THE NON — EXISTENCE OF “PROTAGON” AS A DEFINITE CHEMICAL COMPOUND
Authors: Rosenheim Otto , Tebb M. Christine 
Published: December 2014

The question of the homogeneity of “protagon,” a chemically inert product which can be recrystallised, should not be a difficult one to settle, and it seems necessary to settle it finally and without doubt. The importance which the lipoids have recently acquired in connection with biological problems in general, demands a definite chemical knowledge of these substances. The uncertainty of the chemical nature of “protagon” especially has already given rise to misunderstandings and wrong interpretations. Instead of wasting further time in the endeavour to prepare in a pure state a complicated product like “protagon,” it seems to us more profitable to study, from a chemical point of view, its constituents and their cleavage products. We began by isolating the main phosphatide (sphingomyelin) contained in “protagon,” but before proceeding with its study it seemed essential to settle the chemical entity of the product which serves for its preparation. As the result of this work we have arrived at the following conclusions:—(1) The so‐called “protagon” of Liebreich (1865) and his successors is identical in chemical composition and physical properties with Couerbe's “cérébrote” (1834).(2) The elementary analyses of different “protagon” preparations show variations of such a degree as to suggest that this product does not represent a chemical entity.(3) “Protagon” contains varying amounts of adsorbed inorganic substances, especially potassium.(4) The composition of “protagon” undergoes a complete change by repeated recrystallisation from moderate or large volumes of alcohol. Nearly phosphorus‐free galactosides result finally.(5) The composition of “protagon” undergoes a complete change by recrystallisation from pyridine. This leads to the isolation of a phosphorus‐rich substance (sphingomyelin P = 4 per cent.).(6) By one single recrystallisation of “protagon” from various mixtures of solvents its chemical composition is completely changed (the P per cent. varying from 0·07 per cent. to 3·13 per cent.).(7) The amount of galactose obtainable by hydrolysis from different “protagon” fractions varies from traces to 16 per cent.(8) The optical activity, calculated as specific rotation, is [α]30D = +7° for those “protagons” in which the phosphorus percentage happens to be approximately 1 per cent., whilst that of the fractions varies from + 2·7° to +7·5°.(9) The phosphorus‐rich constituent (sphingomyelin) of “protagon” gives rise to the phenomenon of “spherorotation” which is produced by the suspension of spherocrystals.(10) “Artificial protagon,” i.e. a mechanical mixture of impure galactosides and phosphatides in the proportion as obtained from “protagon,” has the same chemical composition and optical activity as the original “protagon.”(11) The microscopical appearance of the fractions separated out from “protagon” is strikingly different, especially under the polarising microscope. Their mechanical mixture is identical in appearance under the polarising microscope with the original “protagon.”(12) “Protagon” possesses an indefinite melting‐point. The phosphorus‐poor fractions separated out from “protagon” fuse between 168° and 178° C. and the phosphorus‐rich fractions between 210° and 216° C.