Natural products

A Natural product is a chemical substance or

compound produced by a living organism that
found in nature in broadest sense, natural
products include any substance produced by
life.
 ALKALOID
S

New Definition:- Alkaloids are cyclic organic

compounds containing nitrogen in a negative state of
oxidation with limited distribution among living
organisms.
Alkaloids of Opium Poppy (Papaver)
Morphine named for Morpheus, the god of dreams in the
Greek mythology
Friedrich Serturner isolated Morphine at 1806 and this
gave rise to the study of alkaloids
In 1819, Carl Meissner (Halle) gave the name alkaloids
after the plant al-qalifrom which soda was isolated
(sodiumcarbonate called alkaliin arabic)
Alkaloids first defined as pharmacologically active
nitrogen containing basic compounds of plant origin
(nowadays expanded)
 The 18th century
At the end of the 18th century, crude drugs were still being used as powders,
simple extracts, or tinctures.
The era of pure compounds (In 1803, a new era in the history of medicine)
Isolation of morphine from opium
Strychnine (1817)
Quinine and caffeine (1820)
Nicotine (1828) Nicotine Strychnine morphine

Atropine (1833) caffeine

Cocaine (1855)

Quinine
Atropine Cocaine
4
 Alkaloid Natural Products

oquinoline alkaloids
n isolert fra opium 1803 (Morpheus: gresk svngud)

HO O OH

Derivativeofphenantrene

nalogs, binds to opiopeptide (endorfin / enkefalin) reseptors

S
O
HO
N N
N H
O
OH NH
H O
O H
N N
O
H2 N O
O
HO OH
OH Metenkefalin
Morfin TyrNterminal
KJM5230-H04
OH hosopiopeptider
3000 Year History of Alkaloids use by
Humans
In most human history, alkaloids from plant extracts
have been used as ingredients in potions (liquid medicine)
and poisons.
Ancient people used plant extracts containing alkaloids
for treating a large number of ailments including:
snakebite, fever and insanity.
In the middle east-the latex of Opium Poppy (Papaver)
was already used at 1200 B.C.
Distribution and occurrence:

Rare in lower plants.

Dicots are more rich in alkaloids than Monocots.

Families rich in Alkaloids: Apocynaceae, Rubiaceae,

Solanaceae and Papaveracea.

Families free from Alkaloids: Rosaceae, Labiatae

Distribution in Plant:

All Parts e.g. Datura.

Barks e.g. Cinchona
Seeds e.g. Nux vomica
Roots e.g. Aconite
Fruits e.g. Black pepper
Leaves e.g. Tobacco
Latex e.g. Opium
Forms of
Alkaloids:
Free bases
Salts with Organic acids e.g.
Oxalic, acetic acids
Salts with inorganic acids e.g. HCl,
H2SO4.
Salts with special acids e.g. Meconic
acid in Opium Quinic acid in
Cinchona
Glycosidal form e.g. Solanine in
Solanum.
 Function in
They
Plants
may act as protective against
insects and herbivores due to their
bitterness and toxicity.
They are, in certain cases, the final
products of detoxification (waste
products).
Source of nitrogen in case of nitrogen
deficiency.
They, sometimes, act as growth
regulators in certain metabolic systems.
They may be utilized as a source of
energy in case of deficiency in carbon
dioxide assimilation.
 Nomenclature:
Trivial names should end by "ine". These
names may refer to:
The genus of the plant, such as Atropine
from Atropa belladona.
The plant species, such as Cocaine from
Erythroxylon coca.
The common name of the drug, such as
Ergotamine from ergot.
The name of the discoverer, such as
Pelletierine that was discovered by Pelletier.
The physiological action, such as Emetine
that acts as emetic, Morphine acts as
narcotic.
A prominent physical character, such as
Hygrine that is hygroscopic.
 Prefixes and
suffixes:
Prefixes:
"Nor-" designates N-demethylation or N-demethoxylation, e.g.
norpseudoephedrine and nornicotine.
"Apo-" designates dehydration e.g. apomorphine.
"Iso-, pseudo-, neo-, and epi-" indicate different types of
isomers.
Suffixes:
"-dine" designates isomerism as quinidine and cinchonidine.
"-ine" indicates, in case of ergot alkaloids, a lower
pharmacological activity e.g. ergotaminine is less potent than
ergotamine.
 Physical
I- Condition:Properties:
Most alkaloids are crystalline solids.
Few alkaloids are amorphous solids e.g.
emetine.
Some are liquids that are either:
Volatile e.g. nicotine and
coniine, or
Non-volatile e.g. pilocarpine
and hyoscine.
II- Color:
The majority of alkaloids are colorless but
some are colored e.g.:
Colchicine and berberine are yellow.
III- Solubility:
Both alkaloidal bases and their salts are soluble in alcohol.
Generally, the bases are soluble in organic solvents and insoluble
in water
Exceptions:
Bases soluble in water: caffeine, ephedrine, codeine, colchicine,
pilocarpine and quaternary ammonium bases.
Bases insoluble or sparingly soluble in certain organic solvents:
morphine in ether, theobromine and theophylline in benzene.

