Costunolide

Costunolide
IUPAC name (3aS,6E,10E,11aR)-6,10-dimethyl-3-methylene-3,3a,4,5,8,9-hexahydrocyclodeca[b]furan-2(11aH)-one
Identifiers
CAS number	553-21-9 N
PubChem	5281437
ChemSpider	4444782 Y
UNII	4IK578SA7Z Y
MeSH	(+)-Costunolide
ChEBI	CHEBI:3900 Y
ChEMBL	CHEMBL205612 N
Jmol-3D images	Image 1
SMILES O=C/1O[C@@H]2/C=C(/CC/C=C(/CC[C@H]2C\1=C)C)C
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
Properties
Molecular formula	C15H20O2
Molar mass	232.318
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

(+)-Costunolide is a sesquiterpene lactone that 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 cyctochrome 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]

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

References

1. ^ ^{a b} 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. http://www.plantphysiol.org/cgi/content/full/125/4/1930?maxtoshow=&hits=10&RESULTFORMAT=&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=125&firstpage=1930&resourcetype=HWCIT. 
2. ^ ^{a b} 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. http://www.plantphysiol.org/cgi/content/full/125/4/1930?maxtoshow=&hits=10&RESULTFORMAT=&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=125&firstpage=1930&resourcetype=HWCIT.