Synthetic studies in the mevinoid field. The total synthesis of ML236A

catalyzed cyclocondensation of an aldehyde with an appropriate diene affords a new route to the title series. BACKGROUND AND PURPOSE OF THE INVESTIGATION The discovery of the mevinoids, the recognition of their ability to sharply lower the levels of serum cholesterol and the identification of their mode of action via their inhibition of the enzyme HMG CoA reductase, have been important in cardiovascular medicine (ref. 1, 2). Since the formation of mevalonate from 3-hydroxy-3-methylglutarate is apparently the limiting step in the mammalian biosynthesis of cholesterol (ref. 3) , the inhibition of this enzyme is a particularly inviting target for medical intervention. The studies described herein were formulated not only to reach these compounds, but were seen to have broad applications toward other important targets. After favorable demonstrations in model systems, it was then appropriate to demonstrate the scope of our findings via a total synthesis of the mevinoids (ref. 4). The second inducement was the opportunity to learn more about the structura