RECENT ADVANCES in the CHEMISTRY of VITAMINS* IDA B. ROUTH New York University, Washington Square East, New York City Recent work has thrown considerable light upon the chemical structure of carotene and its importance as the probable precursor of vitamin A. It has been announced that the zlitamin itself has been prepared from carotene. A crystalline preparation of oitamin B1 has been made, and its empirical formula ascertained. Vitamin C has been prepared, it i s claimed, from narcotine and i s the di-phenol of that alkaloid. A more
recent report relates the oitamin to the "hexuronic acid" studied as a n oxidation-reduction factor i n adrenal cortex, oranges, and cabbage. Vitamin D has been prepared in crystalline form by investigators in Germany, in England, and i n this country. I t i s a n intermediate irradiation product of ergosterol. Of vitamin E little i s , as yet, k n m .
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S
0 MUCH has been accomplished in the last few years, and even in the last few months, in the field of vitamin chemistry that a survey of the more recent publications in this field would seem to be of particular value just a t this point. The Egyptians, Herodotus thought, had thicker skulls than the Persians, because they exposed their heads constantly to the burning rays of the sun. The mariners of the sixteenth century knew that a supply of citrus juices warded off scurvy. But the concept of "vitamin" is a very recent thing. Practically all our definite knowledge began with the experiments of Eijkman, in 1887, who was able to induce a neuritic disease in fowls, similar to beri-beri in humans, by feeding polished rice. He established the fact that the disease was not due to the presence of pathogenic organisms. Nor was it a result of insufficient mechanical intestinal stimulation, nor lack of food value. He assumed that the excess of starch fed led to some sort of intoxication, as a result of disturbed carbohydrate metabolism, and that in the cure of the disease upon feeding the rice polishings, some factor was fed which counteracted the disturbance. This was of course erroneous, but he did point out the fact that some factor present in the polishings was necessary for normal maintenance of health. To take up in detail the history of the work in this field would require a monograph. It is the purpose of this paper to take up only those more specific facts directly related to the recent developments in the preparation of the active substance in pure form.
carrots, tomatoes, red cabbage, and other vegetables. Many investigators then noted that the active substance was usually accompanied by these colored materials, and the idea was advanced that there might be some direct relationship between them (I), (2). Later Drummond and Duliere, feeding carotene in ethyl oleate solution, concluded that there was no sign of growth promotion, and therefore carotene was not the provitamin. In 1928 certain Swiss investigators (3), (4), ( 5 ) again tried feeding carotene and obtained striking positive results, after noting the fact that the carotenoids and the vitamin gave similar color reactions with SbC12. Other workers verified these results (6). Ahmad (7) showed that the manner of feeding was most imnortant. Exnlanation of the neeative results of ~rum'mondand p hie re was found i n i h e fact that while carotene in fat solution was effective as a promoter or growth in vitamin A-depleted animals, in ethyl oleate solution i t is rapidly decolorized and decomposed. There appeared to he three possible explanations of carotene activity. F i s t , there might he traces of the vitamin present in carotene preparations. This possibility was discarded when i t became clear that while the vitamin shows three absorption maxima in the ultra-violet region of the spectra, carotene shows only two of these. Hence the absence of the vitamin can be assured. Second, it may be that more than one substance can function as the vitamin. This possibility seems to be borne out by the differences in stability toward heat and SOI, in color, and in potency VITAMIN A of preparations from differentsources. Karrer's recent As early as 1881 it was known that milk contained a work inclines him toward the belief that a specific factor necessary for nutrition. Yet it was not until grouping rather than a specific substance is responsible 192Cb22 that this factor, to which was assigned the for the activity. Thud, the carotene may be changed name vitamin A, was in any way related to the caro- to the vitamin in the animal body. There has been tenoids, those red and yellow substances found in much debate on this point, but i t now seems clear that this conversion does occur. Many investigators have * Presented in seminar to the Department of Organic Chemis- shown positive results, and Olcott and McCann (8) try of the Graduate School of Washington Square College, March claim to have shown conclusivelv that the conversion 2, 1932. 13
takes place in the liver. They have performed the conversion in vitro with liver extract from vitamin Adepleted rats, and since the conversion does not occur if the extract is first heated, they point out that the change is enzymatic in nature. In view of these facts, Karrer and his co-workers began the study of the structure of the carotenoids, and their results have been most interesting (9), (lo), (ll), ( m 03). Both carotene and its isomer lycopene are obtained in crystalline form. By analysis, we find C40Hm. On catalytic hydrogenation carotene proves to have eleven double bonds, and lycopene thirteen. The perhydrolycopene so formed is paraffinic in nature, and must therefore be acyclic. On ozonizing, acetic acid, some acetone, traces of succinic and oxalic acids are found, but no higher fatty acids and no ring compounds. Hence there may not be any long chain of saturated carbon atoms. Karrer believes that the chain is composed of eight isoprene residues, and six saturated carbons situated in the chain as shown in the formula which he proposes. '+
CHa
CHa
CH1
The saturated atoms lie within the molecule, a t either end, in pairs, and one at either end on the entire chain. Breaks at the ethylenic linkages account for the acetone (end of the chain) and acetic acid. The levuCH, CHa
a)
H$
-Y A
H3C
CHs
CHa I CHvCH, ~:[CHC:CH.CH:I4CH.* >CH* C=C CHa CHa CCHs
.
