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 (CHNO) - is the principal body formed, while in the case of quinine, quininic acid (CHNO) 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 CHN, that is, it is benzene with CH replaced by N. The relationship between these and piperidine is seen in the following formulae:
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 (CH), its formula being taken as CH(CH)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] = 31° 87' as compared with the [a] = 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 formulae show the constitutional relationship of these compounds:
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.