Chem Bull

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The chemistry and structure of the P(O)NC(O) system. Part 3. Preparation of O,O‐diethyl‐N‐acylphosphoramidates and their reactions with electrophiles

Cited by 10 publications

References 17 publications

ChemInform Abstract: The Chemistry and Structure of the P(O)NC(O) System. Part 3. Preparation of O,O‐Diethyl N‐Acylphosphoramidates and Their Reactions with Electrophiles.

ChemInform Abstract: The Chemistry and Structure of the P(O)NC(O) System. Part 3. Preparation of O,O‐Diethyl N‐Acylphosphoramidates and Their Reactions with Electrophiles.

Linear Synthesis of Chiral cycloSal‐Pronucleotides

Influence of phase transfer catalyst structure on selectivity

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