Total synthesis and determination of the absolute configuration of coscinosulfate. A new selective inhibitor of Cdc25 protein phosphatase.
The first total synthesis of coscinosulfate 1, a metabolite isolated from a sea sponge, starting from (+)-sclareolide 3 is described. The convergent synthesis strategy relies on the coupling of sulfone 21 with the bromide 26. The sulfone fragment 21 was obtained by successive asymmetric aldol reaction with aldehyde 2 to introduce the stereocenters at C-12 and C-13, followed by one-carbon homologation via Horner-Wadsworth-Emmons olefination. The selective sulfatation at C-12 was accomplished through the quinone intermediate 31 obtained by selective oxidation of hydroquinone 30; this, when followed by reduction, furnished the desired coscinosulfate 1. X-ray analysis of the intermediate aldehyde 18 confirmed the proposed structure.
Poigny
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Laboratoire de Chimie des Substances Naturelles, associé au CNRS, Muséum National d'Histoire Naturelle, 63, rue Buffon, F-75005 Paris, France.
Nouri
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Chiaroni
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A
Guyot
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M
Samadi
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M
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry; D054830:Sesterterpenes; D013237:Stereoisomerism; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
D000935:Antifungal Agents; D004224:Diterpenes; D004791:Enzyme Inhibitors; D054830:Sesterterpenes; D013729:Terpenes; C449079:coscinosulfate; C109395:sclareolide; D020687:cdc25 Phosphatases