246 JOURNAL OF TIlE SOCIETY OF COSMETIC CHEMISTS (62) Yamazaki, M., Matsuo, M. and Arai, K. Biosynthesis of dendrobine. Chem. Pharm. Bull. Tokyo 14 1058 (1966). (63) Biollaz, M. and Arigoni, D. Biosynthesis of coriamyrtin and turin. Chem. Comm. 633 {1969). (64) Corbella, A., Gariboldi, P., Jommi, G. and Scolastico, C. Biosynthesis of turin. Chem. Comm. 634 (1969). (65) Noddie, R. C. and Robinson, D. R. Biosynthesis of abscisic acid: incorporation of radio- activity from [2-14C] mevalonic acid by intact fruit. Biochem. J. 112 547 (1969) (66) Taylor, H. F. and Smith, T. A. Production of plant growth inhibitors from xanthophylls: a possible source of dormin. Nature 215 1513 (1967) Taylor, H. F. Carotenoids aspossible precursors of abscisic acid in plants. Soc. Chem. Ind. •1Ionograph B1 22 (1968). (67) Milborrow, B. V. Current research on abscisic acid. Blochem. J. 114 1P (1969) Robinson, D. R. and Ryback, G. Incorporation of tritium from [(4R)-4- 3HI mevalonate into absci sic acid. Blochem. J. lib 895 (1969). DISCUSSION DR. P. J. DUN?HY: In view of the probable necessity for a 2,3 (cis) double bond (nerol) or the isomeric linalool, as the precursor in the biosynthesis of cyclic monoter- penes is it possible that the generation of such double bonds proceeds by direct cis synthesis, as in Hevea (polycis) rubber rather than through the all-trans isomer geraniol? THE LECTURER: On paper this certainly seems quite reasonable. The present evidence, however, suggests that all the monoterpenes and sesquiterpenes (and in fact direrpenes, triterpenes and carotenoids) are derived from an all-trans precursor. There is nothing inherently wrong with a cis double bond, but studies with stereo- specifically labelled mevalonic acids so far completely eliminate that possibility. With [4R-3H] mevalonic acid the tritium atom is retained when a trans double bond is generated. In the few cases where this has been studied the 4 R tritium atom is in- corporated. There is no example of 4 S incorporation. Fig. 12, for instance, shows abscisic acid. The 4 R tritium atom of mevalonic acid is incorporated, not 4 S, although there is a cis double bond. Hence there must have been an isomerization of the double bond with retention of the vinyl proton in the biosynthesis. DR. DUN?HY: Equally there are systems where you get direct cis synthesis and the epimeric proton is retained. Hevea rubber is a good example of this with a poly cis system. THE LECTURF. R: This is the only one though. DR. DUNPH¾: In fact there is a mixed system as well. Many of the poly isoprenoid alcohols, which are poly cis/trans alcohols, appear to be generated in this way. The trans double bond is synthesised, as you would expect, with the retention of the 4 R proton of mevalonic acid, while with the cis double bond it is the other proton that is retained. THE LECTURER: This is right. Polyprenols are long chain terpenoid alcohols, composed of 6-24 isoprene units. Most of them appear to contain only two or three trans double bonds, the remainder being cis. In their biosynthesis three or four (i.e. including the terminal double bond) isoprene units retain the 4 R proton of mevalonic acid and the remainder retain the 4 S proton. This evidence suggests that the plant

THE BIOGENESIS OF TERPENOID ESSENTIAL OILS 247 produces all trans farnesyl pyrophosphate, or all trans geranyl geranyl pyrophosphate, and then synthesises these higher isoprenoid compounds, by adding on cis isoprene units. This conclusion is somewhat speculative because the position of the tritium atoms along the chain has not been identified however, it is certain that enzymes able to generate cis double bonds are present. The biosynthesis of the indole alkaloids proceeds via the monoterpenoid loganin (Fig. 8). In this case the 4 R proton of mevalonic acid is retained by all trans geraniol, so that an isomerization to nerol must have occurred before cyclization to the cyclo- --pentanyl monoterpenoid. A MEMmER OF T•E AUDIE•CE: I was surprised when you were discussing dimethyl- allyl pyrophosphate and mentioned the stereo chemistry of the methylene carbon atom. This thrilled me quite considerably as I thought at least this part was elementary --and that one would not have expected any asymmetry at this carbon atom. TaE LECTURER: Most of the work I have described was conducted by Popj&k and Cornforth (4) who, in particular, were studying squalene biosynthesis. However, I am certain that their results can be applied to all terpenoids, and I think it came as a surprise to a lot of people that it was so stereo specific. At any stage where the enzyme has to select one of two atoms (where the organic chemist would say that there is nothing to choose between them) the enzyme in every respect appears to stereo specifically select only one of the two hydrogen atoms. Although they have not yet proved, as far as I am aware, that an "optically active methyl group" is generated (Fig. 1), I think there is every chance it will be found to be so. Certainly a number of other enzyme systems do involve "optically active methyl groups". An enzyme is made up of optically active a-amino acids, so that the enzyme is optically active in its own right. Hence it will normally generate an optically active product even though the starting material was optically inactive. MR. D. E. BUTTERFIELD: Would you comment on possible practical applications of the knowledge of biogenesis for the future? TaE LECTUREm It is, of course, always very difficult to speculate in this way and one is almost bound to be caught out, but on the other hand I think one could make one or two comments. As I see essential oil chemistry developing, one is more and more going to require specific compounds. However, the plant certainly has the edge on the chemist in its ability to generate those trace components which give a particular fragrance or aroma. From the commercial point of view essential oils are an important source of complex molecules. In many cases the organic chemist can synthesise with great difficulty and in very small yield, a number of these compounds, but if we want to use them as a raw material it is necessary to use the natural source. Hence the problem is that if a particular compound is known to be produced by a plant in the remote Amazon jungle it may not be a useful commercial source. One then wants to consider where there might be a useful source of this particular compound. I think that this is where biosynthesis may have a part to play. The methods by which plants generate these complex molecules can often be related to our knowledge of plant taxonomy one is complementary to the other. This suggests the botanical families or species which might be worth investigating if one is looking for a particular compound.