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Terpenoids and Steroids Volume 6
A Review of the Literature Published between September 1974 and August 1975
By K. H. Overton
The Royal Society of ChemistryCopyright © 1976 The Chemical Society
All rights reserved.
BY R. B. YEATS
An increase in the published work, coupled with restricted space available for this Report, makes it difficult to be comprehensive and critical. Regretfully some papers remain unreviewed, to be buried deeper in the chemical literature, while others that have eluded the referees escape deserved criticism. The practices of reporting the same results in more than one paper, of reporting work similar to that already published, and of eking out results into an unnecessary number of publications continue, and are to be deplored. In the interests of economy, a number of such papers are omitted from this Report. The change in authorship of this chapter and delay in the receipt of some publications in Canada make it inevitable that some significant papers have not been included; they will be covered in next year's Report. Within these limitations, every effort has been made to cover this year's monoterpenoid literature comprehensively.
A useful volume on the chemistry of terpenoids and steroids has appeared. Nineteen topics in monoterpenoid chemistry are reviewed with a literature coverage to early 1973; the topics are particularly suitable for use in advanced lecture courses and cover biosynthesis, structural elucidation, and synthesis. Monoterpenoid alkaloid chemistry has been reviewed.
1 Physical Measurements: Spectra etc.; Chirality
A useful atlas of chiral molecules has appeared; the major monoterpenoids of known absolute configuration are illustrated, with a literature coverage to the end of 1971. The reader should beware of printing errors: e.g.(+)-β-irone lacks a methyl group at C-2, (-)-(R)-α-cyclogeraniol lacks a double bond between C-2 and C-3, and (+)-δ-carotene has only 39 carbon atoms (p. 131); carvotanacetone is incorrectly indexed and the nomenclature and presentation of thujane monoterpenoids is different from that used in these Reports.
Long-range coupling constants (4J3-exo-5-exo) have been measured in a series of 4-substituted bornanones (1; Y = O) and correlated with σ1; examination of corresponding nitrimines (1; Y = N-NO2) indicates that the polarity of the C=Y bond affects the magnitude of the coupling constant. The conformations of αβ-unsaturated ketones can be determined from the 1H n.m.r. spectra of corresponding free-radical oxazine nitroxides (2) and (3). 1H N.m.r. solvent shifts have been used to identify a tertiary methyl group on a carbon bearing a hydroxy-group, and hexafluorobenzene solvent shifts have been reported for twelve monoterpenoid aldehydes and ketones and shown to conform to the carbonyl reference plane rule. Shifts induced by [Eu(dpm)3] have been used to confirm the structures of 5,5- dimethyl-6-methylenenorbornan-2-exo-ol, the camphanone (4), and the conformation of methyl ([+ or -])-cis-pinonate. An iterative computer programme for simultaneous simulation of lanthanide-induced chemical shifts and spin-relaxation data has been developed and used on borneol. Schneider has computed the most probable lanthanide positions for [Eu)dpm)3]-induced 1H shifts and [Yb(fod)3]-induced 13C shifts for alicyclic compounds including a series of bicyclo[2,2, 1]heptane alcohols and ketones; the C-5/C-6 13C n.m.r. assignments for camphenilone (5; X = O) are shown to be δTMS 23.24 p.p.m. and δTMS524.57 p.p.m. respectively, and not the reverse, as previously reported. A preliminary paper on the TiCL4-induced shifts in the 13C n.m.r. frequencies of carvone, piperitone, camphor, and fenchone has appeared (Vol. 5, p. 3). The trimethylsilyl group has been used to produce 13C n.m.r. shifts for signal assignment in bicyclo[2,2,1]heptanols, e.g. the borneols and α-fenchyl alcohol. Arsenic trichloride is a useful solvent for 13C n.m.r. spectra; however, alcohols and amines exhibit 13C shifts for carbon atoms adjacent to these functional groups; C-2 and C-4 in (-)-menthol occur at 2 p.p.m. upfield from normal and C-3 4 p.p.m. downfield from TMS. Lanthanide shift reagents are compatible with the solvent but [Eu(fod)3] and [Pr(fod)3] show 13C shifts in the opposite direction to those usually observed. The 13C n.m.r. spectra of geraniol, nerol, cis- and trans-chrysanthemum carboxylic acids, and some derivatives have been recorded. Stothers has assigned the 13C n.m.r. frequencies of a series of exo-methylene-norbornanes and has shown that the α-methyl carbon atoms are more shielded in the corresponding ketones than in the exo-methylene derivatives; no difference was observed in the 7,7-dimethyl shifts in camphor and in the corresponding exo- methylene series. A second paper discusses 13C n.m.r. assignments in bicyclic compounds, including some with the pinane skeleton. 13C Spin–lattice relaxation has been reviewed and includes hitherto unpublished data on linalool, 1,2- dihydrolinalool, and 1,2-dehydrolinalool.