Salts are usually soluble in water and, insoluble or sparingly

soluble in organic solvents.
Exceptions:
Salts insoluble in water: quinine monosulphate.
Salts soluble in organic solvents: lobeline and apoatropine
hydrochlorides are soluble in chloroform.
 IV-
Isomerization:
Optically active isomers may show different
physiological activities.
l-ephedrine is 3.5 times more active than d-
ephedrine.
l-ergotamine is 3-4 times more active than d-
ergotamine.
d- Tubocurarine is more active than the
corresponding l- form.
Quinine (l-form) is antimalarial and its d-
isomer quinidine is antiarrythmic.
The racemic (optically inactive) dl-atropine is
physiologically active.
Taste of alkaloids:-

They are generally bitter in taste and are optically active

and laevorotatory.

Most of the alkaloids contain oxygen.

Most of the alkaloids contain one or two nitrogen atoms

usually in the tertiary state in a ring system. Most of alkaloids
react with methyl iodide to form crystalline adduct.
 Chemical
I- Nitrogen:Properties:
Primary amines R-NH2 e.g.
Norephedrine
Secondary amines R2-NH e.g.
Ephedrine
Tertiary amines R3-N e.g.
Atropine
Quaternary ammonium salts R4-N e.g d-
Tubocurarine

II- Basicity:
R2-NH > R-NH2 > R3-N
 Classification of alkaloids

A.Taxonomical:- The classification is based on the

plant family. Thus, alkaloids may be described as
Solanaceous or Papilionaceous without refrence to
the chemical type of alkaloid present. EX:-
Solanaceaetropane, steroidal; papilionaceae
quinolizidine and pyrrolizidine.

B. Pharmacological:- This classification of alkaloids

according to their use or physiological activity. Ex-
analgesic alkaloids, cardioactive alkaloids
C. Biosynthetic:- This method of classification is based on the
type of precursors or building block compounds used by plant
to synthesize complex structure. Hundreds of Indole alkaloids
are known all are derived from the amino acid tryptophan and
mevalonic acid, as are the Ergot and Cinchona alkaloids.
Similarly , morphine, papaverine, narcotine are phenylalanine
tyrosine derived molecules.

D. Chemical:- The chemical classification is universally adopted

and depends on the fundamental ring structure present in the
alkaloids. Thus quinine is regarded as a quinoline type ,
papaverine and isoquinoline. Morphine which is regarded as a
phenanthrene derivative is included in quinolines.

On the basis of chemical classification

1. Phenylethylamine alkaloids
2. Pyrroline alkaloids
3. Pyridine or piperidine alkaloids
4. Pyridine-pyrrolidine alkaloids
5. Tropane alkaloids
6. Quinoline alkaloids
7. Isoquinoline alkaloids
8. Phenantherene alkaloids
9. Indole alkaloids
10.Tropolone alkaloids
Another Classification:

True (Typical) alkaloids that are derived from amino

acids and have nitrogen in a heterocyclic ring.
e.g : Atropine

Protoalkaloids that are derived from amino acids and do

not have nitrogen in a heterocyclic ring.
e.g : Ephedrine

Pseudo alkaloids that are not derived from amino acids

but have nitrogen in a heterocyclic ring.
e.g : Caffeine

False alkaloids are non alkaloids give false positive

reaction with alkaloidal reagents.
 Isolation of Alkaloids
Isolation and purification of an alkaloids from a plant is always not
a simple process because an alkaloid bearing plant generally
contains a complex mixture of several alkaloids.

