Comparison of balanol from Verticillium balanoides and ophiocordin from Cordyceps ophioglossoides.

Abstract

Recently, we reported the isolation of the potent protein kinase C inhibitor balanol (1) from the fungus Verticillium balanoides.In an earlier study, Konig et al. reported the isolation of ophiocordin (3), a structural isomer of 1, from the fungus Cordyceps ophioglossoides. The present study was designed to clarify whether or not balanol and ophiocordin are different compounds. The results indicated that the two fungi produced the same compound, the structure being that assigned to balanol. In addition, a thirty-fold increase in the production of balanol from V. balanoides was observed whenthe culture mediumwas changed from cornmeal/tomato paste to soy meal/glycerol.In our search for protein kinase C (PKC) inhibitors from microbial sources, we recently disclosed the isolation and structure elucidation of the potent inhibitor balanol (1) from the fungus Verticillium balanoides.^Balanol represents a novel class of PKCinhibitors and is the most potent inhibitor reported since the discovery of staurosporine.2~4) HumanPKCenzymes a, /ft, /ftl, y, <5, e, and y\ were inhibited by 1 with IC50 values of 4~9nM. The structure of balanol was unambiguously determined by ID and 2D NMRdata and chemical degradation. The absolute stereochemistry of 1 was assigned by X-ray diffraction of a /rara-bromobenzoyl derivative of 2.1} Very recently, the structure of balanol was confirmed by total

Total Synthesis of (−)‐Balanol, All Stereoisomers, Their N‐Tosyl Analogues, and Fully Protected Ophiocordin: An Easy Route to Hexahydroazepine Cores from Garner Aldehydes

“…IR spectra were recorded on a Perkin-Elmer RXI FT-IR spectrometer. 1 13 C NMR. All spectra were recorded at 25 8C.…”

“…Some PKC inhibitors are currently in clinical trials for various types of cancer. [8][9][10] Balanol (1 a), an unusual metabolite isolated by Kulanthaivel et al [11][12][13] from the fungus Verticillium balanoides collected from Pinus palustris needle litter in 1993, and later by Ohshima et al from Fusarium merismoids in 1994, [12] inhibits almost all PKC isoforms in the 4-5 nanomolar range. Ophiocordin (3), [14,15] a regioisomer of (À)-balanol (1 a), was isolated from Cordyceps ophioglossoides in 1977 and serves as an antibiotic with antifungal activity.…”

Crystal Structure of the Potent Natural Product Inhibitor Balanol in Complex with the Catalytic Subunit of cAMP-Dependent Protein Kinase

“…Balanol, an ATP mimetic and one of the most potent natural product protein kinase inhibitors discovered to date, is one such template particularly amenable to analogue design. The isolation of balanol ( Figure 1) may have been reported initially with the name of ophiocordin, an antifungal metabolite produced by Cordyceps ophioglossoides (82)(83)(84). Sixteen years after the initial characterization of ophiocordin, the absolute stereochemical structure of balanol, its isolation from Verticillium balanoides and its low nanomolar inhibitory effects against nearly all protein kinase C (PKC) isoforms were reported (81).…”

Cordyceps – A traditional Chinese medicine and another fungal therapeutic biofactory?

“…Two pure compounds were isolated as active principles from low molecular-weight fractions, and a protein-bound polysaccharide that showed a marked increase in the liver enzyme activities, and a significant inhibition of lipid peroxidation was found. Boros et al (1994) reported that ophiocordin, an anti-fungal antibiotic from Cordyceps ophioglossoides (Kneifel et al, 1977) and balanol from Verticillium balanoides are structurally identical. This may indicate a particularly close taxonomic relationship between the two taxa.…”