Different methods of computer-matching the mass spectra of 122 monoterpenoids give the best results when six to eight of the most intense peaks are matched. The mass spectral fragmentation patterns of various bicyclic ketones of the thujane and carane series, and of their deuteriated [e.g. (6; X = D)] analogues, did not produce any generalizations on the fragmentation patterns or on the deuterium content.
Raman circular intensity differentials (c.i.d.), which are observed in methyl asymmetric deformations and methyl torsions, may be valuable in probing chirality in monoterpenoids; (-)-limonene and (+)-carvone each show a broad, weak depolarized Raman band at 250 cm-1 with a large c.i.d. The origin of these bands is not yet certain.
1-(2-Phenylbutanoyl)imidazole (7) has been used in a modified Horeau analysis to determine the chirality of amines, alcohols [e.g.(-)-menthol], and carboxylic acids, and another exception to the octant rule has been reported, for (3R, 5R]-dimethylcyclohexanone and 3,3,5(R)-trimethylcyclohexanone, both of which have been synthesized from (+)-pulegone. (-)-Menthyl esters continue to find applications in asymmetric induction; asymmetric reduction of substituted (-)-menthyl cinnamates by photochemical hydrostannation and by lithium aluminium hydride or organomagnesium halides have been reported, and also double asymmetric reduction of (-)-men thyI benzoylformate by diphenylsilane and [(+)DIOP]Rh(solvent)Cl (in 60% optical yield compared with only 6% optical yield with 1-benzyl-1,4-dihydronicotinamide in the presence of magnesium perchlo-rate in the simple asymmetric reduction).
Further work on the resolution of monoterpenoids using micro-organisms has been reported (cf. Vol. 5, p. 4): Thus ([+ or -])-bornyl chloroacetate is hydrolysed to (-)-(R)-borneol (78% optical purity), leaving the antipodal trichloroacetate, and racemic trans-chrysanthemyl acetate yields (-) -trans-chrysanthemyl alcohol in low optical purity and unreacted (+) -trans-chrysanthemyl acetate (g.1.c. analysis of this mixture is erroneous!) 31 using Trichoderma sp. Racemic α-cyclogeranyl acetate gives (-)-(S)-α -cyclogeraniol and (+)-(R)-α-cyclogeranyl acetate in low optical purity with Bacillus subtilis var. Niger.
The applications of liquid chromatography to terpenoids have been reviewed. Rapid separation of alcohols (e.g. geraniol–nerolidol, geraniol–citronellol) by metal complex formation has been re-examined.
2 General Synthetic Reactions
Catalytic transfer hydrogenation and the use of monoterpenoids as hydrogen donor compounds have been reviewed.
Pericyclic reactions continue to attract attention. Following the report that silyl ethers of allylic acetates undergo [3,3] Claisen-type rearrangements to γδ-unsaturated acids, the high stereoselectivity of the rearrangement has been demonstrated using geraniol (8) (Scheme 1); the γδ-unsaturated acid (9) has been converted into the Queen Butterfly pheromone (10). Allylic alcohols are converted into βγ-unsaturated NN-dimethylamides on heating with NN-dimethylformamide acetals by a proposed [2,3] sigmatropic rearrangement of a carbene; whereas linalool yields the amides (11) in synthetically useful yields, the method works poorly with γ,γ-disubstituted allylic alcohols such as geraniol (8). The enc-addition of benzyne to (+)-carvomenthene, (+)-limonene, α-pinene, β-pinene, and car-3-ene (the formula is incorrect in the paper) has been investigated.
