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Codinaeopsin

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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
CAS Number
3D model (JSmol)
ChEBI
ChemSpider
PubChem CID
CompTox Dashboard (EPA)
InChI
  • InChI=1S/C32H40N2O3/c1-7-19(3)26-21(5)14-31(6)13-18(2)12-20(4)28(31)27(26)29(35)24-16-32(37,34-30(24)36)15-22-17-33-25-11-9-8-10-23(22)25/h7-11,14,16-18,20,26-28,33,37H,12-13,15H2,1-6H3,(H,34,36)/b19-7+/t18-,20+,26-,27-,28+,31+,32?/m1/s1Key: FFIWOIAVVDGNHZ-ZQXRKGDHSA-N
SMILES
  • C/C=C(\C)/1(2(C(C2(C=C1C)C)C)C)C(=O)C3=CC(NC3=O)(CC4=CNC5=CC=CC=C54)O
Properties
Chemical formula C32H40N2O3
Molar mass 500.683 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). checkY verify (what is  ?) Infobox references
Chemical compound

Codinaeopsin is an antimalarial alkaloid isolated from a endophytic mold found in Vochysia trees 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. 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).

Figure 1. Formation of linear polyketide
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.

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.

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

References

  1. ^ Kontnik, Renee; Clardy, Jon (2008). "Codinaeopsin, an Antimalarial Fungal Polyketide". Org. Lett. 10 (18): 4149–4151. doi:10.1021/ol801726k. PMC 2626159. PMID 18698786.
  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. Bibcode:2000JAChS.12211519A. doi:10.1021/ja003216+. ISSN 0002-7863.
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