Codinaeopsin

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.

Codinaeopsin
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 486.656 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

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]

Figure 1. Formation of linear polyketide

Formation of tetramic acid (2,4-pyrrolidinone)

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

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
gollark: Yes, this is I believe around the lifespan of worker bees in winter.
gollark: > However, worker bees that are born before winter will live 4 to 6 months. Their main job over winter is to keep the queen warm. They take turns being on the outer edge of the cluster where it is cooler, and circulate back towards the center where it is warmer.This might be where you got it from?
gollark: I see.
gollark: <@102038103463567360> The sources I can find on honey bee lifespans say it's only 6ish weeks.
gollark: @ubq323 how is progress with the apioformic rewrite?

References
  1. Kontnik, Renee; Clardy, Jon (2008). "Codinaeopsin, an Antimalarial Fungal Polyketide". Org. Lett. 10 (18): 4149–4151. doi:10.1021/ol801726k. PMC 2626159.
  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. doi:10.1021/ja003216+. ISSN 0002-7863.
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