Spotted a new polyketide natural product last week, opaliferin:
Its isolation and structure determination were described by Umeyama and colleagues together with Grundiewska, from Poland, in a recent Organic Letters.
It is a secondary metabolite of an entomopathogenic fungus, that is one which grows on the body of an insect whose spores then bore down inside the insects body eventually killing it. The fungus belonging to the Cordyceps species are well known in Asian medicine. The secondary metabolites having a variety of interesting pharmacological activities on the hepatic, renal, cardiovascular, immunologic, and nervous systems, not to mention anticancer activity. The fungal strain producing this compound is NBRC 106954.
Our intrepid isolationists cultured this strain for 30 days in a medium containing sucrose, agar, water and the filtrate from boiled potatoes! This must be a standard method and presumably something which the fungus likes is extracted into the boiling water, perhaps someone can shed light on what this could be? Anyway after extraction with methanol the 47g of residue was extracted with ethyl acetate and n-butanol. Chromatography of the ethyl acetate extract gave 10 fractions. Fraction 6 (72 mg) was re-chromatographed to give 23 mg of opaliferin. This is actually quite a large quantity.
The various NMR experiments provided the connectivities through the molecule and to finally nail the structure an x-ray was obtained from the bis(para-bromobenzoyl) derivative.
A biosynthetic pathway of this compound was also suggested involving a rather clever spiro-cyclisation from the intermediate shown below:
Opaliferin was evaluated for biological activity and proved inactive against trypanosomes and was not an anti-malarial compound. It did show some weak cytotoxicity against 3 different cell lines.
This is only the second example of a natural product containing this structural unit, a tetrahydrofuran connected to a cyclopentanone by an external double bond. The other reports appearing some time ago (early seventies). Congratulations of the isolation and structure determination.
So get synthesising, this compound looks simple but will be challenging to make.
5,027 total views, 3 views today
