Diastereo- and Enantioselective Synthesis of β-Hydroxy-α-Amino Acids: Application to the Synthesis of a Key Intermediate for Lactacystin
Qiong Li
Shao-Bo Yang
Zhihui Zhang
Lei Li
Peng-Fei Xu
10.1021/jo8023973.s001
https://acs.figshare.com/articles/journal_contribution/Diastereo_and_Enantioselective_Synthesis_of_Hydroxy_Amino_Acids_Application_to_the_Synthesis_of_a_Key_Intermediate_for_Lactacystin/2876989
The development of a highly efficient and stereoselective methodology for the preparation of β-hydroxy-α-amino acids is described. Nucleophilic addition of enolates of tricyclic iminolactones <b>1a</b> and <b>1b</b> to aldehydes in the presence of 6 equiv of lithium chloride in THF at −78 °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 β-hydroxy-α-amino acids in good yields (up to 83%) and excellent enantiomeric excesses (99% ee) with good recovery yields of the chiral auxiliaries <b>6</b> and <b>7</b>. This methodology was applied to the facile synthesis of the key intermediate for lactacystin along with several isomers.
2009-02-20 00:00:00
Enantioselective
Diastereo
stereoselective
excess
diastereoselectivity
Application
Intermediate
acid
lithium
enolate
hydrolysis
Lactacystin
lactacystin
recovery
dr
presence
methodology
enantiomeric
equiv
chloride
Synthesi
Nucleophilic
aldehyde
7.
ee
acidic
THF
aldol adducts
Hydroxy
auxiliary
tricyclic iminolactones 1
chiral auxiliaries 6
yield
preparation
isomers
synthesis
Acid
hydroxy