International Journal of Organic Chemistry, 2011, 1, 215-217
doi:10.4236/ijoc.2011.14031 Published Online December 2011 (http://www.SciRP.org/journal/ijoc)
215
Proposed Extension to the Natta Projection Notation
System for Enabling an Indication of Relative
Stereochemistry and the Stereochemical St ate
Karel D. Klika
Department of C hemi st ry , University of Turku, Turku, Finland
Received October 1, 2011; revised November 6, 2011; accepted November 18, 2011
Abstract
A system of structure depiction, as an extension of the wedge and hashed wedge bonds (Natta projection),
and text notation is herein suggested that embodies more explicit information—or reduced over-statement as
circumstances warrant—on the stereochemical nature of the system at hand, in particular, for those cases
where only the relative stereochemistry of a compound is known.
Keywords: Stereochemistry, Stereochemical Descriptors, Natta Projection, Racemate, Enantiomer
The Natta projection system1 for indicating stereochem-
istry is familiar to all organic chemists, but surprisingly,
there are limitations in the depictions. For example, in
Figure 1, the structure presented for 1,2,4-trihydroxy-
cyclohexane is very exp licit: it represents the (1R,2S,4R)-
enantiomer. If this is the intended information to b e con-
veyed, then it is not only appropriate, it is also clearly
unambiguous. At the opposite end of the scale, the stru-
cture shown in Figure 2 is equally profound in its mean-
ing: nothing at all is known regarding the stereochemis-
try of 1,2,4-trihydroxycyclo hexane and the state could be
one or all or any mixture whatsoever of the eight possi-
ble stereoisomers.
Figure 1. The structural depiction of (1R,2S,4R)-1,2,4-tri-
hydroxycyclohexane.
Figure 2. The structural depiction of 1,2,4-trihydroxycy-
clohexane without any indication of stereochemistry.
Problems arise however, when a known mixture of
stereoisomers is present or the relative stereochemistry is
known but not the absolute configu ration. How does one
then represent the stereochemical state of the system?
For example, for a sample of known relative configura-
tion but unknown absolute configuration (irrespective of
whether one or two stereoisomers were present, pre-
sumably in the latter case a pair of enantiomers consti-
tuting a racemic sample), then clearly both Figures 1 and
2 do not suffice to accurately convey this information.
For Figure 1, because it can be both lacking2 (if two
enantiomers were present) and overstating (since the
absolute configuration is not known); for Figure 2, be-
cause it does not convey all the information that is
known. It thus seems curious that there is not a widely
used convention in place to conveniently address what is
a rather common occurrence. To alleviate this limitation
and to enable one to ascertain at a relative glance the
stereochemical state in more systems without the need to
scour the text for cor roborating or qu alifying info rmation,
the following extension to the Natta system is therefore
suggested.
For systems where something is known about the
stereochemistry b ut the information is inco mplete or there
is a need amalgamate data, the solid wedge and hashed
wedge bonds used to represent forward and backward
2Even if mention of this is made alongside the structural figure, in the
figure caption, or in the main body of the text one still has to locate and
retrieve it and, regretfully, all too often mention of this important as-
p
ect may even be neglec
t
ed altogether.
1Giulio Natta, 1903-1979.

K. D. KLIKA
216
oriented b onds, r espectively, are r eplaced analogously by
a hollow wedge bond and a hashed wedge bond with a
line through it, respectively3. For example, if the relative
stereochemistry of 1,2,4-trihydroxycyc lohexane is known
but the absolute configuration is unknown, then repre-
senting the structure as depicted in Figure 3 conveys this
notion succinctly.
Moreover, if the number of stereoisomers present in
the sample is known, this can be indicated by an integer
number in italics near to the questionable stereochemical
bond associated with the lowest carbon atom number. If
the number of stereoisomers is unknown, this can be
indicated by the abbreviation “unk”; if the sample is ra-
cemic, then the abbreviation “rac” can be applied (due
the presence of three stereogenic centers in the particular
example at hand, a “2” does not unambiguously equate
to a racemate); and if the sample is holemic (i.e. enan-
tiopure), this can be indicated by the abbreviation “hol”
(needless to say, a “1” would necessarily be equivalent).
For the example chosen, “cis” and “trans” can also indi-
cate relative stereochemistry, but do not infer anything
regarding the number of stereoisomers, and the notation
is limited in the main to only two or three stereogenic
centers. Furthermore, the enantiomeric content4 (ec) of
the sample can be indicated by a real number in lieu of
an integer if the sample is scalemic (or if the use of enan-
tiomeric excess (ee) is preferred, this can be alternatively
indicated by a percentage to distinguish it from the ec).
