Chrysanthemyl pyrophosphate

Chrysanthemic acid (1) consists of ten carbons, suggesting that it is a monoterpene. The cyclopropane ring of the acid moiety is a feature of pyrethrins. Rivera et al. isolated chrysanthemyl pyrophosphate synthase (CPPase or alternatively referred to as chrysanthemyl diphosphate synthase) underlying the formation of chrysanthemyl pyrophosphate (16) containing a cyclopropane ring from two molecules of dimethylallyl pyrophosphate (15) (DMAPP) and the gene thereof [21]. They found that the reaction involves the cF-2-3 cyclopropanation of DMAPPs in a non-head-to-tail manner. 

Similar in importance to hunting for biosynthetic genes is clarifying whether other plant species are able to produce biosynthetic intermediates themselves using high-sensitivity LC-MS. If so, how close are such compounds located to pyrethrins in the pathway It could be that pyrethrin production is too small to be noticed in other plant species. Even if this is not the case, it should be noted that some other plant species produce chrysanthemyl pyrophosphate (16) and r/.v-jasmone (25). 

Certain bacteria are able to form C3Q, C45, and CgQ-isoprenoids of the phytoene type in addition to phytoene by head-to-head condensation of appropriate precursor molecules. In higher plants certain monoterpenes probably are synthesized in a similar manner. Chrysanthemyl alcohol, occurring in Compositae, is an analog of presqualene and prephytoene. The C-skeletons given in Fig. 97 are derived from chrysanthemyl pyrophosphate. Chrysanthemum carboxylic acid is a constituent of the pyrethrins, compounds with marked insecticidal activity (E 5.5.3). 

The first step involves the intermolecular olefin alkylation between two molecules of dimethyl allyl pyrophosphate. A 1,3-proton elimination from the methylene group gives chrysanthemyl pyrophosphate while a 1,2-proton elimination affords the lavandulol skeleton. Of course, these transformations can be equally well represented by formation of either a bridged, non-classical carbonium ion or an intermediate covalently bound to a nucleophile (e.g., X group on an enzyme surface... 

Unexpected results have come to light bearing on monoterpenoid biosynthesis (Chapter 1). Banthorpe s group have shown that in the formation of the thujane and camphor skeletons, activity from labelled mevalonic acid can appear predominantly in the C5 unit supposedly derived from isopentenyl pyrophosphate and only to a minor extent in the dimethylallyl pyrophosphate-derived portion. Banthorpe has also presented evidence for a chrysanthemyl intermediate, analogous to presqualene alcohol, in the biosynthesis of artemesia ketone. 

The controversy over presqualene alcohol has been resolved in favour of Rilling s second structure (5), rather than the diester proposed by Popjak or the acyclic formulation suggested by Lynen. In the biosynthesis from farnesyl pyrophosphate one hydrogen atom is lost to the medium from C-1, and when the presqualene alcohol pyrophosphate is further metabolized to squalene (6) no further hydrogen atoms are lost. Final proof of the structure came from its synthesis by three groups the indicated absolute stereochemistry was based on a correlation with trans-chrysanthemyl alcohol. This structure is now also accepted by Popjak and co-workers. Thus the conversion of farnesyl pyrophosphate into squalene may be rationalized as shown (see also ref 29). 

Little is known of the biosynthetic routes to the irregular monoterpenoids. It has been suggested that chrysanthemyl alcohol is a parent of the class that includes artemisia ketone, lavandulol, and santolinatriene, and stereochemical considerations have indicated that the (1/ , 3i )-isomer (16) of this alcohol would be the required precursor. The alcohol (16) occurs in Artemisia ludoviciana, and this is the first identification of the alcohol from a natural source. The santolinyl compound (17) also occurs in Artemisia tridentata and the 5-stereochemistry at C-3 is as expected if (16) (presumably as its pyrophosphate ester) is a precursor. 

In cell-free extracts of Artemisia annua and Santolina chamaecyparissus, chrysanthemyl alcohol and its pyrophosphate are incorporated into artemisia ketone and alcohol. Artemisia alcohol (95) is converted into artemisia ketone (94) and tranj-chrysanthemic acid in the preparation from S. chamaecyparissus (Banthorpe et al., 1977a). IPP and DMAPP are incorporated into irregular monoterpenes whereas geranyl and neryl-OPP are not. An enzymatic sulf-hydryl group is involved. 

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