FIRST TOTAL SYNTHESIS OF DIHYDROXERULIN, A POTENT INHIBITOR OF THE BIOSYNTHESIS OF CHOLESTEROL

Dihydroxerulin (1) is a noncytotoxic inhibitor of cholesterol biosynth esis. In spite of being achiral and devoid of OH groups, it was synthe sized efficiently (12 steps, 6 steps in the longest linear sequence) f rom the optically active, polyhydroxylated sugar lactone 6. Our synthe sis follows the strategy of Scheme 2 and illustrates with the beta-eli mination 10-->(Z)-9 a novel general approach to gamma-alkylidenebuteno lides with stereopure C-beta=C bonds. The enol triflate (Z)-9 was hydr ogenolyzed to lactone (Z)-11 under very mild conditions. A Wittig reac tion with the derived aldehyde (2)-13 delivered 30% of the title compo und. Its 800 MHz H-1 NMR spectrum revealed that the C-8=C-9 bond of sy nthetic, and therefore also natural, 1 is trans-substituted.