Asymmetric Total Synthesis and Formal Total Synthesis of the Antitumor Sesquiterpenoid (+)-Eremantholide A

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/orlef7/asap/abs/ol0700862.html

From: Prof. Karl J. Hale at University College London

(+)-Eremantholide A has pronounced antitumor effects against human KB nasopharyngeal carcinoma.

The synthesis is presented in a very detailed manner - you almost don't have to go to the SI section to look up details. The synthesis is ok over all - a little too linear. One serious setback at the end is the inability of the planned enantioselective deprotonation and subsequent alkylation to provide the desired diastereomer selectively. Using chiral lithium bases (lithium bis[(S)-1-alpha-methylbenzylamide] and lithium bis[(R)-1-alpha-methylbenzylamide]), they obtained the undesired enantiomer predominantly in both cases (undesired:desired = approx 2.3-2.5:1). In the end, they had to settle with KHMDS in toluene to achieve a 1:1 mixture of diastereomers. The key reaction in the end was RCM with Hoveyda-Grubb catalyst (54%).