Part I

TERPENOIDS

The interesting formal parallel that exists between the rearrangements of the chrysanthemyl cation and the conversion of presqualene alcohol into squalene (and now of prephytoene alcohol into phytoene) has been further explored. Solvolyses of the cyclopropyl (65) and cyclobutyl (63) esters both afford head-to-head coupled C10 chains analogous to squalene. A versatile new method provides access to 9-substituted p-menthanes. This starts with natural limonene and proceeds via the anion (135) which retains chirality and leads to chiral products (see below). Skeletal rearrangements in the bicycloheptane series, an historic field in the study of organic reaction mechanisms, has received a fresh impetus from the extended work of Kirmse and his colleagues, which is of preparative and mechanistic significance.

Excellence and diversity in the synthetic field again characterize the year's work on sesquiterpenoids, with some notable examples of sophisticated methodology on the industrial scale. The production of C17 and C18 juvenile hormones and the conversion of the C17 into the C18 hormone are cases in point. The metallation of limonene referred to above has been turned to good account in stereospecific routes to bisabolane sesquiterpenoids. The unique antibiotic fumagillin has been synthesized 36 by an imaginative route. Two notable syntheses of zizaene have been reported. Wiesner's approach utilized a synthetic route to bicyclo[3,2,1]octanes developed in the course of an approach to diterpene alkaloids. The labile trans,trans-1,5-cyclodecadiene system of hedycaryol has been successfully generated by Marshall fragmentation of the appropriate cyclo-octyl tosylate. Ourisson has described a simple two-stage procedure whereby the α-methylene-γ-butyrolactone function so widespread among natural sesquiterpenoids can be obtained from the more readily available α-methyl-γ-lactones. The method succeeds only with cis-fused lactones. The in vitro interconversion of acyclic, mono-, bi-, and tri-cyclic sesquiterpenes and their potential relevance to biosynthesis continue to attract widespread experimental attention and the complex acid-catalysed rearrangements of thujopsene have been subjected to penetrating study. An attempt to systematize the nomenclature of germacranolides should be noted by workers in the field.

Much effort in the diterpenoid field is concentrated on substances having biological activity. Thus the coleons, inumakilactones, and podofactones control the expansion and division of cells. Combined g.l.c. and mass spectrometry has played an important part in the detection and characterization of new gibberellins and there have been important advances in gibberellin synthesis. The antheridium-inducing factor of ferns has a gibberellin-like structure. Cyathin A3, isolated from the 'bird's nest' fungus, represents a novel mode of cyclization of geranylgeraniol. Notable synthetic successes in the diterpene alkaloid field have come from Wiesner's laboratory in the total synthesis of the delphinine degradation product (158) and the intermediate (159) for a synthesis of songorine.

Cheilanthatriol 1 represents a new type of sesterterpenoid whose carbon skeleton resembles that of triterpenoids.

The structure of Baccharis oxide has been revised; biosynthetically this is close to the previous structure (Vol. 2, p. 168) and therefore of comparable interest. The total laboratory synthesis of lupeol is a notable further achievement in the synthesis of unsymmetrical triterpenoids.

Cornforth and his colleagues have investigated the stereochemistry of isomerization of isopentenyl to dimethylallyl pyrophosphate in isoprenoid biosynthesis. They find that the prototropic change involved is stereochemically different from the superficially analogous association of C5 units. Bisabolene appears to be excluded as an intermediate in the biosynthesis of helicobasidin and trichothecin by recent labelling studies (see also Vol. 1, p. 232, ref. 81) and a 1,4-hydride shift in the initially formed intermediate is indicated. The loss of the C-14 methyl group in cholesterol biosynthesis differs from loss of the C-4 methyl groups. The 32-carbon atom is released at the aldehyde oxidation level as formic acid.

In the carotenoid and polyterpenoid field a number of important stereochemical studies have appeared. These include assignments of the complete stereochemistry of phytoene and lutein and the absolute configurations of absicic acid and the natural irones.

1

Monoterpenoids

BY A. F. THOMAS

The volume of work published on monoterpenoids is increasing, not only in the absolute sense, but relative to that on other natural products (including other terpenoids). There are at least three possible causes : many monoterpenoids are plentiful, further exploitation is desired, and recent refinements of analytical techniques have made possible the examination of reaction detail that was previously inaccessible. Monoterpenoids lend themselves especially well to such studies because of their suitability for gas chromatography, and also provide examples of a wide variety of structural types. Chemotaxonomy is also increasingly moving toward the use of monoterpenes because of the simplicity of analysis.

Duplication of previously published work (see Vol. 2, p. 5) is reaching new levels. It is incomprehensible that reputable journals (in some cases) with a good refereeing policy still do not detect earlier work-even when it has appeared in this and other reviews-and this year an attempt has been made to quote the earlier reference (this is rarely done by the later authors) in order to highlight the problem.

1 Analytical Methods and General Chemistry

The first of two books with monoterpenoid sections is of the 'dictionary' type. It would be useful were it not for the incredible number of errors. Space will not permit a full criticism, but they include incorrect formulae (carquejyl acetate, artemisia and isoartemisia ketones, linalool, linalool oxide, lippione), double bonds of incorrect geometry (yomogi alcohol, cosmene), the inclusion of many discredited or doubtful compounds (santolinenones, osmane, hymentherene, etc.), and a very unusual biogenetic scheme. The other book purports to give a brief introduction to the chemistry, but terpenoids related to chrysanthemic acid, iridoids, ortho-menthanes, and heterocyclic terpenoids are omitted, and there are only 236 references, eight of which are post-1969 and twenty post-1968. Omission...