Codinaeopsin

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Codinaeopsin
Codinaeopsin.png
Names
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
Identifiers
3D model (JSmol)
ChemSpider
Properties
C31H38N2O3
Molar mass 486.66 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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 involves a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid.

Biosynthesis[edit]

Formation of linear polyketide[edit]

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]

Figure 1. Formation of linear polyketide


Formation of tetramic acid (2,4-pyrrolidinone)[edit]

L-Tryptophan is introduced by a nonribosomal peptide synthetase (NRPS) module and results in the central heterocyclic tetramic acid (2,4-pyrrolidinone). 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[edit]

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

Figure 2. Formation of tetramic acid and cyclization of PKS unit

References[edit]

  1. ^ a b c Kontnik, Renee; Clardy, Jon (2008). "Codinaeopsin, an Antimalarial Fungal Polyketide". Org. Lett. 10 (18): 4149–4151. doi:10.1021/ol801726k. 
  2. ^ Auclair, Karine; Sutherland, Andrew; Kennedy, Jonathan; Witter, David J.; Van den Heever, Johan P.; Hutchinson, C. Richard; Vederas, John C. (2000). "Lovastatin Nonaketide Synthase Catalyzes an Intramolecular Diels−Alder Reaction of a Substrate Analogue". Journal of the American Chemical Society. 122 (46): 11519–11520. ISSN 0002-7863. doi:10.1021/ja003216+.