A New Stereocontrolled Synthesis of Dihydroxerulin, a Potent Noncytotoxic Inhibitor of the Biosynthesis of Cholesterol

Dihydroxerulin, 1, has been stereoselectively synthesized by a convergent approach in which a key step was the Wittig reaction between (Z)-5-[(E)-3-formyl-2-propenylidene]-5H-furan-2-one, 15, and the phosphonium ylid which derived from [(E)-2-decen-4,6-diyn-1-yl]triphenylphosphonium bromide, 19. Compound 19 was conveniently prepared by a short reaction sequence involving a Stille reaction between 1-trimethylstannyl-1,3-heptadiyne, 17, and (E)-3-iodo-2-propen-1-ol, 18. On the other hand, compound 15 was prepared in eight steps by a reaction sequence in which an immediate precursor to this butenolide, i.e. (Z)-5-[(2E)-4-hydroxy-2-butenylidene]-5H-furan-2-one, 34, was regio- and stereoselectively synthesized by Ag(I)-catalysed lactonization of the corresponding (Z)-2-en-4-ynoic acid. The structure and stereochemistry of 1 were established on the basis of its 1H and 13C NMR spectra at 600 and 150 MHz, respectively, and by a combination of 2D NMR techniques.