Stereoselective preparation of (E,E)-diene was accomplished by addition of trans-crotyl phenyl sulfone anion, followed by quenching with Ac2O and subsequent reductive elimination of sulfone acetate. Condensation of this with lithium anion of dimethyl methylphosphonate gave compound 1. Compound 2 was synthesized as shown in the scheme in the synthetic procedure. Compounds 1 and 2 were then combined using 1.3 eq sodium hydride in THF followed by reflux in chlorobenzene for 82 hr under nitrogen to get the enone 3. Simple organic reactions were used to get to lovastatin as shown in the scheme. Society and culture
Natural sources
Lovastatin is a naturally occurring compound found in low concentrations in food such as oyster mushrooms, red yeast rice, and Pu-erh. Brand names
Mevacor, Advicor (as a combination with niacin), Altocor, Altoprev

Other applications
In plant physiology, lovastatin has occasionally been used as inhibitor of cytokinin biosynthesis. See also
Medicinal fungi

References
External links
 Media related to Lovastatin at Wikimedia Commons

"Lovastatin". Drug Information Portal. U.S. National Library of Medicine.
Diarrhoea grade 2 or higher was found in 24% of these patients, thrombocytopenia grade 3 or higher in 28%, and fatigue grade 2 or higher in 26%. Interactions
The drug has a low potential for interactions via cytochrome P450 (CYP) liver enzymes and transporter proteins. The only relevant finding in studies was a reduction of ixazomib blood levels when combined with the strong CYP3A4 inducer rifampicin. The Cmax was reduced by 54% and the area under the curve by 74% in this study. Pharmacology
Mechanism of action
At therapeutic concentrations, ixazomib selectively and reversibly inhibits the protein proteasome subunit beta type-5 (PSMB5) with a dissociation half-life of 18 minutes. This mechanism is the same as of bortezomib, which has a much longer dissociation half-life of 110 minutes; the related drug carfilzomib, by contrast, blocks PSMB5 irreversibly. Proteasome subunits beta type-1 and type-2 are only inhibited at high concentrations reached in cell culture models.PSMB5 is part of the 20S proteasome complex and has enzymatic activity similar to chymotrypsin. It induces apoptosis, a type of programmed cell death, in various cancer cell lines. A synergistic effect of ixazomib and lenalidomide has been found in a large number of myeloma cell lines. Pharmacokinetics
The medication is taken orally as a prodrug, ixazomib citrate, which is a boronic ester; this ester rapidly hydrolyzes under physiological conditions to its biologically active form, ixazomib, a boronic acid. Absolute bioavailability is 58%, and highest blood plasma concentrations of ixazomib are reached after one hour.