Study On The Total Synthesis Of Przewalskin B

Przewalskin B, a novel diterpenoid, possesses a unique tetracyclic skeleton that contains a spirocyclic enone system and a-hydroxy-p-ketone lactone moiety. We envisioned that przewalskin B would derive from icetexane diterpene and proposed the biogenetic pathway. The a-hydroxy-β-ketone lactone moiety would be furnished from the6,6-sprio structure via a benzilic acid rearrangement.Scheme1Proposed Biogenetic patheway of Przewalskin BIn the first, we performed the model study. a-Hydroxy of45was oxidized selectively by Cu(OAc)2, followed by immediate benzilic acid rearrangement in one pot, to give a, β-dihydroxy ester46and47.Scheme2Model StudyAccording to the model study, we attempted to contruct the precursor of benzilic acid rearrangement. The trials of Robinson annulations, alkylative dearomatization of p-phenol, Diels-Alder cycloaddition and intramolecular alkylation to generate the6,6-sprio ring was all failed. We successfully synthesized the precursor of rearrangement via NHK reaction, but aromatization was occurred in the benzilic acid rearrangement. Scheme3Total Synthesis of Przewalskin BAfter those experiments, we decided to change the strategy. We envisioned that the spiro-quaternary center would be established by Claisen rearrangement and the cyclopentenone ring would be contructed by RCM. Followed the plan, we eventually accomplished the synthesis of przewalskin B in12steps from the known compound48’.