Synthesis of (+/-)- and (-)-vibralactone and vibralactone C.
Mander reductive alkylation of methyl 2-methoxybenzoate with prenyl bromide and hydrolysis of the enol ether afforded methyl 6-oxo-1-prenyl-2-cyclohexenecarboxylate. This was converted in five steps (reduction of the ketone, saponification, iodolactonization, ozonolysis, and intramolecular aldol reaction) to a spiro lactone cyclopentenal. An efficient first synthesis of (+/-)-vibralactone was completed by retro-iodolactonization with activated Zn, formation of the beta-lactone (vibralactone C), and reduction of the aldehyde. Except for the novel use of an iodolactone to protect both the prenyl double bond and carboxylic acid, no protecting groups were used. A similar sequence starting with asymmetric reductive alkylation of the (2S)-2-methoxymethoxymethylpyrrolidine amide of 2-methoxybenzoic acid with prenyl bromide afforded (-)-vibralactone confirming the absolute stereochemical assignment that was based on computational methods.
Zhou
Quan
Q
Department of Chemistry MS 015, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Snider
Barry B
BB
D000478:Alkylation; D062425:Hydroxybenzoate Ethers; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D012459:Salicylates / Q000737:chemistry; D013237:Stereoisomerism
D062425:Hydroxybenzoate Ethers; D007783:Lactones; D012459:Salicylates; C522315:vibralactone; C534371:vibralactone C; C081914:2-methoxybenzoic acid
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