Aliphatic alcohols occur
naturally in free form (component of the cuticular lipids) but more usually in esterified
(wax esters) or etherified form (glyceryl ethers). Several alcohols belong to aroma
compounds which are found in environmental or food systems (see the website: Flavornet).
They are found with normal, branched (mono- or isoprenoid), saturated or unsaturated of
various chain length and sometimes with secondary or even tertiary alcoholic function.
An unusual phenolic alcohol is found as a component of
glycolipids in Mycobacteria. Some cyclic alcohols have
been described in plants.
A classification according to the carbon-chain structure is given below.
The carbon chain may be fully saturated or unsaturated (with double and/or triple bonds), it may also be substituted with chlorine, bromine or sulfate groups. Some acetylenic alcohols have been also described.
-
Saturated alcohols
Among the most common, some are listed below
Formula |
Normal alcohols |
Iso-alcohols |
Anteiso-alcohols |
C12H25OH |
1-dodecanol |
10-methyl-1-hendecanol |
9-methyl-1-hendecanol (anteisolauryl alcohol) |
C14H29OH |
1-tetradecanol |
12-methyl-1-tridecanol |
11-methyl-1-tridecanol (anteisomyristyl alcohol) |
C16H33OH |
1-hexadecanol |
14-methyl-1-pentadecanol (isopalmityl alcohol) |
13-methyl-1-pentadecanol (anteisopalmityl alcohol) |
C18H37OH |
1-octadecanol |
16-methyl-1-heptadecanol (isostearyl alcohol) |
15-methyl-1-pentadecanol (anteisostearyl alcohol) |
Free fatty alcohols are not commonly found in epicuticular lipids of
insects, although high molecular weight alcohols have been reported in
honeybees (Blomquist GJ et al., Insect
Biochem 1980, 10, 313). Long-chain
alcohols also have been reported in the defensive secretions of scale
insects (Byrne DN et al., Physiol Entomol 1988, 13,267). Typically,
insects more commonly produce lower molecular weight alcohols. Honeybees
produce alcohols of 17–22 carbons, which induce arrestment in parasitic
varroa mites (Donze G et al., Arch Insect Biochem Physiol 1998, 37, 129).
Two female-specific fatty alcohols, docosanol (C22) and eicosanol (C20),
which have been found in epicuticle of Triatoma infestans (a vector
of Chagas disease in South America), are able to trigger copulation in males
(Cocchiararo-Bastias L et al., J Chem Ecol 2011, 37, 246). Hexadecyl
acetate is found in the web of some spiders (Pholcidae) to attract females (Schulz
S, J Chem Ecol 2013, 39, 1).
Long-chain alcohols (C18, C24, C28) from the femoral glands in the male
lizard Acanthodactylus boskianus play a role in chemical
communication as a scent marking pheromone (Khannoon ER et al.,
Chemoecology 2011, 21, 143).
Various fatty alcohols are found in the waxy film
that plants have over their leaves and fruits. Among them, octacosanol (C28:0) is
the most frequently cited.
Policosanol is a natural mixture
of higher primary aliphatic alcohols isolated and purified from sugar cane (Saccharum
officinarum, L.) wax, whose main component is octacosanol but contains
also hexacosanol (C26:0) and triacontanol or melissyl alcohol (C30:0).
Policosanol is also extracted from a diversity of other natural sources such
as beeswax, rice bran, and wheat germ (Irmak S et al., Food Chem 2006,
95, 312) but is also present in the fruits, leaves, and surfaces of
plants and whole seeds. A complex policosanol mixture has been identified in
peanut (Cherif AO et al., J Agric Food Chem 2010, 58, 12143). More
than 20 aliphatic alcohols were identified (C14-C30) and four unsaturated
alcohols (C20-24). The total policosanol content of the whole peanut samples
varied from 11 to 54 mg/100 g of oil.
This mixture was shown to have
cholesterol-lowering effects in rabbits
(Arruzazabala ML et al., Biol Res 1994,
27, 205).
Octacosanol was also able to suppress lipid accumulation in rats fed on a high-fat
diet (Kato
S et al., Br J Nutr 1995, 73, 433)
and to inhibit platelet aggregation (Arruzazabala
ML et al., Thromb Res 1993, 69, 321).
The effectiveness of policosanol is still questionable but it has been approved
as a cholesterol-lowering drug in over 25 countries (Carbajal
D et al., Prostaglandins Leukotrienes Essent Fatty Acids 1998, 58, 61),
and it is sold as a lipid-lowering supplement in more than 40 countries. More recent studies in
mice question about any action on improvement of lipoprotein profiles (Dullens
SPJ et al., J Lipid Res 2008, 49, 790). The authors conclude that
individual policosanols, as well as natural policosanol mixtures,
have no potential for reducing coronary heart disease risk through
effects on serum lipoprotein concentrations. Furthermore, sugar cane
policosanol at doses of 20 mg daily has shown no lipid lowering effects in
subjects with primary hypercholesterolemia (Francini-Pesenti
F et al., Phytother
Res 2008, 22,
318). It must be
noticed that, for the most part, positive results have been obtained by only one
research group in Cuba. Outside Cuba, all groups have failed to validate the
cholesterol-lowering efficacy of policosanols (Marinangeli C et al., Crit Rev
Food Sci Nutr 2010, 50, 259). Independent studies are required before
evaluating the exact value of the therapeutic benefits of that mixture.
