Aliphatic and Related Natural Product Chemistry Volume 3

A Review of the Literature Published During 1980 and 1981

By F. D. Gunstone

The Royal Society of Chemistry

Copyright © 1983 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-662-8

Contents

Chapter 1 Natural Acetylenic and Olefinic Compounds By C.M. Scrimgeour, 1,
Chapter 2 Acyclic Terpenoids By D.H. Grayson, 26,
Chapter 3 Insect Pheromones and Related Natural Products By R. Baker and J.W.S. Bradshaw, 66,
Chapter 4 Prostaglandins and Leukotrienes By R.F. Newton, S.M. Roberts, R.H. Green, and P.F. Lambeth, 107,
Chapter 5 Fatty Acids and Glycerides By F.D. Gunstone, 209,
Chapter 6 Lipids By W.W. Christie, 250,
Chapter 7 Olefinic Microbial Metabolites, including Macrocyclic Compounds By R.C.F. Jones, 288,

CHAPTER 1

Natural Acetylenic and Olefinic Compounds

BY C. M. SCRIMGEOUR

1 Introduction

This report covers the same topics as the corresponding chapter in the previous volume, but in addition includes acetylenic and olefinic compounds of marine origin. Acetylenic compounds form the bulk of the material, the olefinic compounds being those which are not covered by other chapters. The literature covered is that for 1980-1.

2 Natural Acetylenic Compounds

2.1 Introduction.- The results reported during this two-year spell continue the pattern previously noted. A number of new compounds are described and known compounds are recorded from new sources. Two tools are increasingly used – high performance liquid chromatography (h.p.l.c.) and high field (≥ 270 MHz) nuclear magnetic resonance (n.m.r.) spectroscopy. Very little new synthetic methodology has been reported.

2.2 New Polyacetylenic Compounds from Terrestrial Plants. – The majority of new compounds have been isolated from members of the large Compositae family, and many are reported as a result of Bohlmann’s continuing study of this family. Most are closely related to known structural types and their structures therefore follow easily from spectral data. The growing use of high resolution n.m.r. for this purpose is apparent. Unless otherwise indicated the species mentioned belong to the Compositae.

Two C17 hydrocarbons (1) and (2) were isolated from Leucanthemum adustum. Three sources have revealed oxygenated C17 compounds of closely related structure. The epoxides (3) and (4) were isolated from Cacosmia Pugosa and Cirsium japonicum respectively, while the mixture of diacetates (5) and (6) was found in two Ptilostemon species.

A number of new C17 compounds related to falcarinol have also been reported. The acetate (7) occurs in Viguiera incana along with dehydrofalcarinol. Panax ginseng (Araliaceae) contains the epoxide (8). This compound could also be obtained from falcarinol by epoxidation and the structure was further confirmed by synthesis. P. ginseng also contains the dial (9), and mass spectral data are reported for both (9) and the saturated dial obtained by hydrogenation. The absolute configuration of falcarindiol (10) is 3R, 8S, which was shown by examination of the dial and mono -ol mixture obtained by hydrogenation. A C15 acetate (11) with a structure related to falcarinol has been isolated from Helianthus angustifolius.

Two C16 amides (12) and (13) occur in Achillea tomentosa along with a number of related olefinic amides.

The C14 angelate ester (14) occurs in Senecio clevelandii. Interestingly, the isolation of this compound is reported along with that of the first known acetylenic monoterpene (15) and the related olefin (16). It is suggested that the co-occurrence of (14), (15) and (16) may support the assumption that the acetylenic bond is formed by dehydrogenation of a cis double bond. Lycopersicon esculentum (Solanaceae) produces (17) along with falcarindiol and falcarinol after inoculation with Cladosporium fulvum. This is believed to be the first report of polyacetylenic phytoalexins from the Solanaceae. Compound (17) has subsequently been found in tomato plants infected with Verticillium albo-atrum.

A number of new C13 compounds are reported. The isovalerate (18) occurs in some Leucanthemum species along with many other acetylenic compounds. Carlina diae contains (19) and the carlina oxide derivative (20) in addition to other known compounds including carlina oxide. This is taken as confirmation of the taxonomic reclassification of this species to the genus Carlina. Three new thiophen chlorohydrins (21) – (23) are reported from Pterocaulon virgatum, along with two known compounds of this type. The dithienylacetylene (24) has been isolated from Porophyllum ruderale, and another dithienyl compound (25) occurs in Calea pilosa.

