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ChemComm
Page 4 of 4
COMMUNICATION
Journal Name
direct study of a few samples, larger scale screening can
benefit from MISER analysis (multiple injections within a single
experimental run),22 where injections from a number of
different samples within a single chromatogram facilitates
visual comparison and the rapid selection of the best
performing reaction conditions. Rapid MISER SFC23 analysis
using a sample injection interval of 50 s afforded a convenient
high throughput analysis method with a plate time (time for
analysis of a 96 well microplate) of only 80 min. Two rows of
12 samples each are shown in Figure 4, with a number of
enzymes identified that afford not only good conversion but
also high enantioselectivity for the formation of either the (R)
and (S) product enantiomers (Table S3). Ultrafast chiral
chromatographic analysis is well suited to such first round in a
high-throughput mode, with conventional chromatographic
analysis often being used as a confirmatory assay.
DOI: 10.1039/C6CC08512A
Zavalij and M. P. Doyle, Chem. Sci., 2015, 6, 2196.
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9
W. Schafer, X. Bu, X. Gong, L. A. Joyce and C. J. Welch, in
Comprehensive Organic Synthesis, ed. C. J. Welch, Elsevier, Oxford,
UK, 2014, pp. 28-53.
D. C. Patel, M. F. Wahab, D. W. Armstrong and Z. S. Breitbach, J.
Chromatogr. A, 2016,
10 (a) O. H. Ismail, L. Pasti, A. Ciogli, C. Villani, J. Kocergin, S. Anderson,
F. Gasparrini, A. Cavazzini and M. Catani, J. Chromatogr. A, 2016,
Regalado, N. Wu and C. J. Welch, J. Chromatogr. A, 2014, 1363, 250;
(b) T. L. Chester, Anal. Chem., 2013, 85, 579.
11 (a) D. W. Robbins and J. F. Hartwig, Science, 2011, 333, 1423; (b) K.
Ohmatsu, N. Imagawa and T. Ooi, Nature Chem., 2014, 6, 47; (b) A.
Buitrago Santanilla, E. L. Regalado, T. Pereira, M. Shevlin, K.
Bateman, L.-C. Campeau, J. Schneeweis, S. Berritt, Z.-C. Shi, P.
Nantermet, Y. Liu, R. Helmy, C. J. Welch, P. Vachal, I. W. Davies, T.
Cernak and S. D. Dreher, Science, 2015, 347, 49; (c) M. T. Reetz, J.
Am. Chem. Soc., 2013, 135, 12480; (d) S. F. Dean, K. L. Whalen and
In conclusion, chromatographic enantioseparations taking less
than 1 minute can now be achieved for most racemic mixtures
using state of the art stationary phases, columns and
chromatographic equipment. Fast enantioseparations are also
possible with older instrumentation, with the use of relatively
inexpensive stationary phases packed into high efficiency short
columns. A simple and straightforward approach to method
M. A. Spies, ACS Cent. Sci., 2015, 1, 364.
development involves initial screening of
a variety of
13 (a) X. Zhang, J. Yin and J. Yoon, Chem. Rev., 2014, 114, 4918; K. W.
Bentley, Y. G. Nam, J. M. Murphy and C. Wolf, J. Am. Chem. Soc.,
2013, 135, 18052; (b) L. A. Joyce, E. C. Sherer and C. J. Welch, Chem.
stationary phases to identify a leading candidate, followed by
optimization of column length, flow rate and eluent
composition. The resulting ultrafast method can be used for
routine stereochemical analysis, or can form the basis for a
MISER method for high throughput analysis. While 5-30
minute methods for the chromatographic analysis of
enantiopurity are still used to support research investigations
in many synthetic chemistry, bioanalysis and pharmaceutical
research laboratories, in many cases these assays can be easily
replaced by much faster methods enabling ee analysis of over
one thousand samples in an 8 h workday. Consequently,
ultrafast chromatographic enantioseparations are expected to
greatly enable faster and more efficient research
investigations and the broader adoption of high throughput
experimentation approaches in stereochemical research.