An
unsaturated analogue of octacosanol, octacosa-10, 19-dien-1-ol was
synthesized and was as effective as policosanol in inhibiting the
upregulation of HMGCoA reductase (Oliaro-Bosso S et al., Lipids 2009, 44,
907). This work opens promising perspectives for the design of new
antiangiogenic compounds (Thippeswamy
G et al., Eur J Pharmacol 2008, 588, 141). An
unsaturated analogue of octacosanol, octacosa-10, 19-dien-1-ol was
synthesized and was as effective as policosanol in inhibiting the
upregulation of HMGCoA reductase (Oliaro-Bosso S et al., Lipids 2009, 44,
907). This work opens promising perspectives for the design of new
antiangiogenic compounds.
1-Octanol and 3-octanol are components of the
mushroom flavor (Maga JA, J Agric Food Chem 1981, 29, 1).
Many alcohols in the C10 to C18 range, and their short-chain acid esters are
potent sex or aggregation pheromones. They are mainly found as components of
specialized defensive glands, pheromone glands or glands of the reproductive
system.
A series of C22 up to C28 saturated n-alcohols, with even carbon numbers
predominating, and a maximum at C26 and C28, has been identified in the
cyanobacterium Anabaena cylindrica (Abreu-Grobois FA et al.,
Phytochemistry 1977, 16, 351). Several authors have reported high contents
of the 22:0 alcohol in sediments where an algal origin is plausible. For
example, the major alcohol in a sample of the lacustrine Green River Shale of
Eocene age is also 22:0 which comprises over 50% of the alcohols present
(Sever JR et al., Science 1969, 164, 1052)
Long-chain alcohols are known as major surface lipid components
(waxes) with chains from C20 up to C34 carbon atoms, odd carbon-chain alcohols
being found in only low amounts. Very long-chain methyl-branched
alcohols (C38 to C44) and their esters with short-chain acids were shown to be
present in insects, mainly during metamorphosis. A
series of long-chain alkanols (more than 23 carbon atoms) were identified in
settling particles and surface sediments from Japanese lakes and were shown to
be produced by planktonic bacteria being thus useful molecular markers (Fukushima
K et al., Org Geochem 2005, 36, 311).
Cutin and suberin contain as monomer saturated alcohols from C16 to C22 up
to 8% of the total polymers. C18:1 alcohol
(oleyl alcohol) is also
present.
Long-chain di-alcohols
(1,3-alkanediols) have been described in the waxes which impregnate the matrix
covering all organs of plants (Vermeer CP et al., Phytochemistry 2003, 62,
433). These compounds forming about 11% of the leaf cuticular waxes of Ricinus
communis were identified as homologous unbranched alcohols ranging from C22
to C28 with hydroxyl group at the carbon atoms 1 and 3.
In the leaf cuticular waxes of Myricaria germanica (Tamaricaceae) several
alkanediols were identified (Jetter R, Phytochemistry 2000, 55, 169).
Hentriacontanediol (C31) with one hydroxyl group in the 12-position and the
second one in positions from 2 to 18 is the most abundant diol (9% of the wax).
Others were far less abundant : C30-C34 alkanediols with one hydroxyl group on a
primary and one on a secondary carbon atom, C25-C43 b-diols
and C39-C43 g-diols.
Very-long-chain 1,5-alkanediols ranging from C28 to C38, with strong
predominance of even carbon numbers, were identified in the cuticular wax of Taxus
baccata (Wen M et al., Phytochemistry 2007, 68, 2563). The
predominant diol had 32 carbon atoms (29% of the total).
Long-chain saturated C30-C32 diols
occur in most marine sediments and in a few instances, such as in Black Sea
sediments, they can be the major lipids (de Leeuw JW et al., Geochim
Cosmochim Acta 1981, 45, 2281). A microalgal source for these compounds was
discovered when Volkman JK et al. (Org Geochem 1992, 18, 131) identified
C30-C32 diols in marine eustigmatophytes from the genus Nannochloropsis.
Two nonacosanetriols (7,8,11-nonacosanetriol and 10,12,15-nonacosanetriol) have
been isolated from the outer fleshy layer (sarcotesta) of the Ginkgo biloba
"fruit" (Zhou
G et al., Chem Phys Lipids 2012, 165, 731). They exhibited slight
activity of antithrombin and moderate activities of platelet aggregation in
vitro.
The chief lipid fraction in the uropygial gland excretion of the domestic
hen is a diester wax. The unsaponifiable fraction consists of a series
of three homologous compounds, which have been named the uropygiols
and identified as 2,3-alkanediols containing 22-24 carbon atoms. These
fatty alcohols are esterified by saturated normal C22-C24 fatty acids (Haahti
E et al., J Lipid Res 1967, 8, 131).
- Unsaturated alcohols
Some fatty alcohols have one double bond (monounsaturated). Their general
formula is:
CH3(CH2)xCH=CH(CH2)y-CH2OH
The unique double bond may be found in different positions: at the C6: i.e. cis-6-octadecen-1-ol (petroselenyl alcohol), C9 i.e cis-9-octadecen-1-ol
(oleyl alcohol) and C11 i.e cis-11-octadecen-1-ol (vaccenyl alcohol). Some of these alcohols have insect pheromone activity.
