C-2 Dimethyl seco-Mevinic Acids. Synthesis of Monocyclic HMG-CoA Reductase Inhibitors from (R)-(-)-Carvone

Article abstract of DOI:10.1021/jo00052a031

An efficient preparation of novel monocyclic HMG-CoA reductase inhibitors from (R)-(-)-carvone is reported.Utilizing this chiral carbon pool, the C-2 dimethyl seco-mevinic acid 3a was prepared in 17 steps and 5.2percent overall yield.The key chiral intermediate aldehyde 10a was prepared via a short and efficient synthetic sequence (six steps, 27percent yield) from (R)-(-)-carvone.The appropriate chirality of the diol acid side chain was secured by employing the chiral acetate synthon "(S)-HYTRA" and by performing a stereoselective 1,3-syn reduction on the β-hydroxy ketone 19.Structural requirements at the C-2 position are rather stringent, and deletion of or addition of an extra methyl group are both unacceptable modifications for this novel class of monocyclic HMG-CoA reductase inhibitors.