Anal. Chem. 2009, 81, 10215–10226
Development of New HPLC Chiral Stationary
Phases Based on Native and Derivatized
Cyclofructans
Ping Sun, Chunlei Wang, Zachary S. Breitbach, Ying Zhang, and Daniel W. Armstrong*
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019
An unusual class of chiral selectors, cyclofructans, is
introduced for the first time as bonded chiral stationary
phases. Compared to native cyclofructans (CFs), which
have rather limited capabilities as chiral selectors, ali-
phatic- and aromatic-functionalized CF6s possess unique
and very different enantiomeric selectivities. Indeed, they
are shown to separate a very broad range of racemic
compounds. In particular, aliphatic-derivatized CF6s with
a low substitution degree baseline separate all tested
chiral primary amines. It appears that partial derivatiza-
tion on the CF6 molecule disrupts the molecular internal
hydrogen bonding, thereby making the core of the mol-
ecule more accessible. In contrast, highly aromatic-
functionalized CF6 stationary phases lose most of the
enantioselective capabilities toward primary amines, how-
ever they gain broad selectivity for most other types of
analytes. This class of stationary phases also demonstrates
high “loadability” and therefore has great potential for
preparative separations. The variations in enantiomeric
selectivity often can be correlated with distinct structural
features of the selector. The separations occur predomi-
nantly in the presence of organic solvents.
polysaccharide-based CSPs,2-11 macrocyclic antibiotic CSPs,12-22
and π complex CSPs.23-26 Researchers continue to make great
efforts to develop new HPLC CSPs, which could make a substan-
tial impact on enantiomeric separations. It has been stated that
today in order for any new CSPs to have an impact, they must
fulfill one or more of the following requirements:27 (a) broader
applicability than existing CSPs, (b) superior separations for
specific groups of compounds, or (c) fill an important unfulfilled
separation niche. In the present article, a unique class of CSPs
based on cyclofructan (CF) is introduced and is shown to have
the potential to satisfy all of the above-mentioned requirements.
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Chirality 2001, 13, 648–656
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Enantiomeric separations have attracted great attention in the
past few decades. Early enantioselective LC work in the 1980s
provided the impetus for the 1992 FDA policy statement on the
development of stereoisomeric drugs.1 This was because the facile
analysis and preparation of many pharmaceutically active enan-
tiomers became possible for the first time. Such broadly applicable
techniques were essential for pharmacokinetic and pharmacody-
namic studies, development, quality control, and sometimes
production of enantiomeric drugs. HPLC with chiral stationary
phases (CSPs) is far and away the most powerful and widely used
technique for solvent-based enantiomeric separations at both
analytical and preparative scales. Supercritical fluid separations
are increasing in importance, particularly for preparative separations.
Currently, over a hundred CSPs have been reported, and these
CSPs are made by coating or bonding the chiral selectors, usually
to silica gel supports. Interestingly, only a few types/classes of
CSPs dominate the field of enantiomeric separations, for example,
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(26) Gu¨bitz, G.; Schmid, M. G. Chiral Separations: Methods and Protocols; Methods
in Molecular Biology, Vol. 243; Humana Press: Totowa, NJ, 2004; pp 1-
432.
* To whom correspondence should be addressed. Phone: (817) 272-0632. Fax:
(817) 272-0619. E-mail: sec4dwa@uta.edu.
(27) Wang, C.; Armstrong, D. W.; Risley, D. S. Anal. Chem. 2007, 79, 8125–
(1) Anon. Chirality 1992, 4, 338-341.
8135.
10.1021/ac902257a 2009 American Chemical Society
Published on Web 12/14/2009
Analytical Chemistry, Vol. 81, No. 24, December 15, 2009 10215