Sci., 2014, 5, 2855; (c) H. H. Jo, C.-Y. Lin and E. V. Anslyn, Acc. Chem.
Res., 2014, 47, 2212.
14 Z. Pirzada, M. Personick, M. Biba, X. Gong, L. Zhou, W. Schafer, C.
Roussel and C. J. Welch, J. Chromatogr. A, 2010, 1217, 1134.
15 W. Schafer, T. Chandresekaran, Z. Pirzada, C. Zhang, X. Gong, M.
Biba, E. L. Regalado and C. J. Welch, Chirality, 2013, 25, 799.
16 C. L. Barhate, M. F. Wahab, Z. S. Breitbach, D. S. Bell and D. W.
Armstrong, Anal. Chim. Acta, 2015, 898, 128.
17 C. L. Barhate, Z. S. Breitbach, E. C. Pinto, E. L. Regalado, C. J. Welch
and D. W. Armstrong, J. Chromatogr. A, 2015, 1426, 241.
18 (a) E. L. Regalado, P. Zhuang, Y. Chen, A. A. Makarov, N. McGachy
and C. J. Welch, Anal. Chem., 2014, 86, 805; (b) E. Lemasson, S.
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Notes and references
1
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19 (a) E. L. Regalado and C. J. Welch, Trends Anal. Chem., 2015, 67, 74;
(b) J. M. Płotka, M. Biziuk, C. Morrison and J. Namieśnik, Trends Anal.
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Gasparrini, J. Chromatogr. A, 2015, 1383, 160; (d) X. Bu, E. L.
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Pharm. Biomed. Anal., 2016, 117, 316; L. Miller, J. Chromatogr. A,
2013, 1256, 261.
2
(a) E. L. Regalado and C. J. Welch, J. Sep. Sci., 2015, 38, 2826; (b) O.
H. Ismail, A. Ciogli, C. Villani, M. De Martino, M. Pierini, A. Cavazzini,
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M. F. Wahab, R. M. Wimalasinghe, Y. Wang, C. L. Barhate, D. C. Patel
and D. W. Armstrong, Anal. Chem., 2016, 88, 8821.
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4
5
C. J. Welch and E. L. Regalado, J. Sep. Sci., 2014, 37, 2552.
D. C. Patel, Z. S. Breitbach, M. F. Wahab, C. L. Barhate and D. W.
Armstrong, Anal. Chem., 2015, 87, 9137.
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D. Kotoni, A. Ciogli, C. Molinaro, I. D'Acquarica, J. Kocergin, T.
Szczerba, H. Ritchie, C. Villani and F. Gasparrini, Anal. Chem., 2012,
84, 6805.
20 M. F. Wahab, P. K. Dasgupta, A. F. Kadjo and D. W. Armstrong, Anal.
Chim. Acta, 2016, 907, 31.
(a) E. L. Regalado, M. C. Kozlowski, J. Curto, T. Ritter, M. G.
Campbell, A. R. Mazzotti, B. Hamper, C. D. Spilling, M. P. Mannino, L.
21 D. Kotoni, A. Ciogli, I. D'Acquarica, J. Kocergin, T. Szczerba, H. Ritchie,
C. Villani and F. Gasparrini, J. Chromatogr. A, 2012, 1269, 226.
22 C. J. Welch, X. Gong, W. Schafer, E. C. Pratt, T. Brkovic, Z. Pirzada, J.
F. Cuff and B. Kosjek, Tetrahedron: Asymmetry, 2010, 21, 1674.
23 K. Zawatzky, M. Biba, E. L. Regalado and C. J. Welch, J. Chromatogr.
A, 2016, 1429, 374.
Wan, J.-Q. Yu, J. Liu and C. J. Welch, Org. Biomol. Chem., 2014, 12
,
2161; (b) H. Lorenz and A. Seidel-Morgenstern, Angew. Chem., Int.
Ed., 2014, 53, 1218; (c) T. J. Ward and K. D. Ward, Anal. Chem., 2012,
84, 626; L. A. Joyce, E. L. Regalado and C. J. Welch, J. Org. Chem.,
4 | J. Name., 2012, 00, 1-3
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