a) First to detect the presence of alkaloids in the plant

The detection of alkaloids in the plants are carried out by using
several reagent those reagents are called alkaloid reagents.
Ex:-Mayers reagent (potassium mercuric iodide)
Drogendorffs reagent (potassium bismuth iodide)
Wagners reagent (iodine dissolved in KI)
Hagers reagent (saturated solutions of picric acid in water)
some of the precipitating agents like Chloroplatinic
(H2PtCl6) and Chloroauric (HAuCl4) are used to detection of
alkaloids in very small amount by precipitation and these
precipitate are having characteristic colour etc
b) The separation of relatively small percentage (dry
weight basis) of alkaloids from large amount of
extraneous plant material. Ex:- opium contains 10%
morphine, Cinhona 5-8% quinine, Atropa belladonna
0.2% hysocyamine and Rauwolfia serpentina root 0.1 to
0.2% reserpine.

c) Separation and purification of individual alkaloids from

the crude extract.
There are three general methods are used for isolation of
alkaloids. The alkaloids are shows properties of simple
salts and many alkaloids are water soluble but much less
soluble in organic solvents, where as reversible is true
for free bases.
Extraction, Purification and Isolation of Alkaloids from
Powdered plants

Extraction and purification

Method I:
The powder is treated with alkalis to liberates the free
bases that can then be extracted with water
immiscible organic solvents.

Method II:
The powdered material is extracted with water or
aqueous alcohol containing dilute acid. Alkaloids
are extracted as their salts together with
accompanying soluble impurities.

Method III:
The powder is extracted with water soluble organic
solvents such as MeOH or EtOH which are good
solvents for both salts and free bases.
 Plant material and solvent

Organic solvent dissove Alkaloids

Organic solvent dissove Impurities
Extract

Concentration Acidification
Alkalinization

Acidified Extract (Alk. as salts)

Alkaline aqueous layer
 Disadvantages of method

Mixing of the powdered material with alkali is tedious and

requires special equipment.

Deep penetration of the moist drug with solvent is unlikely;

therefore a large number of extractions are required.

Ether is a fire hazard and also much of it is lost by retention

in the exhausted drug, which makes the process costly.

Chlorinative solvents are a health hazard.

Method 2, the powdered drug is extracted with methonal,
ethenol or isopropanol and resultant extract submitted to the
same process as that of the method -1.

Method -2, however requires no alkali gives good

penetration of the drug, therefore only four extraction may
be needed.

Method -3. the alkaloid is extracted from the plant material

with acidulated water or alcohol. Pigments and other
unwanted materials are removed from initial extract by
shaking with suitable solvent. The free alkaloids are then
precipitated from the aqueous fraction by addition of excess
alkali.
This method is very cheap and large scale extraction based.
General methods for Determining Structures of alkaloids

Molecular formula Determination:- After a pure compounds

has been obtained to identified the elemental composition and
hence empirical formula by combustion method. The molecular
weight is determined by Rast prociger (depression of the freezing
point) to estimate the molecular formula.

By calculating the number of double bonds equivalent's

corresponding to the found molecular formula which will gives
idea about double bond or cyclization of the chain decreases the
molecular formula by two hydrogen atom correspond to saturated
aliphatic compounds.
EX:- Hexene (C6 H12 ) Hexane (C6H14) ,
Benzene (C6 H6 ) Hexane (C6H14) the eight hydrogen deference
corresponding to 8/2 or 4 double bond equivalents.
The above procedure is valid for simpler compounds only
.However , for complex formulae, where elements other than
hydrogen and carbon are present, the simpler method is that for
any formula CaHbNcOd the number of double bond equivalents
is given by the following expression:

a-(1/2)b+(1/2)c+1
EX:- C8H15NO,
8-15/2+1/2+1=2

Functional group analysis:-

Application of classical techniques of organic analysis and
IR examination can reveal the nature of the functional groups
present.
 Functional nature of oxygen:-
If an alkaloid contains oxygen, it may be present as phenolic or
alcoholic, methoxy, acetoxyl, benzoxyl, carboxylic, carbonyl
etc.
A. Hydroxyl group:- hydroxyl group react to form acetate on
treating with acetic anhydride or acetyl chloride.

