Oxygen → D-o-Tyrosine

Commercially available DL-o-tyrosine 1 (Fluka) is treated with L-aminoacid oxidase and oxygen according to the procedure of Sun et al. (J. Med. Chem. 1998, 41, 1034-1041) to afford the D-o-tyrosine 2. Reaction with di-t-butyl-dicarbonate in the presence of base affords the boc protected amino acid 3 (J. Med. Chem. 1998, 41, 1034-1041). The boc protected acid 3 is then treated with benzyl bromide in the presence of potassium carbonate to afford the benzyl ether 4 (J. Med. Chem. 1998, 41, 1034-1041). The four step sequence reported for the preparation of the corresponding epoxide of phenylalanine (see J. Med. Chem. 1994, 37, 1758-1768) is used to prepare the desired epoxides. Thus, the acid 4 is treated with isobutylchloroformate in the presence of N-methylmorpholine to afford the mixed anhydride which is then treated with diazomethane to afford the α-diazoketone 5 (see scheme 1). The ketone 5 is treated with HCl to form the α-chloroketone 6 which is then reduced with sodium borohydride to form the chloro alcohol 7. The 2S, 3R diastereoisomer is separated by chromatography and treated with base (e.g. potassium hydroxide) to afford the epoxide 8.

ORD record

ord-0c659f4f63154da6a2571687dcb3b5a2

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07649015B2