January 19, 1917] 



SCIENCE 



53 



titles. This striking difiference between the 

 natural and the laboratory synthesis has 

 attracted much attention and extended in- 

 vestigations have been made in recent years 

 to solve the mystery. Nevertheless, the 

 problem of building up from its elements 

 the dextro or the levo form alone or the one 

 form in excess of the other so that the re- 

 sulting product is optically active, remains 

 to-day as in the beginning, an unsolved 

 problem. 



While the synthesis of either the dextro 

 or the levo form alone of an asymmetric 

 compound from its elements or from op- 

 tically inactive materials has never been 

 accomplished, nevertheless, it is entirely 

 possible to build up an asymmetric com- 

 pound if we employ another already exist- 

 ing optically active compound as an agent 

 for effecting the synthesis. That such a 

 procedure is possible was shown by Fischer 

 in 1889 in the course of his celebrated in- 

 vestigations on the sugars. It had long been 

 known that the so-called aldose sugars com- 

 bine directly with hydrocyanic acid. This 

 addition introduces a new asymmetric car- 

 bon atom into the compound : 



,H yB. /OH 



R— C— O-FHCN^R-C-CN and R-C-CN 



OH H 



I. n. 



We might naturally expect that the two 

 possible forms (I. and II.) of the new 

 asymmetric group will be produced in 

 equal amounts. Fischer found, however, 

 that when hydrocyanic acid combines with 

 (Z-glucose, both forms of the resulting 

 cyanogen derivative are indeed obtained, 

 but that the one form is obtained in excess 

 of the other. When the action is carried 

 on with cZ-mannose the one form only is 

 produced. This result is readily explained 

 upon the very reasonable assumption that 

 the manner of the addition of the hydro- 

 cyanic acid to the sugar molecule is influ- 



enced by the forces exerted by the asym- 

 metric groups already present in the sugar 

 molecule. In the absence of such modifying 

 forces, that is, in compounds which do not 

 contain asymmetric groups, the two pos- 

 sible forms are produced in equal quan- 

 tities, but in the presence of such asym- 

 metric groups the two forms may be pro- 

 duced in unequal amounts. 



Now it will readily be noticed that this 

 observation of Fischer suggests a possible 

 way of effecting the synthesis of an op- 

 tically active body from its constituent ele- 

 ments. For example, if one could find 

 some method for splitting off from the mol- 

 ecule, the new asymmetric carbon group 

 added to d-mannose in such a way that the 

 resulting compound would contain this 

 asymmetric group, then it is evident that 

 the compound so produced would be op- 

 tically active since it would consist of the 

 one form only. Thus a synthesis of an op- 

 tically active compound would have been 

 effected, although it would have been made 

 possible through the influence of a previ- 

 ously existing optically active compound. 



While it has not been found possible to 

 split off the newly formed asymmetric 

 group resulting from the addition of hydro- 

 cyanic acid to d-mannose, nevertheless the 

 synthesis of a number of optically active 

 compounds has been accomplished through 

 the application of this general principle. 

 Such a synthesis is generally termed an 

 asymmetric synthesis. However, such a 

 synthesis, accomplished as it is through the 

 assistance of an already existing optically 

 active compound, is only partial and I shall 

 designate it in the discussion that follows 

 as a partial asymmetric synthesis. This 

 term, as I shall use it, signifies the synthesis 

 of either the dextro or levo form alone, or 

 of the two forms in unequal amounts, 

 effected through the assistance of an already 

 existing optically active compound. It is 



