Ophiobolin structure

We have recently isolated two new ophiobolins, G and H, from a novel source, Aspergillus ustus (ATCC No. 38849) (16) (Figures 5 and 6). Structurally, these two compounds are interesting in that the ring fusion between rings A and B is trans, as opposed to cis in the ophiobolins previously described from other fungal sources. In this respect these new metabolites more closely resemble the ophiobolins extracted from insects. Structural features common to both the insect and fungal ophiobolins are the double bonds at C7-C8 and C18-C19. Ophiobolins G and H are unique in the possession of a C16-C17 cis double bond. 

The structure of ophiobolin A (5.137) was established by chemical degradation and by X-ray crystallography of a bromo derivative. The spectroscopic characteristics of ophiobolin A led to the identification of the oxygen functions and the double bonds. The relationship between the aldehyde and the cyclo-pentanone was revealed by the formation of a y-lactone on reduction and partial re-oxidation. A cyclic pyridazine was formed with hydrazine. Tetra-hydro-ophiobolin A formed an unusual cyclic peroxide involving these two groups. Vigorous oxidation of tetrahydro-ophiobolin A afforded a heptanoic acid lactone, which revealed the structure of the side-chain. 

H2]-, [2- C,2R- H,3i ]-, [2- "C,25- H,3K]-, [2- C,3R,4/ - H]-, and [2- C, 3R,4S- H]-mevalonic acids are summarised in formula (69). Glycine is a better precursor than mevalonic acid, but no degradation data was reported. Recent results on fusicoccin (70) suggest that the isopentenyl unit is synthesised at a different rate from the tricyclic system. This result implies that although fusicoccin is structurally similar to the ophiobolins it may represent a new class of diterpenoids. 

Since the appearance of the first review, the elucidation of the structures of the ophiobolins, a group of phytotoxic metabolites from certain plant fungi, has revealed the natural occurrence of compounds possessing a skeleton based on 5 isoprene units, to which the generic term sesterterpenoids has been given. After considerable confusion an agreed nomenclature has been achieved [200] and the first examples of sesterterpenoids are henceforth to be known as the ophiobolins A, B, C and D. 

Nozoe S, Morisaki M, Tsuda K, Itaka Y, Takahashi N, Tkmura S, Ishibashi K, Shirasaka M 1965 The structure of ophiobolin, a C25 terpenoid having a novel skeleton. J Am Chem Soc 87 4968-4970... 

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