Codinaeopsin

Codinaeopsin
IUPAC name 5-((1H-indol-3-yl)methyl)-3-((1R,2R,4aS,6R,8S,8aS)-2-((E)-but-2-en-2-yl)-4a,6,8-trimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalene-1-carbonyl)-5-hydroxy-1H-pyrrol-2(5'H)-one
Properties
Molecular formula	C31H38N2O3
Molar mass	486.65 g mol−1
Y (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

Codinaeopsin is an antimalarial isolated from a fungal isolate found in white yemeri trees (Vochysia guatemalensis) in Costa Rica. It is reported to have bioactivity against Plasmodium falciparum with an IC₅₀ = 2.3 µg/mL (4.7 µM). Pure codinaeopsin was reported to be isolated with a total yield of 18 mg/mL from cultured fungus.^[1] The biosynthesis of codinaeopsin is manufactured by a polyketide synthase- nonribosomal peptide synthetase (PKS-NRPS) hybrid.

Biosynthesis

Formation of linear polyketide

The first step of the biosynthesis of codinaeopsin involves the assembly of the a linear polyketide by use of seven modules and incorporation of six methylmalonyl CoAs and one malonyl CoA by polyketide synthases (type I PKSs).^[1]

Formation of tetramic acid (2,4-pyrrolidindione)

L-Tryptophan is introduced by a nonribosomal peptide synthetase (NRPS) module and results in the central heterocyclic tetramic acid (2,4-pyrrolidindione). The formal oxidation-reduction is found to be achieved by a series of tautomeric shifts involving enol and imine intermediates in the ring and consistent by discovery both C-2’ epimers.^[1]

Cyclization of PKS-assembled unit

The PKS unit is hypothesized to cyclize by a Diels-Alder-like addition similar to other natural products such as lovastatin and solanapyrone.^[2]

References

1. ^ ^{a b c} Kotinik, Renee; Clardy, Jon (2008). "Codinaeopsin, an Antimalarial Fungal Polyketide". Org. Lett. 10 (18): 4149–4151. doi:10.1021/ol801726k. 
2. ^ Auclair, K.; Sutherland, A.; Kennedy, J.; Witter, D. J.; Van den Heever, J. P.; Hutchinson, C. R.; Vederas, J. C. (2000). J. Chem. Soc. 122: 11519. doi:10.1021/ja003216+.