A stereoselective total synthesis of the diterpene antitumor antibiotic myrocin C

The first total synthesis of racemic myrocin C has been achieved. This unique pentacyclic pimarane diterpene contains a cyclopropylcarbinyl tertiary allylic alcohol, as well as a tertiary ;A revised route was investigated where an endo-selective intermolecular Diels-Alder reaction was utilized. A highly functionalized tricyclic compound was produced which contained three of the seven asymmetric centers present in myrocin C. Attempts to introduce the cyclopropane by intramolecular alkylation of a variety of substrates were unsuccessful. However, upon further examination, cyclopropane installation was achieved via a novel organolithium-initiated cyclization of a homoallylic dienyl mesylate. This key reaction also liberated the necessary functionality for annulation of the final ring through an intramolecular Diels-Alder reaction to produce the pimarane diterpene skeleton. Stereoselective introduction of the two tertiary alcohols provided myrocin C.;A study of the bioactivation mechanism of myrocin C revealed that bisalkylation occurred upon addition of an organic nucleophile. Similar experiments on 6-desoxymyrocin C yielded a monoalkylated compound.