As an example, 11-eicosen-1-ol is a major component of the alarm pheromone
secreted by the sting apparatus of the worker honeybee. In zooplankton, the
cis-11-docosen-1-ol (22:1 (n-11) alcohol) is not only present in high
proportion in wax esters (54 to 83%) but may be also predominant in free
form (75-94% of free alcohols) in ctenophores (Graeve M et al., Mar Biol
2008, 153, 643). This presence is unexplained because pathways for
conversion and catabolism of fatty alcohols in ctenophores are still
unknown.
Some short-chain unsaturated alcohols are components of mushroom flavor,
such as 1-octen-3-ol,
t2-octen-1-ol, and c2-octen-1-ol
(Maga JA, J Agric Food Chem 1981, 29, 1).
An acetoxy derivative of a 16-carbon alcohol with one double bond, gyptol
(10-acetoxy cis-7-hexadecen-1-ol), was described to be a strong attractive
substance secreted by a female moth (Porthetria dispar, "gypsy moth").
A fatty alcohol with two double bonds, bombykol (tr-10,cis-12-hexadecadien-1-ol),
was also shown to be excreted as a very strong attractive substance by the
female of silk-worm (Bombyx mori).
This first discovery of a pheromone
was made by Butenandt A et al. (Z Naturforsch 1959, 14, 283) who was
formerly Nobel laureate (in 1939) for his work in sex hormones. Another pheromone,
8,10-dodecadienol (codlemone), is secreted by the codling moth Cydia
pomonella, has been used for monitoring and mating in apple and pear
orchards in the USA and Europe. This molecule was also used to monitor the
population of the pea moth Cydia nigricana. Likewise, 7,9-dodecadienol,
the female pheromone of the European grapewine moth Lobesia botrana, was
used to control this important pest in vineyards.
A fatty triol with one double bond, avocadene
(16-heptadecene-1,2,4-triol) is found in avocado fruit (Persea americana)
and has been tested for anti-bacterial and anti-inflammatory properties. These
properties are likely related with the curative effects of avocado described for
a number of ailments (diarrhea, dysentery, abdominal pains and high blood
pressure). Several others heptadecanols with one primary and two secondary
alcohol functions and with one double or triple bond have been identified in
the leaves of Persea americana (Lee TH et al., Food Chem 2012,
132, 921). One or two of these alcohol groups may be acetylated. These
compounds may be related to the known antifungal activity of Persea
leaves.
Long-chain alkenols (C37 to C39) with 2 to 4 double bonds, the reduced form of
the alkenones, have been described in the benthic
haptophyte Chrysotila lamellosa (Rontani JF et al., Phytochemistry
2004, 65, 117). al., 1986). C30 to C32 alcohols having one or two double
bonds are significant constituents of the lipids of marine eustigmatophytes of
the genus Nannochloropsis (Volkman JK et al., Org Geochem 1992, 18,
131). These microalgae could be partially the source of the
alkenols found in some marine sediments.
Long-chain
Bruchin A
Two chlorinated derivatives of unusual alcohols were described in a red alga Gracilaria verrucosa (Shoeb M et al., J Nat Prod 2003, 66, 1509). Both compounds have a C12 aliphatic chain chlorinated in position 2 and with one double bond at carbon 2 (compound 1 : 2-chlorododec-2-en-1-ol) or two double bonds at carbon 2 and 11 (compound 2 : 2-chlorododec-2,11-dien-1-ol).
- Acetylenic alcohols
Natural acetylenic alcohols and their derivatives have been isolated from a
wide variety of plant species, fungi and invertebrates. Pharmacological studies
have revealed that many of them display chemical and medicinal properties.
Monoacetylenic alcohols
: were isolated from culture of Clitocybe catinus
(Basidiomycetes) and the study of their structure revealed the presence of two
or three hydroxyl groups (Armone A et al., Phytochemistry 2000, 53, 1087).
One of these compounds is shown below.
Acetylenic alcohols have been also described in a tropical sponge Reniochaline sp (Lee HS et al., Lipids 2009, 44, 71). One of the two described in that species is shown below, it exhibited a significant growth effect against human tumor cell lines.
Polyacetylenic alcohols : Several examples
with different chain lengths,
unsaturation degrees, and substitution have been reported from terrestrial
plants and marine organisms. Food plants of the Apiaceae (Umbellifereae) plant
family such as carrots, celery and parsley, are known to contain several
bioactive bisacetylenic alcohols. The main plant sources of these compounds are Angelica
dahurica, Heracleum sp and Crithmum maritimum (falcarindiol,
falcarinol), red ginseng (Panax ginseng) (panaxacol, panaxydol, panaxytriol), Cicuta
virosa (virol A), and Clibadium sylvestre (cunaniol). All these
compounds display antibiotic or cytotoxic activities.
Polyacetylenes have been isolated from the stems of Oplopanax elatus
(Araliaceae), plant used in Korean and Chinese traditional medicine for
anti-inflammatory and analgesic purposes (Yang MC et al., J Nat Prod 2010,
73, 801). Among the most efficient in inhibiting the formation of nitric
oxide in LPS-induced cells is a seventeen-carbon diyne diol with an epoxy cycle,
oploxyne A. Other parent compounds without the epoxy group were also described.
