Stereoselective synthesis of unnatural spiroisoxazolinoproline-based amino acids and derivatives.
A route to spiroisoxazolinoproline-based amino acid derivatives is reported in which exo-methyleneprolinate 4 (tert-butyl ester) reacts as a dipolarophile with nitrile oxides to generate spiroisoxazolinoprolinates 7/10/11 in good yields (70-75%) and with ca. 1:4 cis:trans diastereoselectivity. tert-Butyl spiroisoxazolinoprolinates were separable by column chromatography and amenable to scale-up leading to single diastereoisomers of N-Boc and N-Fmoc protected spiroisoxazolinoproline amino acids.
Cheng
Wei-Chieh
WC
Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616-5295, USA.
Liu
Yannan
Y
Wong
Melissa
M
Olmstead
Marilyn M
MM
Lam
Kit S
KS
Kurth
Mark J
MJ
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010080:Oxazoles; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D010080:Oxazoles; D011392:Proline