Geranyl-geranylpyrophosphate

Fig. 20.3. Schematic representation of the main pathways in the lipid metabolism of parasitic flatworms. Boxed substrates are supplied by the host. Pathways present in mammalian systems but absent in parasitic flatworms are shown by open arrows. Abbreviations DAG, diacylglycerol CDP-DAG, cytidine diphosphodiacylglycerol Farnesyl PP, farnesyl pyrophosphate Geranyl PP, geranylpyrophosphate Geranylgeranyl PP, geranylgeranylpyrophosphate FlMG-CoA, hydroxymethylglutaryl-CoA TAG, triacylglycerol PA, phosphatidic acid PC, phosphatidylcholine PE, phosphatidylethanolamine PI, phosphatidylinositol PS, phosphatidylserine.

These isomeric C5 units condense to form a Cjq compound isopentenyl pyrophosphate attacks an allylic carbonium ion formed from dimethylallyl pyrophosphate to yield geranylpyrophosphate (Figure 26.9). The same kind of reaction takes place again geranyl pyrophosphate is converted into an allylic carbonium ion, which is attacked by isopentenyl pyrophosphate. The resulting C15 compound is called farnesylpyrophosphate. The same enzyme, geranyl transferase, catalyzes each of these condensations. 

Chemoenzymatic synthesis. In parallel to the work of the Li group on C7 [43, 219], Edwards and co-workers recently identified, expressed and characterised the bacterial ferf-prenyltransferase LtxB from the marine cyanobacterium Lyngbya majuscula [28]. It was possible to catalyse the 7-tert-geranylation of indolactam V (1) with geranylpyrophosphate (289) affording the natural product lyngbyatoxin (290) (Scheme 55). 

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