Chrysanthemyl alcohol

The suggestion of an alternative non-mevalonoid route in monoterpenoid biosynthesis77 has received some support in the efficient incorporation of L-[l/- 4C]valine into the DMAPP moiety of linalool 78 a pathway via deamination to dimethylacrylic acid is proposed. L-Leucine and l-valine are also incorporated, at least in part, into the DMAPP moiety of geraniol (8) and citronellol.79 (lf ,3/ )-Chrysanthemic acid (25) is biosynthesized80 in Chrysanthemum cinerariaefolium from ( R,3R) chrysanthemyl alcohol (26) but not from precursors with the lavandulyl (27) or artemisyl (28) skeletons (Scheme 4) (li ,3R)-chrysanthemyl alcohol (26) has been... 

C,3H]Chrysanthemyl alcohol (17) was incorporated in relatively large amounts (0.7—2.0%) into chrysanthemic acid and pyrethrins by flowers of Chrysanthemum cinerariaefolium,61 and the 14C 3H ratio of the substrate was preserved in the product. In contrast, [14C]lavandulol, [3H]artemisyl alcohol (18), and the [14C]-diol (19) were not incorporated under similar conditions. Although probably correct, the... 

In the laboratory, however, the route from prenyl ethers or thioethers to artemisia compounds and thence to the santolina skeleton is possible, and an interesting conversion to the lavandulyl skeleton of prenyl compounds has been described. A mixture of 3-methylbut-2-enyl acetate (44) (or chloride) and 3-methylbut-2-enylthiol acetate (45) is treated with aluminium chloride or zinc chloride, when, in addition to the thioether (46), 19% of the lavandulylthiol acetate (47) and 6% of the corresponding isolavandulyl compound (48) are formed. An ingenious two-step synthesis of trans-chrysanthemyl alcohol (49) has also been achieved from prenyl alcohol (50) and 3-methylbut-l-yn-3-yl... 

The relative stereochemistry of the substituents attached to the cyclopropane ring of presqualene alcohol received further confirmation by a synthesis of the triacetate (13), obtainable from (1) by ozonolysis, reduction, and acetylation. Treatment of 3-methyl-truns-hex-2-ene-l,6-diacetate (14) with ethyl diazoacetate in the presence of copper powder gave two isomers (15) and (16) whose stereochemistry was assigned by n.m.r. The triacetate derived from synthetic (15) by reduction and acetylation was identical in all respects with the triacetate (13) from natural presqualene alcohol. Presqualene alcohol has a c.d. curve similar to, but of opposite sign to, that of (li ,2i )-trans-chrysanthemyl alcohol (17). The mechanism for the stereospecific biosynthesis of squalene from farnesol via presqualene alcohol has received detailed comment. ... 

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. 

It is of interest that in some nonenzymatic studies, a small percentage of head-to-head condensation products are observed. Chrysanthemyl alcohol (92) is an analog of presqua-lene alcohol and prephytoene (see Chapters 23 and 26), but the fissions postulated to lead to the irregular monoterpenes have no counterparts for the higher classes (Charlwood and Chari wood, 1991a). 

Label from (3/ , 4/ )[4- H] mevalonic acid but not from (3/ ,45 )[4- H]mevalonic acid was incorporated into chrysanthemic acid (93). Chrysanthemyl alcohol is an intermediate in the biosynthesis of chrysanthemic acid (Pattenden et al., 1975). 

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. 

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). 

Bates, R. B., and D. Feld Terpenoids. XIII. Conversion of Chrysanthemyl Alcohol to a Triene with the Artemesia Ketone Skeleton. Tetrahedron Letters 1967, 4875. 

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