Farnesyl pyrophosphate, folding

The labelling pattern of paniculide (2) derived from [1, 2- T ]acetate in callus cultures of Andrographis paniculata demonstrates that the folding of farnesyl pyrophosphate in the biosynthesis of (2) must be as shown in Scheme 2 [9]. This is an example where the increased sensitivity associated with doubly labelled acetate was essential. 

Aspergillus stellatus. This supports its biosynthesis via cyclisation of geranyl-farnesyl pyrophosphate followed by rearrangement as shown in Scheme 3 [10]. Surprisingly, the folding pattern must be different from that involved in the biosynthesis of stellatic acid (4), a previously isolated sesterterpene metabolite of A. stellatus [11]. 

Further studies on the biosynthesis of the trichothecane sesquiterpenoids (Vol. 8, p. 74) have shown that the coupling pattern in trichothecin (156) derived from [l,2- C2]acetate is consistent with the previously established route to this compound (cf. Scheme 14) and excludes an alternative folding of the farnesyl pyrophosphate (153) precursor/ The prodigious efforts of the late Professor S. 

In order to distinguish conclusively between the two possibilities of folding the chain, [1- H2,2- " C]- and [2- H,2- " C]farnesyl pyrophosphates were used as precursors of trichothecin (26) in Trichothecium roseum (Achilladelis et ai, 1970, 1972). The incorporation of [l- H2,2- C]farnesyl pyrophosphate was accompanied by the elimination of one tritium label. No tritium was lost from [2- H,2- " C]farnesyl pyrophosphate. In a similar experiment, [l- H2,2- " C]farnesyl pyrophosphate was fed to Trichoderma sporulosum to afford trichodermol (6). Again, only one of the two tritium labels was retained. 

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