Total synthesis of natural dysidiolide.
Dysidiolide (1), a novel sesterterpenoid previously isolated from the Caribbean sponge Dysidea etheria de Laubenfels, inhibits the action of the protein phosphatase, cdc25A. The authors establish a novel total synthesis of natural dysidiolide (1) using intramolecular Diels-Alder reaction as the key step from optically active cyclohexenone 3. Decalin, the core structure of 1, was constructed by intramolecular Diels-Alder reaction of the diene ester generated by elimination of the phenyl sulfoxide group from sulfoxide ester 6 prepared from cyclohexenone 3. Diastereoselective methylation at C-7, alkylation at C-6, and deoxygenation of C-12 and C-24 positions gave the fully substituted bicyclic core of 1. The two side chains of the bicyclic core were further extended so as to afford natural dysidiolide (1). The total yield of this synthesis exceeds that of previous syntheses of 1.
Miyaoka
H
H
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Kajiwara
Y
Y
Hara
Y
Y
Yamada
Y
Y
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D011161:Porifera / Q000737:chemistry
C121906:dysidiolide; D015107:4-Butyrolactone