Pharmacognosy, Phytochemistry, Medicinal Plants , livre ebook

A. 1/ 17/06/08 12:18 Page 2A. 1/ 17/06/08 12:18 Page 1
Part 1
COMPOUNDS OF
PRIMARY METABOLISMA. 1/ 17/06/08 12:18 Page 2A. 1/ 17/06/08 12:18 Page 3
CARBOHYDRATES
Introduction
Carbohydrates are universal constituents of living organisms. They are, at first
approximation, organic compounds with carbonyl (aldehyde or ketone) and multiple
hydroxyl functions. The carbohydrate group also encompasses oxidized or reduced
derivatives (uronic acids, polyalcohols), their esters and ethers, and their amine
derivatives (amino sugars).
In plants, they are found:
- as support elements; participating in the structure of the organism (cellulose
and other parietal polysaccharides);
- as energy reserves; in the form of polymers (for example starch) which store
solar energy captured by the photosynthetic process;
- as constituents of various metabolites; nucleic acids and coenzymes, but also
multiple glycosides, the role of which is only rarely known;
-as required precursors for all other metabolites; first formed during
photosynthesis from carbon dioxide and water, they are the basis of all organic
compounds of the living world (see Table on page 4).
Classically, they are distinguished as:
• monosaccharides, of the general formula C (H O) , characterized by then 2 n
presence of an aldehyde (aldoses) or ketone (ketoses) carbonyl function and (n-1)
hydroxyl functions *. The number of carbon atoms is most often five or six
(pentose, hexose), and ranges from three to nine;
* This is a practical, but inaccurate, generalization: 2-deoxy and 6-deoxy-sugars only have
n-2 alcohol functions; 2,6-dideoxy-sugars are also known (for example in foxgloves).A. 1/ 17/06/08 12:18 Page 4
CARBOHYDRATES4
CO hν H O2 2
mono-, oligo-,
polyosidesphotosynthesis
erythrose-4 glucose
phosphate
GLYCOSIDES
phenols, quinones,
polyacetylenes, phospho-enol
macrolides,pyruvate
fatty acids, lipids...
shikimate
flavonoids,
anthocyanins,
tannins, ...
POLYACETATES
pyruvate
SHIKIMATES
acetyl-CoA mevalonate
cycle
de Krebs
TERPENES
cinnamates, AND
lignans, STEROIDSamino acids
coumarins...
quinones
essential oils,
sesqui- and diterpenes,ALKALOIDS
saponins, cardenolides,proteins...
carotenes ...A. 1/ 17/06/08 12:18 Page 5
INTRODUCTION 5
• oligomeric and polymeric saccharides, resulting from the combination,
through a glycosidic bond, of several monosaccharide molecules (simple or true
saccharides), or of monosaccharides with non-saccharide compounds (conjugate
saccharides or glycosides):
• simple or true saccharides: they result from the combination of
monosaccharides. The number of consecutive units distinguishes oligosaccharides (less
than 10) and polysaccharides (more than 10);
• glycosides or conjugate saccharides: they result from the establishment of a
bond between a sugar (monosaccharide or oligosaccharide) and a non-sugar molecule
(the aglycone or genin). If the bond involves a nitrogen-containing function in the
aglycone, an N-glycoside results: such is the case of nucleosides. If this bond involves
an alcoholic or phenolic hydroxyl group of the aglycone, an O-glycoside results: such
is the case of the vast majority of glycosides that are specific to the vegetable kingdom
(saponins, flavonoids, glycoalkaloids, among others). C-glycosides, in which the
saccharide-aglycone bond is established directly between two carbon atoms, are less
common (see, for example p. 435, aloin of aloe, and p. 333, flavonoids of the passion
flower). Finally, S-glycosides, the sulfur-containing analogues of O-glycosides and
known as glucosinolates, are characteristic of certain plant families, particularly the
Brassicaceae and Capparidaceae.
Quite classically, we will not study glycosides as a group, but rather in various
chapters of this text, under the heading of their aglycones, which form the basis of
their pharmacological activity.
Monosaccharides, oligosaccharides, and drugs that contain them will only be
discussed briefly: their importance in the pharmaceutical context—at least in terms
of therapeutic applications—is indeed very limited.