Falcarinol, a seventeen-carbon diyne fatty
alcohol (1,9-heptadecadiene-4,6-diyn-3-ol), was first isolated from Falcaria
vulgaris (Bohlmann F et al., Chem Ber 1966, 99, 3552) as well as from
Korean ginseng (Takahashi et al., Yakugaku Zasshi 1966, 86, 1053).
It was also isolated from carrot (Hansen SL
et al.
Falcarinol protects the
vegetable from fungal diseases, it showed biphasic activity, having stimulatory
effects between 0.01 and 0.05 µg per ml and inhibitory effects between 1 and 10
µg per ml, whereas b-carotene
showed no effect in the concentration range 0.001–100 µg per ml (Hansen SL
et al., J Sci Food Agric 2003, 83, 1010). Experiments with
macrophage cells have shown that falcarinol (and its C-8 hydroxylated
derivative, falcarindiol) reduced nitric oxide production, suggesting that these
polyacetylenes are responsible for anti-inflammatory bioactivity (Metzger
BT et al., J Agric Food Chem 2008, 56, 3554). Falcarindiol was first
reported as phytochemicals in carrots (Daucus carota) (Bentley RK et
al., J Chem Soc 1969, 685). Besides falcarinol, falcarindiol, and
falcarindiol 3-acetate, nine additional bisacetylene alcohols were identified in
Daucus carota (Schmiech L et al., J Agric Food Chem 2009, 57, 11030).
Experiments with human
intestinal cells demonstrate that aliphatic C17-polyacetylenes (panaxydol,
falcarinol, falcarindiol) are potential anticancer principles of carrots and
related vegetables (parsley, celery, parsnip, fennel) and that synergistic
interaction between bioactive polyacetylenes may be important for their
bioactivity (Purup S et al., J Agric Food Chem 2009, 57, 8290). Compounds
very similar to falcarinol and extracted from Panax japonicus are potent
a-glucosidase inhibitors (Chan
HH et al., Phytochemistry 2010, 71, 1360). These inhibitors may
potentially reduce the progression of diabetes by decreasing digestion and
absorption of carbohydrates.
The water dropwort (Oenanthe crocata), which lives near streams in the
Northern Hemisphere, contains a violent toxin, cicutoxin, resulting in
convultions and respiratory paralysis (Uwai K et al., J Med Chem 2000, 43,
4508).
The biochemistry and bioactivity of polyacetylenes are presented in a review (Christensen
LP et al., J Pharm Biomed Anal 2006, 41, 683) as well methods for the
isolation and quantification of these compounds.
Many other polyacetylenic alcohols were found in primitive marine organisms,
such as sponges and ascidians. These invertebrates have no physical defenses and
thus they have developed efficient chemical mechanisms such as polyacetylenic
metabolites to resist predators and bacteria.
A C36 linear diacetylene alcohol
named lembehyne was found in an Indonesian marine sponge (Haliclona sp) (Aoki
S et al., Tetrahedron 2000, 56, 9945) and was later able to induce neuronal
differentiation in neuroblastoma cell (Aoki S et al., Biochem Biophys Res
Comm 2001, 289, 558).
Several polyacetylenic alcohols with 22 carbon atoms were isolated and identified in lipid extract from a Red Sea sponge, Callyspongia sp (Youssef DT et al., J Nat Prod 2003, 66, 679). Their physical study revealed the presence of 4 triple bonds and one, two or three double bonds. The structure of one of these Callyspongenols is given below.
Several di- and
tri-acetylenic di-alcohols with a chain of 26 up to 31 carbon atoms, named strongylodiols,
have been isolated from a Petrosia Okinawan marine sponge (Watanabe K
et al., J Nat Prod 2005, 68, 1001). Some of them have cytotoxic
properties.
Several
polyacetylenic alcohols with 21 carbon atoms were isolated from a marine
ascidian (Polyclinidae) and were determined to have two triple bonds
combined with a conjugated dienyne group (Gavagnin M et al., Lipids 2004, 39,
681). Some of them have an additional hydroxyl group or only three double
bonds. The structure of one of these
molecules is
given below.
Several brominated polyacetylenic diols with cytotoxic properties were isolated from a Philippines sponge Diplastrella sp (Lerch ML et al., J Nat Prod 2003, 66, 667). One of these molecules is shown below.
A comprehensive survey of acetylenic alcohols in plant and invertebrates with information on their anticancer activity has been released by Dembitsky VM (Lipids 2006, 41, 883).
Long-chain di-hydroxy alcohols in which both the primary and secondary hydroxyl groups are converted to sulfate esters and one to five chlorine atoms are introduced at various places have been discovered in the alga Ochromonas danica (Chrysophyceae, Chrysophyta) where they constitute 15% of the total lipids (Haines TH, Biochem J 1969, 113, 565). An example of these chlorosulfolipids is given below. There may be several types of chlorine addition : one at R4, two at R3 and R5 or R1 and R2, five at R1 to R5 and six at R1 to R6.
Similar molecules with a 24 carbon
chain was also described in Ochromonas malhamensis (review in Dembitsky
VM et al., Prog Lipid Res 2002, 41, 315 and in Bedke DK et
al., Nat Prod Rep 2011, 28, 15). It was suggested that the
chlorosulfolipids replace sulfoquinovosyl diglyceride, since when the later is
high the former is low and vice versa. They have been associated with the human
toxicity of the mussel-derived lipids (Diarrhetic Shellfish Poisoning).
