Improved preparation of racemic 2-amino-3-(heteroaryl)propanoic acids and related compounds containing a furan or thiophene nucleus.
Racemic 2-amino-3-(heteroaryl)propanoic acids (1), mostly with a furan or thiophene nucleus as a heteroaryl group, were synthesized in 48-94% yield by the reduction of 3-(heteroaryl)-2-(hydroxyimino)propanoic acids (5) with zinc dust and formic acid in the presence of a catalytic amount of iron dust at 60 degrees C for 2 h. Under these conditions, unfavorable hydrogenolysis of bromine on the thiophene nucleus does not occur. Traditional N-formylation of the prepared 3-(heteroaryl)alanine (1) with a mixture of formic acid and acetic anhydride afforded 2-(formylamino)-3-(heteroaryl)propanoic acids (6) in 51-95% yield.
Kitagawa
Tokujiro
T
Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University, Nishi-ku, Kobe 651-2180, Japan. kitagawa@pharm.kobegakuin.ac.jp
Khandmaa
Dashrenchin
D
Fukumoto
Ayumi
A
Asada
Makoto
M
D000596:Amino Acids / Q000138:chemical synthesis*; D002384:Catalysis; D005561:Formates / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis; D007501:Iron / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011422:Propionates / Q000138:chemical synthesis*; D013876:Thiophenes / Q000138:chemical synthesis; D015032:Zinc / Q000737:chemistry
D000596:Amino Acids; D005561:Formates; D005663:Furans; D011422:Propionates; D013876:Thiophenes; C030544:formic acid; D007501:Iron; D015032:Zinc