1,3-Dienes can be synthesized from allylic alcohols under mild conditions by the action of diethylaluminium 2,2,6,6-tetramethylpiperidide on an epoxy-silyl ether (Scheme 2); geraniol (8) yields trans-β-ocimene (13) and nerol yields myrcene (12). Trisubstituted alkenes can be synthesized stereoselectively by treating the nickel complex (14) with an alkyl halide; prenyl bromide yields geranyl benzyl ether. Deuteriated alkenes [e.g. (15)] may now be synthesized in high yield from ketone tosylhydrazones by using tetramethylethylenediamine as solvent.
Selective oxidation of alcohols to aldehydes and ketones in high yields continues to receive attention. Geraniol (8), as the triethyltin alkoxide, is oxidized with bromine and triethyltin methoxide; no double-bond isomerization is reported, in contrast to some isomerization using the Jones reagent. Pyridinium chlorochromate oxidizes citronellol to the aldehyde in buffered solution, but yields pulegone when not buffered. Dimethyl sulphoxide is an excellent solvent for acidic sodium dichromate oxidation. Oxidation of dials with silver carbonate on Celite can be used to synthesize ([+ or -])-rnevalonolactone labelled with deuterium, 13C, or 14C, and isoprene can be converted into 3-methylbut-3-en-1-ol by oxidation of the corresponding [(η5-C5H5)Zr(R)Cl] complex with oxygen. Chromic acid and periodic acid have been used for the oxidative deoximation of camphor. Anodic oxidation of limonene 50 is very similar to that of pinene (Vol. 4, p. 57). The rate constants for reaction of monoterpenoid hydrocarbons with ozone and with NOx have been measured and shown to be more sensitive to hydrocarbon structure for the ozone reaction. It is concluded that the least reactive hydrocarbons are destroyed in the atmosphere by NOx or by some species associated with its photolysis, whereas reactive hydrocarbons would be expected to react with ozone. The endocyclic conjugated diene systems are especially reactive with ozone (as expected!).
Regeneratable polymeric organotin dihydride beads have been used to reduce halides selectively (e.g. 3-bromocamphor to camphor). β-Unsubstituted cyclohexenones undergo exclusive and almost quantitative 1,4-reduction by potassium tri-s-butylborohydride to the corresponding saturated ketone [e.g. (16)]; reductive alkylation of carvone proceeds similarly to (17; R = Me, X = H). In contrast, sodium cyanoborohydride in acidic methanol or hexamethylphosphoramide gives mixtures of allylic and saturated alcohols. Reductive deoxygenation of αβ-unsaturated p-tosylhydrazones with sodium cyanoborohydride in acidic DMF–sulpholane yields E geometrical isomers stereoselectively, probably via a [1,5] sigmatropic rearrangement of an intermediate diazene; pulegone yields menth-3-ene.
The reaction of Gilman reagents with αβ-epoxy-oximes yields β-hydroxy-ketones [e.g. (17; X = OH)]. Vinyl copper compounds are converted stereo-specifically into β,β-disubstituted α-ethylenic acids by carbonation; nerol (18) was synthesized (Scheme 3). Further papers on β-ketosulphoxide synthesis [e.g. of (19)] and on the application of α-sulphinylcarbonyl and related compounds to alkylative elimination have appeared. Other synthetically useful reactions are stereospecific dehalogenation using [HFe(CO)4]-, formation of mesylates using 'easy mesyl' (MeSO2NMeEt2+ FSO3-), graphite bisulphate esterification, conversion of alcohols into amides by chlorodiphenylmethylium hexachloroantimonate, dihydrofuran formation [e.g. (20)] from the photochemical irradiation of αβ-unsaturated ketones in the presence of methanol and TiCl4, and the conversion of nitrimines [e.g. (21)] into amides [e.g. (22)] using KCN.
3 Biogenesis, Occurrence, and Biological Activity
A monograph on the chemotaxonomy of flowering plants extensively lists plant products and their occurrence by broad chemical type; however, lists are not complete, as of 1969, and detailed references are not usually given. A classic lexicon of fragrant materials has been completely revised, a review of essential oil analysis covering the period September 1972 to August 1974 has been published, and volatile leaf oil analysis in chemosystematic studies has been reviewed.