Several of these chlorosulfolipids
have also been identified from more than 30 species of both freshwater and
marine algae belonging to green (Chlorophyceae), brown (Phaeophyceae),
red (Rhodophyceae) macrophytic algae (Mercer EI et al., Phytochemistry
1979, 18, 457), and other microalgal species (Mercer EI et al.,
Phytochemistry 1975, 14, 1545).
Some fatty alcohols, such as dodecanol (lauryl or dodecyl alcohol), are used for
the manufacture of detergents after sulphonation (by action of SO3 gas). The
salt sodium laurylsulfate (or sodium dodecylsulfate) is a detergent and strong
anionic surfactant, used in biochemistry and in the composition of cosmetic
products (shampoos, toothpastes).
-
Mono-methylated alcohols
In 1936, Stodola et al. characterized an optically active substance recovered on saponification of ‘‘purified waxes’’ of Mycobacterium tuberculosis, determined its global formula and proposed to name it phthiocerol (Stodola FH et al., J Biol Chem 1936, 114, 467). In 1959, after several chemical studies, its structure was determined as a mixture of C36 and C34
b-glycols. It has been proposed that the term phthiocerol be reserved for the original 3-methoxy congener (phthiocerol A) and that the term phthioglycol be used to refer to the family of compounds (Onwueme KC et al., Prog Lipid Res 2005, 44, 259).
Among the most important saturated isopranols found in plants or in geological sediments are those having two (tetrahydrogeraniol), three (farnesanol), or four (phytanol) isoprenoid units. Pristanol (2,6,10,14-tetramethyl-1-pentadecanol) is tetramethylated but with only three complete isoprenoid units.
B - Unsaturated polyisoprenoids (prenols
or polyprenols)
They have the following general structure :
These molecules consist of several up to more than 100 isoprene residues linked head-to-tail, with a hydroxy group at one end (
a-residue) and a hydrogen atom at the other (w-end).- 1. all trans forms : They have the following structure:
trans-Polyprenol
Some important members of the series are as follows:
| n | Number of isoprene unit |
Number of carbons |
Name |
| 0 | 2 |
10 |
Geraniol |
| 1 | 3 |
15 |
Farnesol |
| 2 | 4 |
20 |
Geranylgeraniol |
| 3 | 5 | 25 | Geranylfarnesol |
| 7 | 9 | 45 | Solanesol |
| 8 |
10 |
50 |
Spadicol |
Long-chain trans-polyprenol (n>8) have been
characterized from Eucommia ulmoides.
Geraniol (from rose oil) is a monoterpene (2
isoprene units). It has a rose-like odor and is commonly used in perfumes and as
several fruit flavors. Geraniol is also an effective mosquito repellent.
Inversely, it can attract bees as it is produced by the scent glands of honey
bees to help them mark nectar-bearing flowers and locate the entrances to their
hives.
Farnesol is a sesquiterpene
(3 isoprene units). It is the prenol that corresponds to the carbon skeleton of the simplest juvenile
hormone described for the first time in insects in 1961 (Schmialek PZ, Z
Naturforsch 1961, 16b, 461; Wigglesworth VB, J Insect Physiol 1961, 7, 73). It
is present in many essential oils such as citronella, neroli, cyclamen, lemon
grass, rose, and others. It is used in perfumery to emphasize the odors of sweet
floral perfumes. It is especially used in lilac perfumes. As a pheromone, farnesol
is a natural pesticide for mites. The dimorphic fungus Candida albicans
has been shown to use farnesol as quorum-sensing molecule (Hornby
JM et al., Appl Environ Microbiol 2001, 67, 2982).
Geranylgeraniol is a diterpene (4 isoprene units). Geraniol and geranylgeraniol are important molecules in the synthesis of various terpenes, the acylation of
proteins and the synthesis of vitamins (Vitamins E and K).
The covalent addition of phosphorylated derivatives of typical isoprenoids,
farnesyl pyrophosphate and geranylgeranyl pyrophosphate, to proteins is a
process (prenylation) common to G protein subunits. These isoprenylated proteins
have key roles in membrane attachment leading to central functionality in cell
biology and pathology.
Solanesol, discovered in tobacco leaves in
1956 (Rowland RL et al., J Am Chem Soc 1956, 78, 4680), may be an
important precursor of the tumorigenic polynuclear aromatic hydrocarbons of smoke but is
also a possible side chain for plastoquinone. Solanesol is also present in the
leaves of other Solanaceae plants including tomato, potato, eggplant and pepper.
It has useful medicinal properties and is known to possess anti-bacterial,
anti-inflammation, and anti-ulcer activities (Khidyrova NK et al., Chem Nat
Compd 2002, 38, 107). Industrially, solanesol is extracted from Solanaceae
leaves (about 450 tons in 2008) and used as an intermediate in the synthesis of
coenzyme Q10 and vitamin K analogues.
Spadicol was discovered in the spadix (inflorescence) of the Araceae Arum
maculatum (Hemming FW et al., Proc R Soc London 1963, 158, 291). Its
presence is likely related to its presence in the ubiquinone as the side-chain.
