Codinaeopsin

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)	Interactive image;
ChemSpider	59650731;
PubChem CID	102412273;
	InChI InChI=1S/C31H40N2O3/c1-6-19(3)22-11-12-30(5)14-18(2)13-20(4)27(30)26(22)28(34)24-16-31(36,33-29(24)35)15-21-17-32-25-10-8-7-9-23(21)25/h6-10,16-18,20,22,26-27,32,36H,11-15H2,1-5H3,(H,33,35)/b19-6+/t18-,20+,22+,26-,27+,30-,31?/m1/s1 Key: VPTNOPBZJRGCMA-JCYPASGKSA-N;
	SMILES C/C=C(\C)/[C@@H]1CC[C@@]2(C[C@@H](C[C@@H]([C@H]2[C@@H]1C(=O)C3=CC(NC3=O)(Cc4c[nH]c5c4cccc5)O)C)C)C;
Properties
Chemical formula	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

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

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

References

Kontnik, Renee; Clardy, Jon (2008). "Codinaeopsin, an Antimalarial Fungal Polyketide". Org. Lett. 10 (18): 4149–4151. doi:10.1021/ol801726k. PMC 2626159.
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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[Isolation-1] Kontnik, Renee; Clardy, Jon (2008). "Codinaeopsin, an Antimalarial Fungal Polyketide". Org. Lett. 10 (18): 4149–4151. doi:10.1021/ol801726k. PMC 2626159.

[AuclairSutherland2000-2] 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.