Total synthesis of (+)-compactin by a double Michael protocol

Formal Enantioselective Synthesis of (+)-Compactin

“…This desilylation provided the targeted (+)-compactin diol 2a in 31% from the TMS substituted decalin 17a and in 36% yield from the BDMS-substituted decalin 17b . The characterization data for diol 2a proved to be identical with published information 2f 4 Ring closing metathesis …”

“…The discovery of (+)-compactin ( 1 ) and its ability to inhibit the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, which has a key role in endogeneous cholesterol biosynthesis, has led to the publication of several syntheses and the development of a therapeutic class of compounds (i.e., statins) that are currently used as cholesterol-lowering drugs.…”

Pharmaceuticals

“…Consequently, in the course of a few years a series of total syntheses was published. [385][386][387][388] Only one of these, which are without exception highly interesting and attractive syntheses, will be presented here. [389] The starting material for Hoffmann-La Roche's synthesis is (S)-pulegone, the stereogenic centre of which then determines in highly diastereoselective reactions all other stereocentres in the hexahydronaphthalene and lactone fragments.…”

Statine. Cholesterolsenker

“…Es ist nicht überraschend, dass Moleküle wie Mevastatin und Lovastatin schon kurz nach ihrer Entdeckung das ungeteilte Interesse vieler Naturstoffchemiker auf sich gezogen haben, worauf in der Folge eine Reihe von Totalsynthesen publiziert wurden [38][39][40][41]. Nur eine der durchweg hoch interessanten und reizvollen Synthesen soll hier vorgestellt werden (Abbildung 29) [42].…”