An optimized, convergent, safe synthesis of LAF389 (
9), an anti-cancer agent analogous to bengamide B, is described. Startingfrom <
IMG SRC="/images/gifchars/alpha.gif" BORDER=0>-
D-glucoheptonic (
D-glycero-
D-gulo-heptonic acid)
![](/images/gifchars/gamma.gif)
-lactone (
10), the lactone
15 was constructed in five steps. Majorimprovements were made in the preparation of the aldehydeprecursor
14 and subsequent olefination to yield
15 via amodified Julia protocol. This olefination was significantlyimproved by using TMSCl as an additive. The second fragmentof the drug substance,
![](/images/gifchars/epsilon.gif)
-caprolactam
7, was obtained in two
one-pot operations from (5
R)-5-hydroxy-
L-lysine (
1). Finally,opening
15 with
7 using sodium 2-ethyl hexanoate (Na-EH) gave
8, which on deprotection yielded LAF389.