Synthesis of (+)-Lactacystin

Significance

Wardrop and co-workers report a formal synthesis of the 20S proteasome inhibitor (+)-Lactacystin via a 1,5 C-H alkylidenecarbene insertion. The introduction of the quaternary ste­reocenter in the target molecule is a significant challenge and, with many previous syntheses relying on an aldol-type approach, novel strategies towards this and similar targets remain of the utmost importance. Hayes and co-workers have previously disclosed a similar approach to (+)-Lactacystin (Tetrahedron Lett. 2002, 43, 6609-6611) as part of a program directed towards the synthesis of a variety of 3-pyrrolines via 1,5 C-H alkylidenecarbene insertion (Org. Lett. 2001, 3, 3377-3379).