Konrad Siegel

First Total Synthesis of Dihydroxerulin, a Potent Inhibitor of the Biosynthesis of Cholesterol

Dihydroxerulin (5) is a noncytotoxic inhibitor of cholesterol biosynthesis. In spite of being achiral and devoid of OH groups, it was synthesized efficiently in 2×5 steps in two linear sequences plus one terminating step, from the optically active, multiply hydroxylated L-gulonolactone via the key intermediates 1–4. 1H NMR spectroscopy revealed that the C8=C9 bond of synthetic and natural 5 is trans-substituted.

Stereoselective Syntheses of γ-Lactones and γ-Alkylidene- Butenolides

Five-membered ring lactones abound in nature and have ever since challenged synthetic chemists.1,3 They comprise butanolides (1), butenolides (2), α-alkylidenebutanolides (3), and γ-alkylidenebutenolides (4; Fig. 1). We have developed versatile routes to such compounds. They encompass only a few steps and ensure a high degree of stereocontrol at all stereogenic sp 3 centers and C=C bonds. In addition they allow to vary the substituents R, R′, and R″ considerably. Therefore, we were able to synthesize butanolides and butenolides which differed structurally from one another distinctly.