However, the above test for oxygen should be applied

carefully because primary amines if present in an alkaloid also
yield acetyl and benzoyl derivatives.
 Then the number of hydroxyl groups is determined by
acetylationor Zerewitnoffsmethod. In the former method, the
number of hydroxyl groups is determined by acetylating the
alkaloid and hydrolysingthe acetyl derivative with a known
volume of IN NaOH.

The excess of alkali is estimated by titrationwith a standard

solution of HCl. The number of acetyl groups or hydroxyl
groups can be calculated from the volume of alkali used for
hydolysis.
b) Carboxylic group:

The solubility of an alkaloid in aqueous sodium carbonate or

ammonia reveals the presence of carboxylic group. The
formation of ester on treatment with an alcohol also reveals the
presence of carboxylic group.

The number of carboxylic groups may be determined by

volumetrically by titration against a standard barium hydroxide
solution using phenolphthalein as an indicator or
gravimetrically by silver salt method.
c) Oxo group:
The presence of this group is ascertained by the reaction of
an alkaloid with hydroxylamine, semicarbazide or
phenylhydrazinewhen the corresponding oxime, semicarbazone or
phenylhydrazone are formed.

Distinction between an aldehyde and a ketone can be made

on the basis of reduction and oxidation reactions.
d) Methoxy group:
The detection of this group and its number may be determined
by the Zeisel determination, analogous to the Herzeg
Meyermethod for Nmethyl groups.
In this method, a known weight of alkaloid is heated with
hydriodic acid at its boiling point (126C) when the methoxyl
groups are thereby converted into methyl iodidewhich is then
absorbed by ethanolic silver nitrate and the precipitated silver
iodide is filtered, dried and weighed. From the weight of silver
iodide, the number of methoxyl groups may be calculated.
 For example, papavarine, C20H21O4N, when treated with
hydrogen iodide, consumes 4 moles of hydrogen iodide,
producing 4 moles of silver iodide and thus confirming the
presence of four OCH3groups.

e)Ester and amide groups:

These groups can be detected and estimated by observing
The products of their alkaliod on acid hydrolysis.
4) Nature of Nitrogen:

Some alkaloids are contain nitrogen . But in the majority of

alkaloids it is present as a part of a heterocyclic system.
Therefore, it must be either a secondary (=NH) or tertiary(=N
CH3 or =N).

However, there are phenylalkyl amine type of alkaloids

(adrenaline, ephedrine, etc) which do not contain nitrogen as a
part of a heterocyclic ring but in the form of a primary amino (
NH2) group.

a)The general reactions of the alkaloid with acetic anhydride,

methyl iodide and nitrous acid often show the nature of the
nitrogen.
 If the alkaloid reacts with one mole of methyl iodide to form
an Nmethyl derivative, it means that a secondary nitrogen atom
is present. For example, coniine, C8H17N reacts with one mole of
methyl iodide to form an Nmethyl derivative, indicating that
coniine must contain secondary nitrogen atom.
 If an alkaloid reacts additively with one mole of
methyl iodide to form crystalline quaternary salt, this
indicates that nitrogen atom present in this alkaloid is
tertiary. For example, nicotine reacts additively with
two moles of methyl iodide, indicating that it contains
both nitrogen atoms as tertiary.
 One can detect the tertiary nitrogen atom in an
alkaloid by treating it with 30 % hydrogen peroxide when
tertiary nitrogen is oxidized to amine oxide.

b) The presence of N-methyl group is often detected by

distillation of alkaloid with sodalime when methyl amine
is obtained. For example, nicotine on heating with soda
lime yields methylamine indicating that it must contain a
Nmethyl group.
Herzing-Meyers method is used to detect and estimate
the number of methyl group attached to N atom. This
method is consists in cleaving N-methyl amine present
in an alkaloid with hydriodic acid at 150 -300 C and
estimate the amount of methyl iodide so formed by
conversion to silver iodide with silver nitrate solution.
 NMR spectroscopy may also be utilized for the rapid
detection of Nmethyl and Nethyl groups in alkaloids.

