Conformational study and enantioselective, regiospecific syntheses of novel aminoxy trans-proline analogues derived from an acylnitroso Diels-Alder cycloaddition.
The cis/trans isomerization of the proline amide bond has many implications in biological processes. The conformations of representative acylnitroso-derived proline analogues derived from cyclopentadiene were shown to exist exclusively as the E or trans conformation in CD2Cl2. The energetically favored conformations were determined using COSMO self-consistent reaction field calculations at the B3LYP/6-31G level of theory in addition to low temperature 1H NMR studies. The syntheses of the acylnitroso-derived peptides utilized two methods to selectively functionalize either of two chemically similar esters in the acylnitroso-derived amino acids. A novel transpeptidation of the amino acid that controlled the absolute stereochemistry in the acylnitroso Diels-Alder cycloaddition took advantage of an activated aminoxy amide linkage to control regiochemistry. Alternatively, an enantioselective and regiospecific enzymatic resolution of a racemic dimethyl ester provided a novel aminoxy acid.
Shireman
B T
BT
Department of Chemistry & Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, Indiana 46556-5670, USA.
Miller
M J
MJ
Jonas
M
M
Wiest
O
O
D000577:Amides / Q000737:chemistry; D003517:Cyclopentanes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009603:Nitroso Compounds / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D003517:Cyclopentanes; D009603:Nitroso Compounds; D010455:Peptides; D011392:Proline