For cases other than scalemates where only two stereoi-
somers are unambiguously present, the real number will
indicate the proportion of the two stereoisomers. If the
major stereoisomer is known, this can be indicated by
use of the new bond indicators (a hollow wedge bond
and a hashed wedge bond with a line through it).
The number system can also be applied to wavy bonds
to eliminate ambiguity. In Figure 4, the replacement of
the stereochemically explicit bonds for the groups at po-
sition 1 for the example at hand may alternatively be
used to indicate either a pair of C-1 epimers or just one
stereoisomer of unknown stereochemistry at C-1. The
ambiguity is simply resolved by the incorporation of a
number. Other examples of the notation are also given in
Figure 4.
This notational system is readily useab le in exactly the
same manner within the general nomenclature, so in ad-
dition to the conventional “()-” or “(ra c)-” preceding a
name to indicate a racemic mixture, so too can “(1)-”,
“(2)-”, “(0.8)-”, or “(80%)-” etc. be used to indicate the
presence of a single stereoisomer, two stereoisomers, an
80% ec, or an 80% ee mixture, respectively. If the major
isomer is unknown, this can appropriately be indicated
Figure 3. Depiction of the extension of the Natta projection
system for a sample of 1,2,4-trihydroxycyclohexane of kno-
wn relative stereochemistry but unknown absolute confi-
guration.
Figure 4. For 1,2,4-trihydroxycyclohexane, the structure depicted in (a) explicitly indicates the presence of a single stereoi-
somer of unknown configuration at C-1 (alter natively, a “2” would indicate the presence of a pair of C-1 epimers), whilst the
structure depicted in (b) explicitly indicates the presence of a pair of C-1 epimers consisting of the main stereoisomer,
(1R,2S,4R)-1,2,4-trihydroxycyclohexane, in 60% content and the minor stereoisomer, (1S,2R,4S)-1,2,4-trihydroxycyclohexane,
in 40% content. For the structure depicted in (c), the relative stereochemistry is known but the number of stereoisomers is
unknown (i.e. the sample could be holemic, racemic, or scalemic). For the structure depicted in (d), the sample is scalemic and
is composed of 80% (1R,2S,4R)-1,2,4-trihydroxycyclohexane and 20% (1S,2R,4S)-1,2,4-trihydroxycyclohexane. The names
beneath the structures reflect the stereochemical states depicted and are a direct extension of the notation to the general no-
menclature. Additional explanation on the nomenclature notation is given in the ensuing paragraph.
color options were not considered since color is not yet ubiquitous and
half-tone was considered too in d i stinct and dependent on print quality.
4The recommendation of Gawley [1] is preferred with regards to the
use of enantiomeric composition (ec as the percentage of one enanti-
omer) over enantiomeric excess (ee).
3Selection was based on avoiding confusion or contradiction with
established notation for other purposes, or similar purposes especially,
and with notations already available in drawing programs. Similarity,
though with clear distinction, to the Natta projection bonds was also
sought. Thus bold, hashed, and dashed bonds were not chosen whils
t

217 K. D. KLIKA
by asterisks appended to the R and S descriptors; if
known, then this can be indicated by the use of under-
scores. Additional descriptors can include “(hol)-” for
holemic, “(scl)-” for scalemic (where the ec is between
50% - 100%), and “(unk)-” for an unknown number of
stereoisomers. Of note, it has always been ambiguous
when “R*” etc. (or RS etc.) has been used as to whether
one or more stereoisomers is present based on the name
alone and the use of numbers readily eliminates this
limitation. For the examples given in Figure 4, the cor-
responding names are given within the figure.
In summary, an extension of the conventional Natta
projection system to indicate stereochemistry has been
formulated as an aid to better describing the stereo-
chemical state of a system. Adoption of the notation may
reduce the level of confusion or misunderstanding in the
mind of a reader since there is an ever increasing need to
rapidly peruse the output of database searches or volu-
minous compilations of papers with efficacy. In light of
the importance of stereochemistry in biological systems
and the stereochemical dependence of drug activity [2],
this is of paramount significance.
Acknowledgements
Financial support of this work by Turun Yliopistosäätiö
is gratefully acknowledged.
References
[1] R. E. Gawley, “Do the Terms ‘% ee’ and ‘% de’ Make
Sense as Expressions of Stereoisomer Composition or
Stereoselectivity?” The Journal of Organic Chemistry,
Vol. 71, No. 6, 2006, pp. 2411-2416.
doi:10.1021/jo052554w
[2] J. Caldwell, “The Importance of Stereochemistry in Drug
Action and Disposition,” The Journal of Clinical Phar-
macology, Vol. 32, No. 10, 1992, pp. 925-929.