5) Estimation of CMethyl groups:

Cmethyl groups are quantitatively estimated by the

KuhnRoth oxidation, the acetic acid formed being
distilled off and distillate titrated against standard base.
6) Degradation Of Alkaloids:

The reactions used in degradation of alkaloids are

as follows:

(a) Hofmann exhaustive methylation method

(b) Emdes degradation
(c) Reductive degradation and zinc dust distillation
(d) Alkali fusion
(e) Oxidation
(f) Dehydrogenation
a) Hofmanns Exhaustive Methylation Method:
The principle of this method is that compounds,
which contain the structural unit =CH=CN+R3OH,-
eliminate a trialkylamine on pyrolysis at 200C or above
to yield an olefin.
 If the nitrogen atoms forms a part of a cyclic structure,
two or three such cycles are essential to liberate the
nitrogen and expose the carbon skeleton.

However , this method is applicable only to reduced

ring systems such as piperidine and actually fails with
analogous unsaturated compounded such as pyridine and
therefore the latter should be first of all converted into the
former
 When a molecule of water is eliminated from
quaternary ammonium hydroxide, hydrogen atom is
always eliminated from the position, if this hydrogen
is not available, the reaction fails
 The hofmannsdegradation method can be applied
to hordenine methyl ether which yields pmethoxy
styrene.
b) Emdes degradation:
If the alkaloid does notcontain a hydrogen atom, the
Hofmanns exhaustive methylation method fails. In such
cases, Emdes method may be employed.

In this method, the final step involves reductive

cleavage of quaternary ammonium salts either with
sodium amalgam or sodium in liquid ammonia or by
catalytic hydrogenation:
 Emdes method can be demonstrated by considering
the case of isoquinoline:

NM
e
c) Reductive Degradation and Zinc Dust
Distillation:
In some cases the ring may be opened by heating
with hydiodic acid at 300C, e.g.,

HI

300C
 Zinc dust distillation produces simple fragments from
which one can draw the conclusion about the carbon
framework of the alkaloid molecule.

Zinc dust also brings about dehydrogenation or

removal of nitrogen if present. For example,

As conyrineis formed by loss of six hydrogen atoms, it

means that coniine must contain a piperidine ring
d) Alkali fusion:
This is very drastic method which is often employed to
break down the complex alkaloid molecule into simpler
fragments, the nature of which will give information on the
type of nuclei present in the alkaloid molecule. For
example, adrenaline when fused with solid potassium
hydroxide yields protocateochuic acid, indicating that
adrenaline is a catechol derivative.
e) Oxidation:
This method gives useful information about the
structure of alkaloid. By varying the strength of the
oxidising agents, it is possible to obtain a variety of
oxidation products. For example,

(i)In order to carry out mild oxidation, hydrogen peroxide,

iodine in ethanolic solution, or alkaline potassium
ferricyanide are usually used.
(ii) In order to carry out moderate oxidation, acid or
alkaline potassium permanganate or chromium trioxide in
acetic acid are generally used.
(iii) For carrying out vigorous oxidation, potassium
dichromatesulphuric acid, chromium trioxidesulphuric
acid, concentrated nitric acid or manganese dioxide
sulphuric acid are used. These reagents usually break up
an alkaloid into smaller fragments whose structures are
either already known or can be readily ascertained. For
example,
 From this reaction, it can be concluded that nicotine
contains a pyridine ring having a side chain in position.

This classification of oxidizing agents is not rigid

because the strength of an oxidizing agent depends to
some extent on the nature of the alkaloid which is being
oxidized.

(f) Dehydrogenation:
When an alkaloid is distilled with a catalyst such as
sulphur, selenium or palladium, dehydrogenation takes
place to form relatively simple and easy recognizable
products which provide a clue to the gross skeleton of the
alkaloid
 During dehydrogenation, there occurs the elimination of
peripheral groups such as hydroxyl and Cmethyl.

(7) Synthesis:

The structure of the alkaloid arrived at by the exclusive

analytical evidence based on the foregoing methods is only
tentative. The final confirmation of the structure must be
done by the unambiguous synthesis.
(8) Physical Methods:
In alkaloid chemistry, the most important instrumental
methods are as follows:

(a) Ultraviolet spectroscopy

(b) Infrared spectroscopy
(c) Mass spectroscopy
(d) Optically rotatory dispersion and circular dichroism
(e) Conformational analysis, and
(f) Xray diffraction
(a) Ultraviolet Spectroscopy:

This is mainly used to establish the class and/or

structural type to which the alkaloid being investigated
belongs. Such assignments are made because ultraviolet
spectrum of a compound is not a characteristic of the
whole molecule but only of the chromophoric system(s)
present.