Phytol is a partially saturated diterpene, a monounsaturated derivative of geranylgeraniol which is part of the chlorophyll molecule :
- 2. ditrans-polycis-prenols, such as the bacteria prenol and
betulaprenol types.
In general, bacteria, as all prokaryotic cells, possess ditrans-polycis-prenols
containing between 10 and 12 units, the most abundant being undecaprenol (trivial name
bactoprenol).
Bacteriaprenol type
Betulaprenols with n = 3-6 were
isolated from the woody tissue of Betula verrucosa (Wellburn AR et
al., Nature 1966, 212, 1364), and bacterial polyprenol with n = 8 were
isolated from Lactobacillus plantarum (Gough DP et al., Biochem J
1970, 118, 167). Betulaprenol-like species with 14 to 22 isoprene units have
been discovered in leaves of Ginkgo biloba (Ibata K et al., Biochem J
1983, 213, 305).
Polyisoprenoid alcohols are accumulated in
the cells most often as free alcohols and/or esters with carboxylic acids. A
fraction of polyisoprenoid phosphates has also been detected, and this form
is sometimes predominant in dividing cells and Saccharomyces cerevisiae
(Adair WL et al., Arch Biochem Biophys 1987, 259, 589).
- 3. tritrans-polycis-prenols, of the ficaprenol type.
Some of the earliest samples were obtained from Ficus elastica, giving rise to the trivial names ficaprenol-11 and ficaprenol-12 (Stone KJ et al. Biochem J 1967, 102, 325).
Ficaprenol type
In plants, the diversity of polyprenols is much broader, their chain length covers the broad spectrum of compounds ranging from 6 up to 130 carbon atoms (Rezanka T et al., J Chromatogr A 2001, 936, 95).
- 4. dolichol types, the a
terminal is saturated.
Most eukaryotic cells contain one type of polyisoprenoid alcohols with one a-saturated
isoprenoid unit (2,3-dihydro polycis-prenols) which have been called dolichol
by Pennock JF et al. (Nature 1960, 186, 470), a derivative of prenols. Most
of these carry two trans units at the
w-end of
the chain.
Dolichols (fro the Greek dolikos: long) have the general structure :
Dolichols isolated from yeast or
animal cells consist mainly of seven to eight compounds, those with 16, 18, or
19 isoprenoid units being the most abundant (Ragg SS, Biochem Biophys Res
Comm 1998, 243, 1).
Dolichol amount was shown to be increased in the brain gray matter of elderly (Pullarkat RK
et al., J Biol Chem 1982, 257, 5991). Dolichols with 19, 22 and 23
isoprenoid units were described as early as 1972 in marine invertebrates (Walton
MJ et al., Biochem J 1972, 127, 471). Furthermore, the pattern of their distribution may be
considered as a chemotaxonomic criterion. It has been reported that a high
proportion of dolichols is esterified to fatty acids. As an example, 85-90% of
dolichols are esterified in mouse testis (Potter
J et al., Biochem Biophys Res Comm 1983, 110, 512). In addition, dolichyl
dolichoate has been found in bovine thyroid (Steen
L. et al., Biochim Biophys Acta, 1984, 796, 294).
They are well known for their important role as
glycosyl carrier in a phosphorylated
form in the
synthesis of polysaccharides and glycoproteins in yeast cells, and animals.
Dolichyl phosphate is an obligatory intermediate in the biosynthesis of N-glycosidically
linked oligosaccharide chains. Conversely, they have been identified as the predominant
isoprenoid form in roots (Skorupinska-Tudek
K et al., Lipids 2003, 38, 981) and in mushroom tissue (Wojtas
M et al., Chem Phys Lipids 2004, 130, 109). Similar compounds (ficaprenols)
have the same metabolic function in plants.
The repartition of the various types
of polyisoprenoid alcohols between plants and animals and their metabolism have been extensively
discussed (Swiezewska E et al., Prog Lipid Res 2005, 44, 235).
Biosynthesis of polyisoprenoid alcohols and their biological
role have been reviewed in 2005 (Swiezewska E et al., Prog Lipid Res 2005,
44, 235).
3 - Phenolic
alcohols
Among the simple phenolic alcohols, monolignols are the source materials for biosynthesis of both lignans and lignin. The starting material for production of monolignols (phenylpropanoid) is the amino acid phenylalanine. There are two main monolignols: coniferyl alcohol and sinapyl alcohol. Para-coumaryl alcohol is similar to conipheryl alcohol but without the methoxy group.
Conipheryl alcohol is found in both gymnosperm and angiosperm
plants. Sinapyl alcohol and para-coumaryl alcohol, the other two lignin
monomers, are found in angiosperm plants and grasses. Conipheryl esters (conypheryl
8-methylnonanoate) have been described in the fruits of the pepper, Capsicum
baccatum (Kobata K et al., Phytochemistry 2008, 69, 1179). These
compounds displayed an agonist activity for transient receptor potential
vanilloid 1 (capsaicin receptor) as the well known capsaicinoids present in
these plant species.
Complex phenolic alcohols (phenolphthiocerol)
were shown to be
components of Mycobacterium glycolipids which are termed glycosides of
phenolphthiocerol dimycocerosate (Smith DW et al., Nature 1960, 186, 887)
belonging to the large family of "mycosides". The chain length differs
according to the homologues, 18 and 20 carbon atoms in mycosides
A, and B, respectively. One of these phenolphthiocerols is shown
below.
