Enantioselective synthesis of (2-pyridyl)alanines via catalytic hydrogenation and application to the synthesis of L-azatyrosine.
[reaction: see text] A novel method for the synthesis of (2-pyridyl)alanines 2a-b was developed by converting (2-pyridyl)dehydroamino acid derivatives 1a-b to the corresponding N-oxides 3a-b followed by asymmetric hydrogenation using (R,R)-[Rh(Et-DUPHOS)(COD)]BF(4) [(R,R)-6] catalyst and subsequent N-oxide reduction in 80-83% ee. This methodology was applied to the total synthesis of L-azatyrosine [(+)-12], an antitumor antibiotic, starting from (5-benzyloxy)-2-pyridylmethanol (7), in >96% enantiomeric purity.
Adamczyk
M
M
Department of Chemistry (9 NM), Building AP20, Diagnostics Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064-6016, USA. maciej.adamczyk@abbott.com
Akireddy
S R
SR
Reddy
R E
RE
D000409:Alanine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis*; D013237:Stereoisomerism
C115667:2-pyridyl alanine; D000903:Antibiotics, Antineoplastic; D011725:Pyridines; C011870:beta-(5-hydroxy-2-pyridyl)alanine; D006859:Hydrogen; D000409:Alanine