Chiral Analysis of the Key Intermediates of Tenofovir Alafenamide Fumarate

Abstract (R)-Tenofovir phenyl ester ((R)-1) and (R)-tenofovir diphenyl ((R)-2) are key intermediates for the practical synthesis of tenofovir alafenamide fumarate, which is a mainstay antiretroviral treatment chronic hepatitis B HIV-1 infections. This article deals with chiral analysis (R)-1 (R)-2 against their respective optical impurity (S)-tenofovir ((S)-1) ((S)-2) using polysaccharide-coated stationary phase (CSP) by normal-phase high-performance liquid chromatography (HPLC). To this end, synthetic strategy (S)-2 was efficiently executed capitalizing on classical Mitsunobu reaction to stereospecifically invert configuration carbon in readily accessible (R)-HPA ((R)-4) deliver (S)-HPA ((S)-4), from (S)--tenofovir ((S)-3) turn prepared further transformed into (S)-2. With reference substance hand, analytical method Chiralpak AD-H as CSP HPLC has been developed validated. The validation results indicated that achieved satisfactory separation effect, high sensitivity, good precision accuracy, thus can be deployed determination impurities samples (via derivation (R)-2) (R)-2.