An analogue component but with a ketone group instead of the methoxy group, a phenolphthiodiolone, has been detected in mycoside A (Fournie JJ et al., J Biol Chem 1987, 262, 3174).
4
-
Cyclic
alcohols
An alcohol with a furan group, identified as
3-(4-methylfuran-3-yl)propan-1-ol, has been isolated from a fungal endophyte
living in a plant, Setaria viridis (Nakajima H et al., J Agric Food
Chem 2010, 58, 2882). That compound was found to have a repellent effect on
an insect, Eysarcoris viridis, which is a major pest of rice.
3-(4-methylfuran-3-yl)propan-1-ol
Some cyclic alkyl polyols have been reported
in plants. Among the various form present in an Anacardiaceae, Tapirira
guianensis, from South America, two displayed anti-protozoal (Plasmodium
falciparum) and anti-bacterial (Staphylococcus spp) activities (Roumy
V et al., Phytochemistry 2009, 70, 305). The structure shown below is
that of a trihydroxy-alcohol containing a cyclohexene ring.
4,6,2'-trihydroxy-6-[10'(Z)-heptadecenyl]-1-cyclohexen-2-one
As emphasized by the
authors, external application of the active plant extract or of the
purified compounds could represent an accessible therapeutic alternative to
classical medicine against leishmaniasis.
Long-chain
aldehydes are found in free form, but also in the form of vinyl ether (known as alk-1-enyl
ether) integated in glycerides and phospholipids (plasmalogens).
The free aldehydes can be as fatty acids saturated or unsaturated. They have a general
formula CH3(CH2)nCHO with n=6 to 20 or greater.
The most
common is palmitaldehyde (hexadecanal) with a 16 carbon chain. Normal monoenoic aldehydes
are analogous to the monoenoic fatty acids.
It must be noticed that an aldehyde function may be found at a terminal (w)
position while an acid function is present at the other end of the carbon chain
(oxo fatty acids). These compounds have
important signaling properties in plants.
Long-chain aldehydes have been described in the waxes which impregnate the
matrix covering all organs of plants (Vermeer CP et al., Phytochemistry 2003,
62, 433). These compounds forming about 7% of the leaf cuticular waxes of Ricinus
communis were identified as homologous unbranched aldehydes ranging from C22
to C28 with a hydroxyl group at the carbon 3. Long-chain 5-hydroxyaldehydes
with chain lengths from C24 to C36, the C28 chain being the most abundant, were
identified in the cuticular wax of Taxus baccata needles (Wen M et
al., Phytochemistry 2007, 68, 2563). Long-chain aliphatic aldehydes
with chain-length from C22 to C30 are also present in virgin olive oils,
hexacosanal (C26) being the most abundant aldehyde (Perez-Camino MC et al.,
Food Chem 2012, 132, 1451).
Aldehydes may be produced during decomposition of fatty acid hydroperoxides
following a peroxidation attack. Several aldehydes
(hexanal, heptanal..) belong to aroma compounds which are found in environmental or food
systems (see the website: Flavornet). Aldehydes
(mono- or di-unsaturated) with 5 to 9 carbon atoms are produced by mosses (Bryophyta)
after mechanical wounding (Croisier E et al., Phytochemistry 2010, 71, 574).
It was shown that they were produced by oxidative fragmentation of
polyunsaturated fatty acids (C18, C20). Trans-2-nonenal is an unsaturated
aldehyde with an unpleasant odor generated during the peroxidation of
polyunsaturated fatty acids. It participates to body odor and is found mainly
covalently bound to protein in vivo (Ishino
K et al., J Biol Chem 2010, 285, 15302).
Fatty aldehydes may be determined easily by TLC or gas liquid chromatography (follow
that link). The most common method for the determination of aldehydes involves
derivatization with an acidic solution of 2,4-dinitrophenylhydrazine to form
corresponding hydrazones followed by HPLC separation and UV–VIS detection. An
optimized derivatization procedure for the determination of aliphatic C1-C10
aldehydes has been described (Stafiej A et al., J Biochem Biophys Meth 2006,
69, 15).
Other short-chain aldehydes (octadienal, octatrienal, heptadienal) are produced
via a lipoxygenase-mediated pathway from polyunsaturated fatty acids esterifying
glycolipids in marine diatoms (D'Ippolito
G et al., Biochim Biophys Acta 2004, 1686, 100). Heighteen species of
diatoms have been shown to release unsaturated aldehydes (C7:2, C8:2, C8:3,
C10:2, and C10:3) upon cell disruption (Wichard T et al., J Chem Ecol 2005,
31, 949).
Several short-chain aldehydes were
shown to induce deleterious effects on zooplankton crustaceans and thus limiting
the water secondary production (birth-control aldehydes) (D'Ippolito G et al.,
Tetrahedron Lett 2002, 43, 6133). In laboratory experiments, three
decatrienal isomers produced by various diatoms were shown to arrest embryonic
development in copepod and sea urchins and have antiproliferative and apoptotic
effects on carcinoma cells (Miralto A et al., Nature 1999, 402, 173).
Later, the copepod recruitment in blooms of planktonic diatom was shown to be
suppressed by ingestion of dinoflagellate aldehydes (Nature 2004, 429, 403).
