Diastereo- and enantioselective synthesis of beta-hydroxy-alpha-amino acids: application to the synthesis of a key intermediate for lactacystin.
The development of a highly efficient and stereoselective methodology for the preparation of beta-hydroxy-alpha-amino acids is described. Nucleophilic addition of enolates of tricyclic iminolactones 1a and 1b to aldehydes in the presence of 6 equiv of lithium chloride in THF at -78 degrees C leads to aldol adducts in good yield (63-86%) and high diastereoselectivity (up to >25:1 dr). Subsequently, hydrolysis of the aldol adducts under acidic conditions leads to the corresponding beta-hydroxy-alpha-amino acids in good yields (up to 83%) and excellent enantiomeric excesses (99% ee) with good recovery yields of the chiral auxiliaries 6 and 7. This methodology was applied to the facile synthesis of the key intermediate for lactacystin along with several isomers.
Li
Qiong
Q
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PRC.
Yang
Shao-Bo
SB
Zhang
Zhihui
Z
Li
Lei
L
Xu
Peng-Fei
PF
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000447:Aldehydes / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D006868:Hydrolysis; D013237:Stereoisomerism; D013379:Substrate Specificity
D000447:Aldehydes; D000596:Amino Acids; C067713:lactacystin; C116609:3-hydroxybutanal; D000111:Acetylcysteine