In the note on the constitution of alkaloids in a recent issue, we
referred more especially to what we may term the less highly organized
bases. Most of our knowledge, as we now have it, regarding such
alkaloids as muscarine and choline has been acquired during the past
dozen years. This is not exactly the case with the higher groups of
alkaloids--the derivatives of pyridine and quinoline. It so happens
that the oldest alkaloids are in these groups. They have, almost
necessarily, been subjected to a longer period of attack, but the
extreme complexity of their molecules, and the infinite number of
differing parts or substances into which these molecules split up when
attacked, are the main cause of the small progress which has been made
in this department. All, however, yield one or more bodies or bases in
common, while each has its distinctive and peculiar decomposition
product. For example, cinchonine and quinine both afford the basic
quinoline under certain conditions, but on oxidation of cinchonine, an
acid--cinchoninic acid (C_{10}H_{7}NO_{2})--is the principal body
formed, while in the case of quinine, quininic acid (C_{10}H_{9}NO_{3})
is the principal product. The acquirement through experiment of such
knowledge as that is, however, so much gained. We find, indeed, that
obstacles are gradually being cleared away, and the actual synthetic
formation of such alkaloids as piperidine and coniine is a proof that
the chemist is on the right track in studying the decomposition
products, and building up from them, theoretically, bodies of similar
constitution. It is noteworthy that the synthesis of the alkaloids has
led to some of the most brilliant discoveries of the present day,
especially in the discovery of dye stuffs. Many of our quinine
substitutes, such as thalline, for example, are the result of
endeavors to make quinine artificially. If there is romance in
chemistry at all, it is to be found certainly in this branch of it,
which is generally considered the most uninteresting and unfathomable.
We may take piperidine and coniine as examples of the methods followed
in alkaloidal synthesis; these are pyridine bases. Pyridine has the
formula C_{5}H_{5}N, that is, it is benzene with CH replaced by N. The
relationship between these and piperidine is seen in the following
formulæ:
CH N NH
/ \ / \ / \
HC CH HC CH H_{2}C CH_{2}
| | | | | |
HC CH HC CH H_{2}C CH_{2}
\ / \ / \ /
CH CH CH_{2}
(Benzene,) (Pyridine,) (Piperidine,)
(C_{6}H_{6}) (C_{5}H_{5}N) (C_{5}H_{11}N)
If we introduce six hydrogen atoms into pyridine, we convert it into
piperidine. Ladenburg succeeded in so hydrogenizing pyridine by acting
upon an alcoholic solution with sodium, and from the base which was
formed he obtained a platinochloride which agreed with the similar
double salt of piperidine. He has also prepared it from trimethyline
cyanide by the action of sodium. Pentamethylinediamine is the
principal intermediary product, and this gives piperidine when
distilled with superheated steam. He has proved that the alkaloid so
obtained is identical with that prepared from piperine. Another
curious point which Ladenburg has lately proved is that cadaverine
(one of the products of flesh decomposition) is identical with
pentamethylinediamine, and that its imine is the same as piperidine.
The synthesis of coniine by Ladenburg is one of the most notable
achievements of modern chemistry. He at first supposed that this
alkaloid was piperidine in which two hydrogen atoms were replaced by
the isopropyl radical (C_{3}H_{7}), its formula being taken as
C_{5}H_{9}(C_{3}H_{7})NH. But he has since changed his view, as will
be seen from what follows. In its synthesis 1,000 grammes of picoline
were first converted into alphapicoline, 380 grammes being obtained.
This was heated with paraldehyde, whereby it was converted into
allylpyridine (48 grammes), and this by reduction with sodium yielded
alpha-propylpyridine, a body in almost every respect identical with
coniine. The more important difference was its optical inactivity, but
he succeeded in splitting up a solution of the acid tartrate of the
base by means of _Penicillium glaucum_. Crystals separated which had a
dextro-rotatory power of [_a_]_{D} = 31° 87' as compared with the
[_a_]_{D} = 13° 79' of natural coniine. This brief account conveys but
a faint idea of the difficulties which were encountered in these
researches. Optical methods of examination have proved of great value,
and are destined to play an important part in such work.
Among the most complex alkaloids are those of the quinine group. As
yet chemists have got no further with these than the oxidation
products; but the study has afforded us several new antipyretics and
many interesting facts. It has been found, for example, that
artificial quinine-like bodies, which fluoresce and give the green
color with chlorine water and ammonia, have antipyretic properties
like quinine, but their secondary effects are so pernicious as to
prevent their use. If, however, such bodies are hydrogenized or
methylated they lose their fluorescing property, do not give the green
color, and their secondary effects are removed. Knowledge of these
facts led to the discovery of thalline. It is prepared from
paraquinanisol, one of the objectionable bodies, by reduction with tin
and hydrochloric acid. The following formulæ show the constitutional
relationship of these compounds:
CH CH CH CH_{2}
/ \ / \ / \ / \
(CH_{3}O)C C CH (CH_{3}O)C C CH_{2}
| | | | | |
HC C CH HC C CH_{2}
\ / \ / \ / \ /
CH N CH NH
Paraquinanisol Thalline
C_{9}H_{6}.CH_{3}.NO. C_{9}H_{10}.CH_{3}.NO.
It is evident from the difficulties which have been encountered in
this department of chemistry, and more especially from the costly
nature of the work, that it will be many years before it will
influence the manufacture of alkaloids from the drugs which yield
them. Ladenburg has synthetized coniine, but he has not yet ventured
to assert that his product will replace the natural alkaloid.--_Chem.
and Druggist._
* * * * *
The _Southern California Advocate_ reports another magnificent
donation of lands to the University of Southern California by Mr. D.
Freeman, the owner of the Centinella ranch near Los Angeles--six
hundred thousand dollars in all given to found a school of applied
sciences, $100,000 for building and apparatus and $500,000 for
endowment. The buildings will be in the vicinity of Inglewood, the new
and beautiful town on the Ballona branch of the California Central.
* * * * *