Stereoselective synthesis of beta-benzyl-alpha-alkyl-beta-amino acids from L-aspartic acid.
A stereoselective synthesis of beta-benzyl-alpha-alkyl-beta-amino acids 1 and 2 from L-aspartic acid 3 has been developed. Methyl 5-phenyloxazolidin-2-one-4-acetate 4 was prepared from L-aspartic acid 3 through the acylation of benzene or phenyllithium with alpha-amino carboxyl group of L-aspartic acid skeleton. Alkylation of a dianion of 4 with alkyl halides and subsequent hydrogenation afforded anti-disubstituted beta-amino acids 1b and 1c in high stereoselectivities. Complete reversal of the stereoselection was realized by the alkylation of 4-phenyl-3-tert-butoxycarbonylamino-4-butanolide 6 which was obtained in a single step from 4. The 2,3,4-trisubstituted amino lactone 7 thus obtained was hydrogenated to give a syn-disubstituted beta-amino acid 2a. The syn-products 2b, 2c, and 2dwere alternatively prepared via aldol condensation of 6 with aromatic or aliphatic aldehydes followed by stereoselective reduction of the double bond with nickel chloride-sodium borohydride.
Seki
M
M
Product & Technology Development Laboratory, Tanabe Seiyaku Co., Ltd. , 3-16-89, Kashima, Yodogawa-ku, Osaka 532-8505, Japan.
Shimizu
T
T
Matsumoto
K
K
D000215:Acylation; D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006865:Hydrogenation; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
D000596:Amino Acids; D001593:Benzyl Compounds; D001224:Aspartic Acid