Total Synthesis of (+)-Lactacystin

A total synthesis of the novel neurotrophic agent (+)-lactacystin ( 1 ) has been achieved in 11 steps and 14% overall yield from (2 R,3 S )-3-hydroxyleucine [(+)- 16 ]. The construction and bioassay of several active analogs are also described. A new asymmetric approach furnished the four stereoisomers of 3-hydroxyleucine, as required starting materials in high overall yield and enantiomeric purity.