CONFORMATIONAL-ANALYSIS OF ISOLATED FORSK OLIN AND SOMES OF ITS PRECURSORS BY FORCE-FIELD CALCULATIONS

The conformational study of a molecule of isolated Forskolin, using mo lecular mechanics, shows that the more stable conformations have two i ntra-molecular H-bonds. One of these bonds lies between the hydrogen o f the 9alpha-hydroxy group and the oxygen of the 1alpha-hydroxy group, as in the crystalline state. The second H-bond is between the hydroge n atom of the 6beta-hydroxy group and the sp3 oxygen of the acetyl gro up. The molecule may be viewed as three main rings. The B-ring, a dist orted chair, is almost rigid. The A-ring is also a distorted chair, bu t may interconvert into a distorted twist-boat, although the 7.5 kcal/ mol energy barrier is a limiting factor. Finally, the C-ring may easil y interconvert into a chair conformation (with only 3.2 kcal/mol energ y barrier), which favors the rotational mobility of the vinyl group.