A Three‐Step Synthesis of the Guaianolide Ring System

Abstract

By using a gallium(III) triflate catalyzed intramolecular (4+3) cycloaddition, a few functionalized furan‐derived tricycles that share the common guaianolide sesquiterpene ring system were prepared in a stereoselective manner in only three steps from commercially available starting materials. A discussion of the formation of alternative products is included, with possible substrate requirements to achieve the key cycloaddition step in an efficient way.

Kauniolide synthase is a P450 with unusual hydroxylation and cyclization-elimination activity

“…Previously, it was shown that feverfew P450s acting on germacrene A, germacrene A acid, costunolide and parthenolide all belong to the CYP71 family 11 – 14 , 18 . Moreover, the genes encoding the enzymes of the parthenolide biosynthesis pathway ( TpGAS 13 , TpGAO 13 , TpCOS 13 and TpPTS 19 ) show a distinct expression profile during feverfew ovary development, matching with the accumulation profile of parthenolide 11 , 13 , 14 (Supplementary Fig. 1a ).…”

“…1a ). The costunolide 3β-hydroxylase 19 , though, displays a slightly different expression profile (Supplementary Fig. 1a and 1b ).…”

“…The detection of sesquiterpene lactones with an exocyclic double bond in LC-Orbitrap-FTMS can sometimes be improved by conjugation to glutathione or cysteine 13 . This conjugation occurs non-enzymatically, is irreversible and in case of cysteine adds an exact mass of [M] = 121.01464 and results in a shorter retention time (RT) 19 . The reaction product of the enzyme encoded by Tp8879 using costunolide as substrate was therefore incubated with cysteine.…”

Trends in the Synthesis and Functionalization of Guaianolides

“…A very recent strategy was presented by Winne et al, [71] who assembled the guaianolide ring system in three straightforward synthetic operations by using a highly diastereoselective intramolecular [4+3] cycloaddition reaction of a catalytically generated furfuryl cation intermediate. The first precursor was generated in two steps by treating the anion derived from furan β-keto ester 176 with bromodiene 175.…”

“…This key step has been reported for the synthesis of promising products such as seco-guaianolides and dimeric guaianolides. [71] Other useful synthetic methodologies such as MARDi cascade, transition-metal catalysis, or ring-closing metathesis have also been introduced.…”