Enantiospecific Synthesis of the Cubitane Skeleton

Abstract

The fully substituted 12-membered macrocycle of the cubitane-type diterpenoids has been assembled in an enantioselective manner following a novel "bridge-and-cut" strategy. Hydroxyalkylation of (S)-carvone afforded a carvonylgeraniol, which underwent transannular cyclization on treatment with samarium diiodide in THF. Fragmentation of one of the shorter bridges of the resulting [8.2.2]bicycle liberated the 12-membered ring with the desired cis-arrangement of the isopropenyl side chains.

Hydroxy-fipronil is a new urinary biomarker of exposure to fipronil

“…The pyrazole moiety of fipronil detrifluoromethylsulfinyl has a high degree of similarity with enols of β-ketocarbonyl compounds (Fig.2). Keeping in mind that enols and enolates are very reactive toward molecular oxygen and undergo addition reactions with it at ambient temperature (Cubbon and Hewlett 1968; Schottner et al 2010; Wang et al 2011) yielding α-hydroperoxy carbonyl compounds, a natural question arose: is a similar reaction possible for the appropriately substituted heterocycles and in particular for the pyrazole moiety of fipronil detrifluoromethylsulfinyl? Unfortunately, treatment of ( 1) with sodium hydroxide in methanol in the presence of ambient air only resulted in formation of the imidate ( 6) but not the desired peroxide.…”

Recent Advances of Total Syntheses of Diterpenoids Starting from Carvone

“…Scheme 8: Synthesis of cubitane core 97 by Lindel et al [19] Cyrneine A (110), isolated from the mushroom Sarcodon cyrneus, enhances neurite outgrowth in pheochromocytoma cells. In this total synthesis, after leading dihydrocarvone (90) to a 5-6-6 tricyclic ring system 107 by the intramolecular Heck reaction, a 5-6-7cyrneine framework was obtained by a carbenoid ring expansion [20] (Scheme 9).…”

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

“…The presumed organosamarium intermediate showed high preference for 1,4-addition, possibly due to the intramolecular nature of this transformation. 205 After having cleverly used the six-membered ring of carvone to template assembly of the bicyclo[8.2.2] tetradecane ring system, the authors then proceeded to dismantle it as cubitene possesses a single ring. Thus aerobic α-oxidation of ketone 161 (LHMDS, O 2 , P(OEt) 3 ) followed by carbonyl reduction afforded diol 162 which could be oxidatively cleaved in the presence of H 5 IO 6 /EtOH.…”