Page 43 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Encyclopedia of Physical Science and Technology EN001F-21 May 7, 2001 13:44

482 Alkaloids

be separated into components by physical methods. The Only a small amount of a substance is required for spec-
elemental composition of an alkaloid is determined by troscopic analysis, particularly UV spectroscopy, mass
−9
−5
combustion analyses or by high-resolution mass spec- spectroscopy, and X-ray diffraction (approx 10 ,10 ,
trometry. Structure elucidation begins in earnest with the and 10 −3 g, respectively).
spectral investigation of the substance. Ultraviolet (UV) Chemical methods are also applied to the determina-
spectroscopy (light absorption in the UV region) yields tion of structure. The major structural difference between
information on the presence of chromophoric units such alkaloids and most of the other natural products such as
as aromatic and other unsaturated systems. Infrared spec- flavonoids and terpenoids is the presence of at least one
troscopy identifies functional groups such as ketones, es- nitrogen atom. Since 1820, chemically related structure
ters, amides, and hydroxyl groups and the degree of sub- elucidation of alkaloids has been based on specific reac-
stitution of double bonds. Nuclear magnetic resonance tions occurring due to the special reactivity of the nitrogen
13
1
(NMR) spectroscopy (especially of H and C nuclei) re- atom. The original reactions are of no value today; these
veals information on the number and the electronic and include destructive distillation, potash melt, and zinc dust
stereochemical environment of the hydrogen and carbon distillation. In many cases the destructive operations led to
atoms.Massspectrometryprovidestheaccuratemolecular heterocyclic systems that were part of the alkaloids. Some
weight and the molecular formula through accurate mass of these heterocyclic systems were hitherto unknown, and
measurement of the molecular ion and may provide struc- the names given to them reflect the name of the parent
tural information for the molecule by comparison of the alkaloid. Some examples illustrate this point.
fragmentation pattern with those of analogous systems. The nomenclature of such compounds as quinoline,
In some cases it is possible to deduce the structure of isoquinoline, and quinolizidine is derived from the first
an alkaloid using only one of these techniques, especially preparation of quinoline from quinine-type alkaloids
NMR and mass spectroscopy, but usually a combination of (Scheme I)hhh. The name piperidine reflects its first prepa-
all methods is necessary. Chiroptical measurements (opti- ration from piperine, a pepper alkaloid (Piper nigrum).
cal rotatory dispersion and circular dichroism) assist in de- The zinc dust distillation of the atropine-degradation prod-
termining the optical activity of the alkaloid. This reveals, uct tropane furnished 2-ethylpyridine. Destructive reac-
by comparison with known compounds, the molecule in tions of this type are only of historical interest, since a
its three-dimensional orientation and may lead to the ab- number of alkaloid degradations led to heterocyclic sys-
solute configuration. tems that exhibited no structural relation to the alkaloid
Finally, and independently of knowledge about elemen- itself.
tal composition and spectral data, it is possible to deter- The most important reactions used in alkaloid chem-
mine the structure of a crystalline compound by X-ray istry are those that yield information about the neighbor-
diffraction analysis. An example of the results of such an hood of the nitrogen atom(s). One of the most extensively
analysis is the strychnine stereoprojection below. There is used reactions is the Hofmann degradation of exhaustive
a possibility that the absolute configuration can be deter- methylation. Treatment of an alkaloid containing a ba-
mined in this way. sic nitrogen atom with methyl iodide leads to a quaternary
ammonium salt. With base, the salt undergoes elimination
H N
of a β-proton and scission of the N—Cα bond to yield an
H olefin and a compound containing a tertiary nitrogen atom.
N H Through repetition, until the nitrogen atom is extruded as
H N(CH 3 ) 3 , this reaction permits the determination of the
O O number of bonds between the nitrogen atom and the car-
H
( )-Strychnine (absolute configuration) bon skeleton of an alkaloid. In Table III the basic stages of
the Hofmann degradation of three different alkaloid types
are given. Other specificC—N degradation reactions are
also occasionally used in structure elucidation of the alka-
loids. Depending on the variation of alkaloid structures,
oxidative, hydrolytic, reductive, and other reactions can
also be applied.

VII. CLASSIFICATION

Stereoprojection of a ( )-strychnine skeleton In the following survey of alkaloids, we consider, first, the
without hydrogen atoms (absolute configuration) nitrogen atom and its direct environment, and accordingly