It was demonstrated that diatoms can accurately sense a potent 2E,4E/Z-decadienal
and employ it as a signaling molecule to control diatom population sizes (Vardi
A et al., PLoS Biol 2006, 4, e60). This aldehyde triggered a
dose-dependent calcium transient that has derived from intracellular store.
Subsequently, calcium increase led to nitric oxide (NO) generation by a
calcium-dependent NO synthase-like activity, resulting in cell death in diatoms.
Myeloperoxidase-derived chlorinated aldehydes with
plasmalogens has been reported. Thus, the vinyl-ether bond of plasmalogens is
susceptible to attack by HOCl to yield a lysophospholipid and an
2-Chloro-hexadecanal
Both these chloro-fatty aldehydes have been detected in neutrophils activated
with PMA (Thukkani
AK et al., J Biol Chem 2002, 277, 3842) and in human atherosclerotic
lesions (Thukkani
AK et al., Circulation 2003, 108, 3128). Furthermore,
2-chlorohexadecanal was shown to induce COX-2 expression in human coronary
artery endothelial cells (Messner
MC et al., Lipids 2008, 43, 581). These data suggest that
2-chlorohexadecanal and possibly its metabolite 2-chlorohexadecanoic acid, both produced during leukocyte activation, may alter vascular endothelial cell
function by upregulation of COX-2 expression.
Long after the demonstration of the presence of iodinated lipids in thyroid (besides
iodinated aminoacids), it was shown that the major iodinated lipid formed in thyroid when
incubated in vitro with iodide was 2-iodohexadecanal (Pereira A et al, J Biol Chem
1990, 265, 17018). In rat and dog thyroid, 2-iodooctadecanal was determined to be
more abundant that the 16-carbon aldehyde. These compounds, which are thought to play a
role in the regulation of thyroid function, were recently shown to be formed by the attack
of reactive iodine on the vinyl ether group of PE plasmalogen.
This attack generates an unstable iodinated derivative which breaks into
lysophosphatidylethanolamine and 2-iodo aldehydes (Panneels V et al, J Biol Chem 1996,
271, 23006).
In some bacteria, aldehyde analogs of cyclopropane fatty acids were described.
Several fatty aldehydes are known to have pheromone functions. Studies in
African and Asian countries have shown that the use of 10,12-hexadecadienal
could be effective for control of the spiny bollworm Earias insulana, a
cotton pest. The sex pheromone of the navel orange worm, Amyelois transitella,
11,13-hexadecadienal, is usually used in the control of this citric pest.
A branched saturated aldehyde (3,5,9-trimethyldodecenal, stylopsal) has been
identified as a female-produced sex pheromone in Stylops (Strepsiptera),
an entomophagous endoparasitic insect (Cvacka J et al., J Chem Ecol 2012, 38,
1483).
Stylopsal
Several isoprenoid aldehydes are important in insect biology as pheromones
and in botany as volatile odorous substances. Some examples are given below:
These three terpenic aldehydes are produced in large amounts by
the mandibular glands of ants and may function as defensive repellents (Regnier
FE et al., J Insect Physiol 1968, 14, 955). In contrast, the same molecules
have a role of recruiting pheromones in honeybees
Citral, a mixture of the tautomers geranial (trans-citral)
and neral (cis-citral)
is a major component (more than 60%) of the lemongrass (Cymbopogon flexuosus)
oil. Lemongrass is widely used, particularly in Southeast Asia and Brazil, as a
food flavoring, as a perfume, and for its medicinal properties (analgesic
and anti-inflammatory). It was found that citral is a major suppressor of
COX-2 expression and an activator of PPARa
and
g
(Katsukawa
M et al., Biochim Biophys Acta 2010, 1801, 1214).
It was demonstrated that damaged leaves released 2-hexenal,
among other C6-volatile aldehydes, produced from the catalytic activity of
hydroperoxide lyase (Turlings TC et al., Proc Ntl Acad Sci USA 1995, 92, 4169).
These compounds, considered as signal molecules, can trigger several responses
in neighboring plants and may also act as antimicrobial agents (Farmer EE,
Nature 2001, 411, 854).
One important constituent of this group of aldehydes is retinal, one active form of vitamin A involved in the light reception of animal eyes but also in bacteria as a component of the proton pump.
.
Retinal exist in two forms, a cis and a trans isomer. On illumination with
white light, the visual pigment, rhodopsin is converted to a mixture of a protein (opsin)
and trans-retinal. This isomer must be transformed into the cis form by retinal isomerase
before it combines again with opsin (dark phase). Both isomers can be reduced to retinol (vitamin A) by a NADH dependent alcohol dehydrogenase.
Retinol is stocked in retina mainly in an acylated form.
Cinnamic aldehyde (cinnamaldehyde) is the key flavor compound in cinnamon
essential oil extracted from Cinnamomum zeylanicum and Cinnamomum
cassia bark. Investigations have revealed than that benzyl aldehyde
activates the Nrf2-dependent antioxidant response in human epithelial colon
cells (Wondrak
GT et al., Molecules 2010, 15, 3338). Cinnamic aldehyde may therefore
represent a precious chemopreventive dietary factor targeting colorectal
carcinogenesis.
Cinnamic aldehyde