Two new phenols C12 (26) and (27) occur in Leuoanthemum segetum. A mixture of seven new aromatic amides (28) – (34) ranging in chain length from C9 – C12 was isolated from Spilanthes alba.

A number of C10 compounds related to matricaria ester are reported. Baccharis quitensis contains (35) and (36) in addition to related known compounds. Four new matricaria ester isomers (37) – (40) were isolated from the rabbit brush, Chrysothamnus nauseosus The rabbit brush is a desert plant, known to be resistant to attack by the Colorado beetle. The extracted mixture of (37) – (40) was shown to have an anti-feedant effect on the beetle larvae and this type of naturally occurring compound is suggested as an environmentally acceptable pest control agent. Dimerostemma asperatum contains two unusual lachnophyllum esters (41) and (42). The fungus Fayodia bisphaerigera produces the methyl ester (43) and the amide linked amino acid derivatives (44) and (45) which are the first reported compounds of this type. These structures were confirmed by synthesis.

Fuller details have now been published of the monoacetylenic γ-lactones described in the previous review. The original report described these as coming from Licaria mahuba (Lauraceae) , but this plant has now been reclassified as ciinostemon mahuba.

2.3 KnownPolyacetylenic Comeounds from Terrestrial Plants. – A large number of new sources of known polyacetylenic compounds have been reported, mainly by Bohlmann and co-workers, often as an offshoot of their studies on the Compositae terpenes. These new sources are recorded in Table 1, along with the major compound types isolated from them. Known compounds which were isolated along with the compounds described in the previous section are not included in the table.

A useful method of visualising polyacetylenes on TLC plates has been described. Vanillin and p-dimethylaminobenzaldehyde were found to be the best reagents for locating a large variety of polyacetylenes. The combination of RF and the colour produced by the two spray reagents allowed twenty-five acetylenic compounds to be distinguished.

2.4 Acetylenic Compounds of Marine Origin. – A number of acetylenic compounds have been isolated from a variety of marine organisms, including molluscs,sponges and seaweeds. The nudibranch mollusc Diaulula sandiegensis contains nine chlorinated C16 acetylenes, (46) – (54). These unstable compounds were easily extracted from the intact mollusc and were separated by repeated reverse-phase liquid chromatography. The structures are based on spectroscopic data, particularly 360 MHz 1H n.m.r. spectra, and some chemical transformations. Neither these compounds nor any likely precursors were present in the sponges which form the mollusc’s diet, and it is suggested that the chloroacetylenes are chemical defence substances.

The Mediterranean nudibranch Peltodoris atromaculata and its prey, the sponge Petrosia ficiformis, contain a number of common metabolites and these have now been shown to include a number of very long chain acetylenic compounds (55) and (56). These C71 to C89 compounds are believed to be the highest molecular weight natural acetylenes known and they were isolated by reverse phase h.p.l.c. The structures followed from 1H and 13C n.m.r. spectra and chemical transformations and the structure of the terminal grouping was confirmed by synthesis. A complex mixture of polyacetylenic acids was also isolated, but not characterised. P. ficiformis is normally red-brown due to the presence of a symbiotic alga. Sponges of this species living in dark caves lack the alga and are white. In a further study these white sponges have revealed the acetylenes (57) – (60) similar but not identical to those found in the coloured sponges.

The red marine alga Liagora farinosa contains three acetylenic lipids (61) – (63). The structures are based on 1H and 13C n.m.r. and other spectra. The compound (61) shows unexpected acute toxicity to the reef-dwelling fish Eupomacentrus leucostictus. (63) is a chronic toxin while (62) is non-toxic.

