Transannular Cyclization of (4<i>S</i>,5<i>S</i>)-Germacrone-4,5-epoxide under Basic Conditions to Yield Eudesmane-Type Sesquiterpenes

Abstract

Transannular cyclizations of germacrone-4,5-epoxide under acidic and thermal conditions have been reported in our previous study. However, this process gave the different and interesting results under basic conditions. (4S,5S)-Germacrone-4,5-epoxide (1) was treated under basic conditions to yield four products (2-5). Compound 2 was an isomer of 1 -(4S,5S,9Z)-4,5-epoxygermacra-7(11),9-dien-8-one-and the remaining three compounds (3-5) were eudesmane-type derivatives. Compounds 4 and 5 are new compounds. The structures of the new compounds were determined using high resolution (HR)-MS, one dimensional (1D)-NMR, 2D-NMR and circular dichroism (CD) spectroscopic data. Products 3-5 had the same carbon skeleton as that of eudesmane-type compounds; however, these compounds showed different arrangement of isoprene units to the natural eudesmane-type sesquiterpenes.

“Mirror-Image” Manipulation of Curdione Stereoisomer Scaffolds by Chemical and Biological Approaches: Development of a Sesquiterpenoid Library

“…Additionally, Kuroyanagi and co-workers also reported that the transannular cyclization of germacrene-type compounds might yield eudesmane-type sesquiterpenoids. 21 Although the spirolactone structure and potential bioactivity of curcumalactone (4a) have attracted significant interest, its challenging synthesis has been a major obstacle in exploring its promising chemistry and bioactivity. The first and only enantioselective total synthesis of curcumalactone was reported in 2012.…”

“…Moreover, curdione ( 1a ), 3α-hydroxycurdione ( 2a ), and 2β-hydroxycurdione ( 3a ) could be transformed into curcumalactone [(1 S ,4 S ,5 R ,7 S )-Cl, 4a ], 3α-hydroxycurcumalactone [3α-OH-(1 S ,4 S ,5 R ,7 S )-Cl, 5a ], and 2β-hydroxycurcumalactone [2β-OH-(1 S ,4 S ,5 R ,7 S )-Cl, 6a ] possessing a spirolactone skeleton formed via transannular cyclization, upon acid treatment (Figure ). Additionally, Kuroyanagi and co-workers also reported that the transannular cyclization of germacrene-type compounds might yield eudesmane-type sesquiterpenoids . Although the spirolactone structure and potential bioactivity of curcumalactone ( 4a ) have attracted significant interest, its challenging synthesis has been a major obstacle in exploring its promising chemistry and bioactivity.…”