Asymmetric total synthesis of halicholactone.
The asymmetric total synthesis of the marine metabolite, halicholactone 1, is described. The bisallylic triol 6 with three chiral centers at C8, C12, and C15 was constructed by [2,3]-sigmatropic rearrangement of the sulfoxide 18, which was prepared stereoselectively using the chirality of (diene)Fe(CO)3 complexes. Introduction of the trans-substituted cyclopropane subunit into 21 was successfully achieved using the modified regio- and stereoselective Simmons-Smith reaction. The use of RCM (ring-closing metathesis) methodology (4-->35) was pivotal for the formation of a nine-membered unsaturated lactone fragment of halicholactone 1. As this approach is flexible and stereoselective, other oxylipins could be synthesized by the protocol described herein.
Baba
Y
Y
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Saha
G
G
Nakao
S
S
Iwata
C
C
Tanaka
T
T
Ibuka
T
T
Ohishi
H
H
Takemoto
Y
Y
D000818:Animals; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis*; D011161:Porifera / Q000737:chemistry*
D007202:Indicators and Reagents; D007783:Lactones; D016859:Lipoxygenase Inhibitors; C431666:halicholactone