Dimethylallyl pyrophosphate incorporation

Introduction of the isoprenyl groups at C-5 and C-7 in echinulin (115) has been shown, by the results of [5(i )-3H]- and [5(S)-3H]-mevalonate incorporations, to proceed with normal inversion of configuration at C-5 (mevalonate numbering) in the intermediate dimethylallyl pyrophosphate. The pattern of incorporation of [l,2-13C2]acetate indicates that the stereochemistry at the double-bonds is the same as that of dimethylallyl pyrophosphate.42... 

The main advances in monoterpenoid biogenesis have been achieved by Ban-thorpe s group, who have extended their work (published earlier in note form) on the thujane derivatives obtained from Thuja, Tanacetum, and Juniperus species. More than 90 % of the label from [2- C]mevalonic acid is incorporated in that part of the skeleton derived from isopentenyl pyrophosphate, the part supposedly derived from 3,3-dimethylallyl pyrophosphate being essentially unlabelled. These results are not consistent with the accepted view that both isopentenyl and... 

Except for studies involved with characterization of the enzyme, there is little relevant material in the literature concerning the mechanism of the reaction. The incorporation of from water into isopentenyl pyrophosphate and dimethylallyl pyrophosphate has been determined. The exchange was substantially faster with isopentenyl pyrophosphate and the label was located primarily on C-4. The results were interpreted in terms of a mechanism in which a carbonium ion, formed by protonation, partitions between the two substrates and a covalent adduct with the enzyme (Fig. 9). A covalent substrate adduct was reported, but this undoubtedly resulted as an artifact of the experimental procedures used [6]. 

The direct incorporation of dimethylallyl pyrophosphate into carotenoids has not been reported. The incorporation of geranyl pyrophosphate into carotenoids has not been demonstrated either, but Varma and Chichester (1962) showed the incorporation of free geraniol into jS-carotene by carrot root slices. This result, plus those of later studies, indicate that higher plants... 

In a particularly provocative study, Gorst-Allman et al. fed [ 1,2--labeled acetate and [2,3- C]-labeled mevalonic acid lactone to cultures of Penicillium roqueforti and Penicillium crustosum [45] The NMR spectrum of the roquefortine showed that both C(26) and C(27) were coupled to C(23) (Fig. 9). This interesting result mandates that, during the incorporation of dimethylallyl pyrophosphate, the methyl groups become quasi-equivalent. 

The findings that mevalonate entered into the ergoline structure in some form of an isoprene unit and that labelled 4-(y,Y-dimethylallyl)pyrophosphate (DMAPP) was incorporated intact into alkaloids (Plieninger et al., 1967) established 4-(Y,y-dimethylallyl)tryptophan (DMAT, 17) as the structural... 

Cell-free extracts and acetone powder preparations from Agave amerkana have been shown to phosphorylate mevalonic acid to give phosphomevalonic acid and thence pyrophosphomevalonic acid at an optimum pH of 7.0. Glutathione and mercaptoethanol enhance the activity of these preparations. Tracer studies with tissue cultures derived from Tanacetum vulgare have revealed the formation of phosphomevalonic acid, pyrophosphomevalonic acid, isopentenyl pyrophosphate, dimethylallyl pyrophosphate, and the incorporation of mevalonic acid into monoterpenes. However, the mono-terpene components of the tissue culture differed from those of the whole plant, sabinene being formed rather than isothujone. 

R,5 )-[2- C] Mevalonate was incorporated 50 times better than (35)-[2- " C]mevalonate, indicating that (3R)-mevalonate is the precursor of the ergot alkaloids (Floss et al., 1968). This is the same isomer that is incorporated into squalene via dimethylallyl pyrophosphate in rat liver. In a related experiment, when a mixture of (R5)-[2- " C]mevalonate and (3R,55)-[5- H]mevalonate was fed, the ratio doubled owing to incorpora-... 

Mevalonic acid (MVA) is transformed into isopentenyl pyrophosphate (IPP) by decarboxylation, and is further transformed into dimethylallyl pyrophosphorate (DMAPP). IPP and DMAPP are the fundamental building blocks that are incorporated into terpenoids. Terpenoids are therefore regarded as compounds derived from the combination of multiple C5 units. These biosynthetic pathways are demonstrated by specific incorporation studies with T( H)- and C-labeled compounds [2-5],... 

In 1973, Allen demonstrated that the monoprenylated cyclic dipeptide cyclo-L-alanyl-2-(l,l,-dimethylallyl)-L-tryptophan was incorporated into echinulin in cultures of Aspergillus amstelodami [56]. In this study, the reverse prenyiated cyclic dipeptide was doubly labeled with and by treating a partially purified prenyl transferase obtained from Aspergillus amstelodami with cyclo-L-Ala-L-[3- C]-Trp and [l- H]-3-methyl-2-butenyl 1-pyrophosphate (Scheme 33)... 

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