Synthesis of Potential Mechanism-Based Inactivators of Lanosterol 14α-Methyl Demethylase

Article abstract of DOI:10.1021/jo00292a037

Lanosterol 14α-methyl demethylase is a key enzyme in the degradation of lanosterol to cholesterol.This cytochrome P-450 monooxygenase catalyzes the oxidative removal of the methyl group at C-14 of lanosterol.Inhibitors of this enzyme may prove useful as cholesterol-lowering agents and as antimycotics.This paper describes the design and synthesis of seven potential mechanism-based inactivators (compounds 9 - 15) of lanosterol 14α-methyl demethylase.The appropriately protected aldehydes 20a and 20b were the key intermediates in the synthesis of compounds 9,11,12,14,15.A method was developed for the homologation of these aldehydes to give 25a and 25b, which were converted to lanosterol analogues 10 and 13.