title: New approaches to the industrial synthesis of HIV protease inhibitors.
abstract: Efficient and industrially applicable synthetic processes for precursors of HIV protease inhibitors (Amprenavir, Fosamprenavir) are described. These involve a novel and economical method for the preparation of a key intermediate, (3S)-hydroxytetrahydrofuran, from l-malic acid. Three new approaches to the assembly of Amprenavir are also discussed. Of these, a synthetic route in which an (S)-tetrahydrofuranyloxy carbonyl is attached to l-phenylalanine appears to be the most promising manufacturing process, in that it offers satisfactory stereoselectivity in fewer steps.
authors.affiliation: AminoScience Laboratories, Ajinomoto Co., Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi 210-8681, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Honda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Katayama
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Kojima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Naomi
authors.initials: N
authors.lastname: Kishibata
authors.forename: Kunisuke
authors.initials: K
authors.lastname: Izawa
mesh_terms: D002219:Carbamates; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis*; D008968:Molecular Conformation; D015394:Molecular Structure; D010755:Organophosphates / Q000138:chemical synthesis*; D013449:Sulfonamides / Q000138:chemical synthesis*
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D013449:Sulfonamides; C095108:amprenavir; C426859:fosamprenavir