Facile Synthetic Route to (2S,3S)‐3‐Amino‐2‐hydroxy‐4‐phenylbutyric Acid and Its Derivatives, the Key Intermediates for HIV Protease Inhibitors

Abstract

A facile and efficient route to (2S,3S)‐3‐amino‐2‐hydroxy‐4‐phenylbutyric acid and its derivative (4S,5S)‐4‐benzyl‐5‐hydroxymethyl oxazolidin‐2‐one is presented. N‐phthaloyl protected L‐phenylalanine 1 was treated with thionyl chloride followed by hydrogenation of the acyl chloride 2 on Pd/C, giving (S)‐2‐phthalimido‐3‐phenylpropionaldehyde 3. Aldehyde 3 reacted with Nagata's reagent to afford 3‐phthalimido‐2‐hydroxy‐4‐phenylbutyronitrile 4 as a diastereomeric mixture. After hydrolysis, protection, esterification, and reduction, 4 was transformed into the optically pure compound 7 in good yield.

Keywords:

• AHPBA
• HIV protease inhibitors
• Nagata's reagent
• N‐phthaloyl protecting group