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86 Stereochemistry

FIGURE 6 The D and L nomenclature for α-amino acids and aldohexoses. [Reprinted with permission from Eliel, E. L.,
and Wilen, S. H. (1994). “Stereochemistry of Organic Compounds,” Wiley, New York.]

several conventions have been developed to represent sional formula corresponding to the Fischer projec-
molecules (or rather their three-dimensional models) in tion, displays the staggered conformation in a three-
two dimensions. In one of them, the molecule is writ- dimensional, so-called “saw-horse” formula and its
ten with as many atoms as possible in the plane of the projection (seen from one end of the molecule) in a so-
paper and with additional atoms being connected with a called Newman projection. [This staggered representation
heavy line (—) when the attached ligand is in front of the is generated from the eclipsed one by rotation about the
plane and with a dashed line (- - -) when it is behind. In C(2)–C(3) bond.]
another, the so-called “Fischer projection” (after its origi-
nator Emil Fischer) the tetrahedron is oriented so that two
of the groups (top and bottom) are pointed away from the IX. DETERMINATION OF CONFIGURATION
observer, with the other two (sideways groups) pointing
toward the observer, and the molecule is projected in this Since configuration is an integral part of structure, the de-
fashion. Figure 6 shows Fischer projections of α-amino termination of the architecture of any molecule, naturally
acids and of monosaccharides (aldoses) with the further occurring or synthetic, is not complete until its configura-
proviso that the most oxidized group is to be placed at tion is known. For example, the fit of a drug with its recep-
the top and the NH 2 or OH and H ligands on the side. tor or of an inhibitor with an enzyme cannot be understood
In α-amino acids the symbol D is used when the NH 2 (or modeled, or rationally improved) absent information
group is on the right, L if it is on the left; it turns out that on its configuration.
all naturally occurring α-amino acids are L. In the case Configuration may be relative or absolute. To say that
of monosaccharides, the chiral center furthest away from a right hand fits a right glove is to make a statement of
the aldehyde or ketone function determines the descriptor the relative configuration of the two. Even a small child
and the symbol used is D when the OH is on the right in may be able to make this correlation. But to recognize
the Fischer projection formula, L if it is on the left, in- that a picture of a glove is that of a right glove in an
dependent of the configuration of any of the other chiral absolute sense is more difficult. The same applies to the
centers. determination of the absolute configuration (or sense of
The Fischer projection formulas shown above, while chirality) of a molecule.
useful for the assignment of the descriptors, do not corre- There are many ways of determining relative configu-
spond to the actual shape of most molecules. As explained ration (Eliel and Wilen, 1994). The most straightforward
belowunderthetopicofconformation,mostmoleculesex- one, where accessible, is an X-ray crystal structure; since
ist in “staggered” (Fig. 7) rather than the “eclipsed” con- an X-ray (or neutron or electron) diffraction picture leads
formations implied in Fischer projections. A more realis- to the positions of the constituting atoms in space, their
tic representation of, say, (R,R)-tartaric acid is shown in relative orientation (i.e., configuration) can be determined.
Fig. 7, which, in addition to the unrealistic three-dimen- Relative configuration thus correlates one chiral center

FIGURE 7 Fischer, sawhorse, and Newman representations of (2R,3R)-tartaric acid.