New Formal Syntheses of Laurencione, a Labile Dihydrofuranone Derivative from the Red Alga Laurencia spectabilis

Abstract

A straightforward formal synthesis of the marine natural products laurencione was developed, utilizing elaboration of 5-acetoxy-3-chloropentan-2-one as the starting compound. The synthetic route consisted of (i) α-sulfenylation, (ii) α-chlorination of the resulting β-oxo sulfide, (iii) Hg2+-catalyzed methanolysis, (iv) methanolysis of the γ-acetoxy-α,α-dimethoxy ketone with subsequent cyclization and (v) acid hydrolysis of the acetal. Alternatively, laurencione was prepared from 1,1-dichloroacetone by a sequence of reactions involving (i) imination, (ii) regiospecific β-hydroxyethylation, (iii) hydrolysis, (iv) base-induced rearrangement of the resulting functionalized tetrahydrofuran and (v) final acid hydrolysis of laurencione methyl ether.