Synthesis of labelled mevalonolactones continues to receive attention, and new syntheses of ([+ or -])-, (R)-, and (S)-mevalonolactones have been reported. The isolation of the energy-rich carboxylic ester (23) of prenyl mercaptan prompts the search for f urther naturally occurring sulphur compounds and their significance in terpenoid biogenesis. A thiol is essential to both the enzymatic and non-enzymatic isomerization of geraniol (8); no aldehydes and no linalool were observed. Banthorpe has shown that the biosynthesis of (+)-thuj-3-one (24; 2S) from [14C]-acetate again exhibits asymmetric labelling (cf. Vol. 3, p. 7), the 14C label being pre-dominantly in the IPP-derived portion. Similar results are obtained with geraniol (8) and (+)-pulegone and suggest the existence of metabolic pools of acetyl-CoA.
The suggestion of an alternative non-mevalonoid route in monoterpenoid biosynthesis has received some support in the efficient incorporation of L-[U-14C]valine into the DMAPP moiety of linalool; 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. (1R,3R) -Chrysanthemic acid (25) is biosynthesized in Chrysanthemum cinerariaefolium from (1 R, 3 R)-chrysanthemyl alcohol (26) but not from precursors with the lavandulyl (27) or artemisyl (28) skeletons (Scheme 4); (1 R, 3 R)-chrysanthemyl alcohol (26) has been isolated from the leaves of Artemisia ludoviciana. In connection with the suggestion that cyclobutane derivatives may be involved in the biogenesis of artemisyl and santolinyl skeletons, the cyclobutanol (29) has been synthesized from (-)-α-pinene. For further work on monoterpenoid biosynthesis, see Chapter 6, p. 177.
A Pseudomonas strain hydroxylates p-menthane to cis-p-menthan-1-ol, and microbiological reduction of carvotanacetone with Pseudomonas ovalis gives similar results to those obtained with carvone (Vol. 5, p. 24, incorrectly reports inversion at C-4). (-)-Carvotanacetone (30) gives (+)-carvomenthone (31), (-)-carvomenthol (32; X = H), and the corresponding (+)-neocarvomenthol, whereas (+)-carvotanacetone is reduced to (-)-isocarvomenthone (33; X = O), (-) -carvomenthone, and the isocarvomenthols (33; X = H, OH). A further paper describes the C-1 epimerization of isodihydrocarvone (16; 1 R) to dihydrocarvone (16; 1S) by Pseudomonas fragi.
The analysis of essential oils which contain monoterpenoids has contributed many papers to the literature this year; a disturbing number of analyses are trivial and furnish little that is new. The validity of the natural occurrence of minor components can be questioned in the light of isolation technique; linalyl acetate yields eleven monoterpenoids on steam distillation. Analyses of interest are: the major component (58%) of the steam-volatile leaf oil of Zieria aspalathoides is (-)-car-3-en-2- one; (+)-2,6-dimethyloct- 7-en-4-one is the major component (97%) in Phebalium glandulosum subsp. glandulosum; major components in Achillea millefolium essential oil (isolated by steam distillation!) are sabinene and artemisia ketone, which is incorrectly named by the authors as isoartemisia ketone (possibly from Devon and Scott's Handbook); essential oil from Salvia dorisiana contains perillyl acetate and the rare methyl perillate (34; R = CO2Me); tricyclene is present in Agathis australis as a major component, and cis-carveyl acetate is a major component in Japanese spearmint (Mentha spicata crispa). Some rare oxygenated menthanes have been isolated from Mentha gentilis, and from Piper nigrum.
Excerpted from Terpenoids and Steroids Volume 6 by K. H. Overton. Copyright © 1976 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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Table of Contents
ContentsPart I Terpenoids,
Chapter 1 Monoterpenoids By R. B. Yeats, 3,
Chapter 2 Sesquiterpenoids By N. Darby and T. Money, 52,
Chapter 3 Diterpenoids By J. R. Hanson, 96,
Chapter 4 Triterpenoids By J. D. Connolly, 118,
Chapter 5 Carotenoids and Polyterpenoids By G. Britton, 144,
Chapter 6 Biosynthesis of Terpenoids and Steroids By D. V. Banthorpe and B. V. Charlwood, 169,
Part II Steroids,
Chapter 1 Steroid Properties and Reactions By D. N. Kirk, 221,
Chapter 2 Steroid Synthesis By P. J. Sykes and J. S. Whitehurst, 276,
Author Index, 345,