A Panoramic Approach to the
D a v i d H. RosenblaH' John Hopkins University Baltimore, Maryland
Proof of Configuration of Aldohexoses
M o s t st,udents of introductory organic chemistry comprehend the st,ereoisomerism of sugars without undue difficulty, yet they seldom grasp the classical proofs of configuration. This may possibly be due t,o the practice of presenting the evidence piecemeal inst,ead of providing a panoramic view. The present didactic approach has been developed to supplement the textbook description2 of Emil Fischer's brilliant work on the elucidation of the relative configuration of glucose. Each of the experimental tests developed by Fischer ~ieldeda decision between two alternatives, in essence an answcr of yes (Y) or no (N); of or -; of 1 or 0. The results of a particular sequence of such tests on any given sugar might have been condensed to a series of symbols chosen from a pair; for example, YYNY. Provided the proper sct of tests had been chosen, a unique "code word" of this type could have been associated with each aldohexose configuration. Such a reduction to a two-symbol code is essent,ially the assigument of a number in the binary system of arithmet,ic. Fischer was concerned with the eight relative configurations, rather than with the sixteen possible absolute configurations of the aldohexoses; thus, ideally, a t,hree-digit code should have sufficed, i.e., zero through seven in the binary syst,em. In actuality, the distribution of alternatives was not. always even (four aud four), so that four sets of tests were required. For the purposes of panoramic presentation, it is init,ially assumed that the investigator has a t his disposal samples of all 16 aldohexoses, to which configurations are to be assigned. He is able t,o establish pairs of epimers through degradation of the hexoses to pent,oses; he can oxidize all of the hexoses, as well as the penloses derived by degradat,ion, to corresponding dibasio acids; and he can test the dibasic acids for opt,iral activity. The four criteria for identification are embodied in the following questions:
+
I s the saeeharic acid deriued from the bezose i n question optically active? Is the saeeharic aeid derived from the hezose i n question idatical to the saceharie aeid derived j m m any of the other 15 nlrlohezoscs? (o-mannose, kmannose, u-idose and Lidose give unique sacehario acids, whereas the following pairs yield identical saceharic acids: D- and L-dose; u- and irg;nlacto8e; o-glucose and ~ g u l o s e ;D-guhe and riglucoae; o-altrose and D-talnse; L-altroseand L-tdose.) Is the saccharic acid derioed from the epimer of the hezose i n question optically active? Is the frihyd~ozyglzrlarie aeid ohtained from the pentose degmdation prodort of the hems? in question optically actiue?
(code word) is unique for each aldohexose; that is, each sugar is uniquely defined by the series of experiments. Furthermore, the yes-no code can be translated into binary numbers, and thence into their decimal system equivalents. I t is possible to see the entire picture a t a glance. A consequence of the incomplete use of the binary code is that it is not really necessary to perform all tests for each aldohexose, provided that one epimer of each pair is fully established. This is fortunate, since it provides an alternative to testing all 16 aldohexoses as a means of establishing the identity of the mannoses and idoses, as required by Question (2). Having est,ablished the over-all logic of Fischer's approach, t,he instructor is free to explain how it was possible to proceed with structure proofs, even though several of the 16 sugars were unavailable. Thus, Fischer circumvented the lack of gulose by synthesizing it from glucaric (glucosaccharic) acid t,o complete the study of the configuration of glucose. This panoramic approach makes it evident to the student that the t,ext,bookcase of glucose is not merely a happy accident in the history of chemistry, but illustrates a principle of widespread applicability. I t also serves to demonstrate the fundamental clarity of a system easily obscured by essent,ial hut secondary details. Code W o r d Key to Aldohexose Structures
Name of sugar
Code word answers to Configuration questions" ( U Series) 1 2 3 4
Binary equivalent Decimal of code word equivalent
N N Y N
0010
2
Y N N N
1000
8
Glucose
Y N Y Y
1011
11
Mannose
Y Y Y Y
1111
15
Gulase
Y N Y N
1010
10
Idose
Y Y Y N
1110
14
N N Y Y
0011
3
Allase
Altrose
The answer to each question will be a clear yes or no. I t may be seen in the table that. the answer pattern
Galactose
'Faculty of the Evening College of Johns Hapkins Univ. ~ ~ o ~ u u s O N ,R . R. and BOYD,11. N. "Organic Chemistry," Allyn :md Bacon, Inc., Boston, Mass., 1959, p. 761.
Talose
'E $
f
e
9
'See questions in text. Volume 42, Number 5, May 1965
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