Costunolide

Costunolide

Names
Preferred IUPAC name (3aS,6E,10E,11aR)-6,10-Dimethyl-3-methylidene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2(3H)-one
Identifiers
CAS Number	553-21-9^Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:3900^Y
ChEMBL	ChEMBL205612^N
ChemSpider	4444782^Y
ECHA InfoCard	100.208.663
MeSH	(+)-Costunolide
PubChem CID	5281437
UNII	4IK578SA7Z^Y
CompTox Dashboard (EPA)	DTXSID001029520
InChI InChI=1S/C15H20O2/c1-10-5-4-6-11(2)9-14-13(8-7-10)12(3)15(16)17-14/h5,9,13-14H,3-4,6-8H2,1-2H3/b10-5+,11-9+/t13-,14+/m0/s1^Y Key: RYLQFBHBWLLLL-AHNJNIBGSA-N^N
SMILES O=C/1O[C@@H]2/C=C(/CC/C=C(/CC[C@H]2C\1=C)C)C
Properties
Chemical formula	C15H20O2
Molar mass	232.323 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

(+)-Costunolide is a naturally occurring sesquiterpene lactone, first isolated in Saussurea costus roots in 1960.[1] It is also found in lettuce.[1]

Synthesis

It is synthesized through the mevalonate pathway, seen in Figure 1. The synthesis begins with the cyclization of compound 1, farnesyl pyrophosphate (FPP), which is mediated by a sesquiterpene cyclase, (+)-germacrene A synthase, to form compound 2, (+)-germacryl cation.[1] Inside this same enzyme, a proton is lost to form 3, (+)-germacrene A.[2] The isoprenyl side chain of (+)-germacrene A is then hydroxylated by (+)-germacrene A hydroxylase, which is a cytochrome P450 enzyme, to form 4.[1] NAD(P)^+ dependent hydrogenase(s) then oxidize 4, germacra-1(10),4,11(13)-trien-12-ol, through the intermediate 5, germacra-1(10),4,11(13)-trien-12-al to form compound 6, germacrene acid. The cytochrome P450 enzyme, (+)-costunolide synthase, which is a NADPH and O₂ dependent enzyme, then oxidizes germacrene acid to give the alcohol intermediate, 7, which then cyclizes to form the lactone 8, (+)-costunolide.[3]

Biosynthesis of (+)-Costunolide.

Figure 1. Biosynthesis of (+)-Costunolide.[2]

References

1. Kraker, J.; Franssen, M.; Dalm, M.; Groot, A.; Bouwmeester, H. (April 2001). "Biosynthesis of Germacrene A Carboxylic Acid in Chicory Roots. Demonstration of a Cytochrome P450 (+)-Germacrene A Hydroxylase and NADP+-Dependent Sesquiterpenoid Dehydrogenase(s) Involved in Sesquiterpene Lactone Biosynthesis". Plant Physiology. 125 (4): 1930–1940. doi:10.1104/pp.125.4.1930. PMC 88848. PMID 11299372.
2. Dewick, Paul M. (2009). Medicinal Natural Products: A Biosynthetic Approach. West Sussex, United Kingdom: John Wiley & Sons Ltd. p. 214.
3. Kraker, J.; Franssen, M.; Joerink, M.; Groot, A.; Bouwmeester, H. (April 2002). "Biosynthesis of Costunolide, Dihydrocostunolide, and Leucodin. Demonstration of Cytochrome P450-Catalyzed Formation of the Lactone Ring Present in Sesquiterpene Lactones of Chicory". Plant Physiology. 129: 257–258. doi:10.1104/pp.010957. PMC 155889. PMID 12011356.