Natural and Unnatural A‐seco Terpenes from Pulegone: Synthesis of Galbanic Acid and Marneral Revisited

Abstract

We describe herein an improved chiral‐pool strategy for assembling the core structure 3 (both antipodes) of various A‐seco terpenoids that have allowed us to prepare natural galbanic acid [(–)‐1] from (S)‐(–)‐pulegone [(–)‐2]. Furthermore, we were able to increase both the yield and step efficiency of the synthesis of marneral [(+)‐7] as well as to access higher homologues of ent‐galbanic acid [(+)‐4], ent‐secodrial [(+)‐5], and bis‐epi‐secochiliotrin (6) from (R)‐(+)‐pulegone [(+)‐2]. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Galbanic acid inhibits HIF-1α expression via EGFR/HIF-1α pathway in cancer cells

“…According to the obtained results (Table 2) and also comparing with the previous published data [44] the structure of galbanic acid; sesquiterpene cumarin suggested for compound 6 ( Figure. 1).…”

Synthesis, biosynthesis and biological activities of galbanic acid – A review

“…Two remaining steps were desilylation of OH group at C11 and addition of umbelliferone to form methyl galbanate (12). Methyl galbanate was then saponified with LiOH to obtain GA (Corbu et al, 2009).…”

“…Hence, Corbu et al (2009) revised their synthesis pathway ( Figure 6) using ethyl cyanoformate instead of ethyl chloroformate that effectively increased the yield of reaction from 40 to 80%. They also used microwave-assisted coupling of umbelliferone and 11 applying the Mitsunobu etherification condition, which again increased the yield of reaction from 6 to 28%.…”

Identification of marneral synthase, which is critical for growth and development in Arabidopsis

“…Manerol was synthesized as described by Corbu et al (2009). The common intermediate (a sesquiterpene) was prepared on a large scale using our chiral pool-based marnerol synthesis starting from plant-derived pulegone (a monoterpene).…”