New approaches to the industrial synthesis of HIV protease inhibitors.
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.
Honda
Yutaka
Y
AminoScience Laboratories, Ajinomoto Co., Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi 210-8681, Japan.
Katayama
Satoshi
S
Kojima
Mitsuhiko
M
Suzuki
Takayuki
T
Kishibata
Naomi
N
Izawa
Kunisuke
K
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*
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D013449:Sulfonamides; C095108:amprenavir; C426859:fosamprenavir