The usual practice is to record the ultraviolet spectra of a

very large number of different types of alkaloids. Then, the
data are analyzed and categorized with respect to structure
correlation.
 Each group of alkaloids having a particular
chromophoric system benzene, pyridine, indole, quinoline,
etc . yields characteristic absorption maxima and extinction
coefficients.

Therefore, the comparison of these data with those

observed for a new alkaloid may allow the identification of
the exact nature of the aromatic or heterocyclic system in
the new compound.
(b) Infrared spectroscopy:

In alkaloid chemistry, it is mainly used to ascertain the

presence and sometimes the absence of particular functional
group.
 The presence of aldehyde, ketone, alcohols, phenols,
ester, amide, lactone, carboxylicacid, carbonyl grroups
and primary and secondary amines can rapidly be
identified and distinguished by comparison of the
observed frequencies with those reported for structural
related compounds.

One can also ascertain the presence of Omethyl, N

methyl and aromatic groups from the infrared spectrum
of an alkaloid but the quantitative analysis of such
groups is best accomplished by NMR spectroscopy.
(c) Mass spectroscopy:
This technique is quite useful because it gives quite useful
information about the alkaloid like.

(i) The molecular weight.

(ii) The empirical formula by accurate mass measurement of the
molecular ion, and
(iii) Knowledge of the molecular structure by comparison of the
fragmentation pattern with those of analogous system.

Most of the success has been achieved in the case of

polycyclic indole alkaloids because the indole nucleus of these
substances gives rise to an abundant, stable molecular ion which
subsequently undergoes decomposition by highly specific bond
fusion involving the acyclic portion of the molecule containing
the other nitrogen atom(s).
d) Optically rotatory dispersion and circular
dichroism:
These are only instrumental methods which are mainly
used for elucidation of the stereochemistry of alkaloids but
their application is restricted to those compounds which
are optically active, i.e., to those in which a rotation
reflection symmetry axis is absent.

Due to this reason, few alkaloids of the yohimbine,

aprophine, morphine and benzlisoquinoline series have
been examined so far by these techniques.
e) Conformational Analysis:
The principles of conformational analysis have been
widely used to establish the stereochemistry as well as
physical properties and chemical reactivity of alkaloids.

The approach is mainly experimental which involves

determination, correlation and interpretation of the
kinetics and product ratios obtained from simple
chemical transformations such as reduction of double
bonds and carbonyl groups, hydrolysis and esterfication,
oxidation of alcohols and quaternization of amines,
epimerization, etc
f) Xray Diffraction:

This technique is widely used to study alkaloids

because it gives the exact structure of he molecule,
including bond angles and bond lengths; it also gives the
information about the relative stereochemistry, including
information on overcrowding twisted bonds, etc.

Xray diffraction method is also useful to reveal the

absolute configuration of the molecule.
 Reserpin
e
The molecular formula is C33H40N2O9.
On heating with HI it gives 5 moles of
methyl iodide indicate the presence of 5
methoxy group.

As reserpine is weak base, both the

nitrogen atom must be involved in ring
formation.

The reserpine reacts with acetyl

chloride it indicate the presence of NH
group. It is further confirmed by IR spectra
 Reserpine upon alkaline hydrolysis gives
methanol, 3,4,5-trimethoxybenzoic acid and
reserpic acid.

Since reserpine has on two COOH and

two OH groups suggest that reserpine is a
Diester.
Structure of reserpic acid:- By the usual
test reserpic acid is found to be two
 On permanganate oxidation reserpic
acid affords 4-methoxy-N-oxalyl antranilic
acid as one of the confirming the
presence of indole nucleus.

reserpic acid on
fusion with potash
gives 5-hydroxy
isophthalic acid.
Now since one
The acidic of of isophthalic acid must
group
be the acidic group of the reserpic acid.
The hydroxyl and carboxyl groups in
reserpic acid are meta to each other.
Biosynthesis
of Alkaloid
BIOSYNTHESIS OF ALKALOIDS :
It is well established that alkaloids are derived from
Amino acid.

the most common ones are: phenylalanine,

tyrosine, lysine, ornithine, histidine,
tryptophan and anthranilic acid.
 Biosynthesis of nicotinic acid

Pyridin
e
alkaloid