Germacrene A–A Central Intermediate in Sesquiterpene Biosynthesis

Abstract

This review summarises known sesquiterpenes whose biosyntheses proceed through the intermediate germacrene A. First, the occurrencea nd biosynthesis of germacrene Ai nN ature and its peculiar chemistry will be highlighted , followed by ad iscussion of 6-6 and 5-7 bicyclic compounds and their more complex derivatives. For each compound the absolutec onfiguration, if it is known,a nd the reasoning for its assignment is presented. 2. Germacrene A 2.1. Occurrence in Nature (À)-Germacrene A(1,S cheme 2) was first isolated in 1970 from the gorgonian Eunicea mammosa. [7] Its absolute configuration was established as (S)-(À)-1 through its Cope rearrangement to (+ +)-b-elemene (2)f or which the configurational assignment was performed by chemical correlation of (À)-elemol(3)t o (À)-2. [8, 9] Compound (À)-1 is also believed to occur in the soft coral Lobophytum, [10] andi st he alarm pheromone of the aphid Terioaphis maculata. [11, 12] In the course of this work it was noticed that the optical rotation([ a] D 25 = À26.8, c 1.0, CCl 4)w as significantly highert han initially reported ([a] D 25 = À3.2, c 14.4, CCl 4), [7] which is explainableb yapartial rearrangement of purified (À)-1 to (+ +)-2,o ra lternatively, 1 isolated from E. mammosa was not enantiomerically pure. However,the opticalrotation of (+ +)-2 ([a] D 25 =+15.1, neat) reported in this initial study [7] matches the reported value for (À)-2 ([a] D 25 = À15.8, c 0.50, CHCl 3)o btainedb yC ope rearrangement of (+ +)-1, [13] thus disfa-Scheme1.Te rpene cyclisation modes for FPP. Scheme2.Structure of 1 and its absolute configurationbyc hemicalcorrelation.

Klyflaccilins B‐T, Polyoxgenated Eunicellins from the Soft Coral Klyxum flaccidum

“…Four eunicellins exhibited a C6=C7 double bond (Figure 2), including klyflaccilins B ( 1 ) and C ( 2 ). The observed line broadening in their 13 C‐NMR spectra is likely a result of a high ring strain in the medium‐sized 9‐membered ring C associated with slowly interconverting conformers, similar to the observations for germacrene A [15] . Large parts of the planar structures were determined by 2D‐NMR (Figure S1), and key HMBC correlations indicated the attachment of acetyl and butyryl groups at O12 and O13, respectively, for both compounds.…”

“…The observed line broadening in their 13 C-NMR spectra is likely a result of a high ring strain in the medium-sized 9-membered ring C associated with slowly interconverting conformers, similar to the observations for germacrene A. [15] Large parts of the planar structures were determined by 2D-NMR ( Figure S1), and key HMBC correlations indicated the attachment of acetyl and butyryl groups at O12 and O13, respectively, for both compounds. The only difference lies in the configuration of the C6=C7 double bond that is E-configured in 1 and Z-configured in 2, a rare feature in eunicellins, [16][17][18][19] as is evident from the H6-Me19 NOESY correlation.…”

“…The second butyryl group must be attached to a tertiary hydroxy group, and the downfield shift of C3 (δ = 84.29 ppm) suggested attachment at this position. The structure of 5 was confirmed by GaKα X-ray diffraction analysis which also gave access to the absolute configuration ( Figure 5, Flack parameter: À 0.02 (15)). The klyflaccilins G-N (6-13) are generally esterified at O4 showing acetate, butyrate, or 2-hydroxybutyrate groups, while compounds 11-13 showed additional esterifications (acetate or butyrate esters) at O6.…”

1,2‐ or 1,3‐Hydride Shifts: What Controls Guaiane Biosynthesis?

“…Germacrene A ( 1 ) and hedycaryol ( 2 ) belong to the most important intermediates of sesquiterpene biosynthesis and numerous compounds derive from them, [17] likely because their fairly strained ten‐membered ring is sufficiently reactive for further protonation induced cyclizations (Scheme 1 ).…”

The Sesquiterpene Synthase PtTPS5 Produces (1S,5S,7R,10R)-Guaia-4(15)-en-11-ol and (1S,7R,10R)-Guaia-4-en-11-ol in Oomycete-Infected Poplar Roots

“…A biosynthetic hypothesis for these sesquiterpene alcohols suggests formation proceeds by 1,10-cyclisation and capture with water to form hedycaryol ( Figure 2 B). Its reprotonation at C10 can initiate a second cyclisation, as frequently observed for germacrane-type sesquiterpenes [ 20 ], to give a guaiane skeleton, followed by deprotonations from C15 or C5 to yield guaia-4(15)-en-11-ol and guaia-4-en-11-ol, respectively. The absolute configuration of guaia-4(15)-en-11-ol was determined through chemical correlation using stereoselectively deuterated precursors.…”