A number of non-terpenoid C15 acetylenic metabolites are known from the red alga genus Laurencia. These usually show structures containinq cyclic ethers and bearing halogen substituents but are believed to be produced from acyclic polyenyndiols. Laureepoxide (65) is a new compound of this type isolated from L. nipponica. The structure and stereochemistry of laurencienyne (65), isolated from L. obtusa, have been determined by X-ray and spectroscopic methods. The structure of laurenyne (66) from the same source has similarly been determined. The insecticidal compounds laurepinnacin (67) and isolaurepinnacin (68) were isolated from L. pinnata. These structures are unusual in having 12R, 13R stereochemistry respectively unlike almost all the related compounds which show 12R, 13S or 12S, 13R stereochemistry. It is suggested that they are produced from the tetraenyne (69) rather than 12E-laurediol (70). Two non-oxygenated polyenynes (71) and (72) have been isolated from L. okamurai and it is suggested that these are also precursors of the cyclic metabolites. The structures of (71) and (72) were confirmed by synthesis. The green alga Caulerpa prolifera contains the monoacetylenic sesquiterpene (73) which is related to an acyclic compound previously reported from this source.

2.5 Biosynthesis of Acetylenic Compounds. – Only one report of a biosynthetic study has appeared during the two year period covered by this report. Labelling studies of the biosynthesis of the thiophenes (74) and (75) in Tagetes patula used tritium labelled (76) – (81), with the label at both the β positions of the thiophene rings. The results, based on the relative incorporation of the precursors into (82), (74) and (75) are sununarised in Scheme 1. It is probable that there are two routes operating in T. patula. Route (A) leads the bithiophenylbutynol (74) while route (B) leads to the terthiophene (75). The possibility of (82) as an intermediate can not be excluded. The involvement of (77) and (81), not so far detected in nature, is supported by the previous isolation of (83) from T. erecta.

2.6 Physiological Properties of Polyacetylenic Compounds. – The role of polyacetylenes as phytoalexins (plant defence substances) has received considerable attention. The isolation of falcarinol, falcarindiol and (17) from Lycopersicon esculentum inoculated with Cladosporium fulvum has already been mentioned. The maximum concentrations of falcarindiol and (17) were 5-10 µg g-1 fresh weight. Mycelial growth of C. fluvum and C. cucumerinum was completely inhibited in vitro by 6 and 18 µg ml-1 of falcarindiol and (17) respectively. The mechanism of the antifungal action of falcarindiol has been investigated. It is suggested that it acts on the plasma membrane of the fungus or affects some process needed for membrane function. The occurrence and accumulation of falcarinol in the induced resistance response of carrot root slices to Botrytis cinerea is reported.

A study of the changes in concentration of seven wyerone derivatives in the bean Vicia faba (Leguminosae) undergoing resistant reactions to B. cinerea or B. faba used h.p.l.c. to monitor the concentrations. The proportion of monitor the concentrations. The proportion of dihydro compounds varied in different tissues and with the time after inoculation, but they were always at lower levels than their more unsaturated analogues. Wyerone derivatives are toxic to the leaves of V. faba at lower levels than those produced in response to Botrytis infection, and may be the primary cause of leaf death after fungal infection. The lower sensitivity of B. faba compared with B. cinerea to wyerone derivatives in vitro is reported. The ability of B. faba to survive exposure to phytoalexins may contribute to its greater pathogenicity under field conditions. A genetical approach to this difference in pathogenicity between the Botrytis species also revealed differences in phytoalexin sensitivity. Wyerone is among the most toxic of a number of phytoalexins towards gram positive bacteria.

The previously reported dichotomy in the phytoalexin response among the genera of the tribe Vicieae (Leguminosae) has been amply confirmed by a study of over sixty species. Those of the genera Vicia and Lens produce furanoacetylenes on infection while those of the genera Pisum and Lathyrus produce the pterocarpan pisatin and related compounds.

Cis and trans matricaria ester derivatives and cis lachnophyllum ester are produced by the roots of four Erigeron species and cis matricaria ester is produced by the roots of Solidago altissima. These compounds are allelopathic, inhibiting germination and growth of other species, and are of ecological significance in the succession of plants colonising disturbed ground.