In contrast, the multiplicity of pharmaceutical and industrial applications of
polysaccharides will lead us to devote to them, as well as to the drugs that contain
them, an important place, even if it is often their auxiliary function in manufacturing
or their dietary and nutritional impact or both, rather than their pharmacological
properties, that command the pharmacist’s attention.A. 1/ 17/06/08 12:18 Page 6A. 1/ 17/06/08 12:18 Page 7
Monosaccharides
1. Monosaccharides: Structure and Properties ...................................................................7
2. Principal Plant Monosaccharides .................................................................................12
3. Principal Monosaccharides Used in Pharmacy ............................................................14
A. Glucose ............................................................................................................14
B. Other Starch Industry Products ........................................................................16
C. Fructose ............................................................................................................17
4. Monosaccharide Derivatives Used in Pharmacy..........................................................17
A. D-Sorbitol.........................................................................................................17
B. D-Mannitol (19), Manna-ash............................................................................20
C. meso-Xylitol.....................................................................................................20
D. Derivatives of Polyalcohols .............................................................................21
5. Sugar Derivatives: Ascorbic Acid and Other Acids....................................................21
Rose hip ................................................................................................................23
Red sorrel..............................................................................................................24
Tamarind...............................................................................................................24
6. Cyclitols........................................................................................................................25
7. Bibliography .................................................................................................................25
11.. MMOONNOOSSAACCCCHHAARRIIDDEESS:: SSTTRRUUCCTTUURREE AANNDD PPRROOPPEERRTTIIEESS
The following will assume that the reader is familiar with the structure and
chemical properties of monosaccharides, and with the methods of study specific to
this group, as well as with their biosynthesis, catabolism, and biological functions.
The principle and practice of characterization and measurement methods for
monosaccharides and their derivatives, including chromatographic techniques (TLC,
HPLC, GC), are detailed in classical biochemistry and analytical chemistryA. 1/ 17/06/08 12:18 Page 8
CARBOHYDRATES8
textbooks, therefore they will not be covered here; moreover, several recent reviews
are available (see bibliography).
The introduction will merely be a reminder of elementary terminology and
nomenclature specific to this group.
Naming
In general the naming of monosaccharides is based on the number of carbon atoms
in the molecule: tetroses, pentoses, hexoses, heptoses..., and on the nature of their
carbonyl function (for example D-ribose and D-xylose are aldoses, D-ribulose and
D-xylulose are ketoses). The numbering of the carbon atoms begins with the aldehyde
carbon, or, for ketoses, so as to give the ketone carbon the lower possible number.
DD-- aanndd LL--SSeerriieess
Consider the simplest monosaccharide, glyceraldehyde (an aldotriose): it has one
asymmetric carbon, so there are two enantiomers, (R) and (S). D-glyceraldehyde and
CHO CHO
CHO CHO H C OH HO C H
H C OH HO CH HO CH HO C OH
CH OH CH OH HOC H H COH2 2
CH OH CH OH2 2
D-Glyceraldehyde L-Glyceraldehyde D-Xylose D-Arabinose
1
CHO CHO CH OH CHO CHO2
2
HCC OH H OH C O H C OH H C OH
3
H COH HO C H HO CH H C OH HO C H
4
HOC H H COH HOC H HO C H HO CH
5
H C OH HOC H H C OH HOC H HOC H
6
CH OH CH OH CH OH CH OH CH OH2 2 2 2 2
D-Allose D-Glucose D-Fructose D-Gulose D-Galactose
Linear representation of monosaccharides: principal D-series monosaccharides
The four other hexoses are epimers at C-2 and are not shown: D-altrose (epimer of D-allose), D-mannose (epimer
of D-glucose), D-idose (epimer of D-gulose) and D-tallose (epimer of D-galactose). The same applies to the two
other pentoses, D-ribose and D-xylose.A. 1/ 17/06/08 12:18 Page 9
MONOSACCHARIDES 9
L-glyceraldehyde are defined arbitrarily and by convention as having the secondary
hydroxyl group on the right or on the left side of the molecule, respectively, in the
Fischer projection (vertical representation, aldehyde carbon at the top).
Again by convention and by reference to glyceraldehyde, it is the orientation of
the hydroxyl group most distant from the carbonyl group that determines if a
monosaccharide belongs to the D or to the L series. Because this rule is arbitrary, the
fact that a sugar belongs to either series does not predict its optical activity. The vast
majority of natural monosaccharides belong to the D series (exceptions: L-rhamnose,
L-arabinose, and L-fucose).
Cyclic Structure of Monosaccharides
The particular chemical behavior of monosaccharides (see general biochemistry
textbooks) has led to the postulate that they exist in a cyclic form involving the
carbonyl group and one hydroxyl group. The principal consequences are as follows:
- depending on the nature of the bridge (1-4 or 1-5), the cycle is either a furan or a
pyran (furanoses and pyranoses);
- generally, aldohexoses form pyranose rings and ketohexoses form furanose rings;
- cyclization