The phototoxic effects of naturally occurring polyacetylenes and α-terthienyl have been further studied by Wat, Towers, Lam, and co-workers. Hernolysis, potassiwn ion leakage, and acetylcholinesterase inhibition were produced by these compounds in hwnan erythrocytes, the effect being enhanced by long wave-length U.V. light. Falcarindiol is non-phototoxic but causes hemolysis in the dark. Polyacetylenes from the Asteraceae have been tested on a number of organisms. Some of these compounds are phototoxic to a number of invertebrates, and a detailed study of their potential use as mosquito larvicides is reported. These compounds are also phototoxic towards marine and freshwater algae, triacetylenes being more toxic than diacetylenes, and a small number of polyacetylenes with terminal alcohol or aldehyde functions were found to be toxic even without U.V. irradiation.

Polyacetylenes and α-terthienyl have been assessed for their ability to produce chromosome damage. Despite previous reports to the contrary, chromosome damage was not found to accompany their phototoxic effects – a matter of some relief to gardeners and encouraging for the use of such compounds as pesticides and topical antibiotics.

3 Natural Olefinic Compounds

This part of the review covers those long chain olefinic compounds which do not obviously fall within any other compound class. While some have structural and possible biosynthetic features in common with the foregoing acetylenic compounds, the majority are related only by an aliphatic chain of some length.

3.1 Isolation.- The amides (84) – (86) occur in Leuocyclus formosus and (87) occurs in Achillea crithmifolia. The related acetylenic amides from A. tomentosa have already been described. The olefinic γ-lactones from Clinostemon mahuba (previously known as Licaria mahuba) have now been fully reported.

The epoxide (88), derived from aplotaxene (89),occurs in Cirsium hypoleucum. The stereochemistry of the epoxide could not be determined from the spectral data, but it is suggested that it is cis on biosynthetic grounds.

A number of olefinic compounds containing two or more conjugated double bonds have been reported. The unusual crypto-caryic and arnygdalinic acids (90) and (91) occur in Cryptocarya amygdalina. These structures follow from n.m.r. and mass spectral data and consideration of the least strained structure compatible with the formula of the alicyclic portion of the molecule. A novel methyl substituted polyene (92) has been isolated from the mycelium of Penicillium pedemontanum. This structure was based on high resolution p.m.r. spectra using shift reagents, and mass spectral data. Streptomyces aureofaciens produces a number of hypotensive vasodilators. One of these, WS-1228A, has been shown to be a long chain polyene with a novel triazene function (93). The double bond pattern was confirmed by synthesis of the corresponding aldehyde from which (93) was prepared (see below).

The hydroxyenal (94) was isolated from Liagora fariosa along with the acetylenes previously described. It is also toxic to Eupomacentrus leucostictus. Two aliphatic esters (95) and (96) are among the complex mixture of minor components of origanum oil (Cardiothymus capitatus).

3.2 Synthesis. – WS-1228A (93) was synthesised by the route shown in Scheme 2. The first of the conjugated trans double bonds was inserted by a standard copper catalysed coupling of trans-hexenyl bromide and propargyl tetrahydropyranyl ether, followed by reduction with sodium in liquid ammonia. The second conjugated double bond was formed by a Wittig reaction, after which the aldehyde (97) was prepared and was identical with the aldehyde obtained from natural (93). Synthetic (93) prepared from (97) was identical with the natural product.

Two new syntheses of alkenyl phenols are reported. The pentadecenyl catechol (98) is one of a group of compounds collectively known as ursinols which form the vesicant principle of poison ivy. Previous syntheses of (98) are not satisfactory. The new synthesis (Scheme 3) uses a lithium exchange reaction on 1,2-dimethylbenzene to give a product lithiated predominantly at position 3. The side chain is then elaborated by standard reactions. Semi-hydrogenation of the acetylenic intermediate was unsatisfactory with Lindlar catalyst but proceeded well with the Schneider catalyst (palladium-barium sulphate in pure, dry pyridine).

The alkenyl-resorcinols (99) and (100), which are constituents of cashew nut oil, have now been synthesised. The conunon intermediate (101) was prepared by addition of 3,5-dimethoxybenzaldehyde and protected 6-chlorohexan-1-ol to lithium at low temperature, followed by standard reactions, and the olefinic chains then elaborated as shown in Scheme 4. The semi-hydrogenation again used palladium-barium sulphate catalyst.

(Continues…)Excerpted from Aliphatic and Related Natural Product Chemistry Volume 3 by F. D. Gunstone. Copyright © 1983 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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