Tetrahedron xxx (2016) 1e5

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Tetrahedron
journal homepage: www.elsevier.com/locate/tet

Theoretical investigation of the relationship between four-carbon

D-sugars and five L-amino acids

Dan Zhao a, Qi-Qi Zhao a, Hua-Jie Zhu a, *, Li Liu b

a
Chinese Center for Chirality, School of Pharmacy, Hebei University, 071002, Baoding, China
b
Health Science Center, Hebei University, 071002, Baoding, China

a r t i c l e i n f o a b s t r a c t

Article history: This study constructed the relationship between L-amino acids and four-carbon D-sugar using quantum
Received 4 July 2016 theory. Theoretically, an L-amino acid could react with the ketone to afford the corresponding Schiff base
Accepted 15 July 2016 which may take place an Aldol reaction with a molecule of formaldehyde. An assumption is proposed
Available online xxx
that the Aldol addition products with (R) or (S) configuration could have different quantity due to the
effect from stereogenic center of L-amino acid. By hydrolysis of the Aldol addition, different D- or L-sugar
Keywords:
would form. Thus, B3LYP, WP1MPW91 and wB97XD theories were used for the energy difference
D-Sugar
computations at the 6-311þþG(2d,p) level in the gas phase, or in water using PCM and SMD model,
L-Amino acids
Conformational study
respectively. The predicted ee value sequence agrees well to the experimental result in the asymmetric
Energy difference synthesis of 3-carbon sugar using five L-amino acids. Further theoretical study exhibited that 4-carbon D
DFT sugar should form if the corresponding L-amino acid is used. The ee values of the 4-carbon sugar are
bigger than those of 3-carbon D-sugars catalyzed by the same L-amino acids. This looks like the chiral
amplification in the procedure.
Ó 2016 Elsevier Ltd. All rights reserved.

1. Introduction be enriched by amplification,8 for example, via different solubility

of salts of D-, L-amino acid crystals; or the different solubility of
Until now, researchers don’t know the relationship between an ribonucleosides produced the chiral amplifications.9
L-amino acid and a four-carbon D-sugar. An L-amino acid is the key Recently, Breslow and co-workers reported that some meteor-
synthetic unit to protein, and the D-sugar is the important material itic components can be used to furnish normal L-amino acids,
to afford cellulose, also the energy sources for life use. Formation of D-sugars and nucleosides, in high chiral excess under sensible
both L-amino acids and D-sugars in the origin of life has puzzled and prebiotic conditions.4,10 For example, when a pure L-valine (4) was
attracted many scientists to explore it, such as Cech’s study (RNA used, 5.4% ee of three-carbon D-sugar (8) formed from formalde-
first, where RNA can act as a substrate and/or an enzyme);1 and hyde (6) (Scheme 1), this ee value increased to 19.2% under the pH
protein-mediated for evolution et al.2
It is reported that five (S)-a-methyl amino acids (L-type) with ee
values from 2.8% to 15.2% were found in meteorites that landed on
Earth near Murchison Australia in 1969,3 they have a chiral qua-
ternary carbon instead of tertiary carbon, which exhibits the ster-
eogenic center could not take racemization. The abnormal amino
acids may play a role in formation of normal L-amino acids or D-
sugars due to its weak catalysis.4 Other discoveries included the
right polarized UV light from the universal led to selective de-
struction of D-amino acids, resulting in a mixture with a few per-
cent excess of the L-enantiomer,5 or the polarized UV from neutron
stars.6 Breslow and co-workers studied the conversion of (S)-a-
methyl amino acids to normal L-amino acids with about 1% ee
values catalyzed by Cu(II),7 and this small ee of L-amino acids may

Scheme 1. (left in dash frame) Formation of three-carbon sugar (8) from CHO; (right)
* Corresponding author. E-mail address: zhuhuajie@hotmail.com (H.-J. Zhu). L-amino acids used in the chiral catalytic formation of 8.

http://dx.doi.org/10.1016/j.tet.2016.07.047
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

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2 D. Zhao et al. / Tetrahedron xxx (2016) 1e5
values of 2.9e4.2. L-Glutamic acid (5) led to 21.4% ee formation of 8
or 34.8% under the same acidic conditions. Under the prebiotic
conditions, the atmosphere contained huge CO2, which could dis-
solve in water and lead to water having about pH value of 5.6. This
datum is smaller than 4.2 but larger than 6.5. Thus, this weak acidic
condition could be a good benefit to synthesize D-sugar in prebiotic
environment.
This discovery is extremely important and valid. A logical
question then rises: should the other D-sugars such as 4-carbon
sugar could form via the similar procedure? However, there is no
any experimental or theoretical investigation to show asymmetric
formation of four-carbon sugar (C4H8O4, 9) or others catalyzed by L-
amino acids. In this study, we investigate the asymmetric formation
of four-carbon sugar catalyzed by different L-amino acids. The
prediction clearly exhibits that high ee values of four-carbon sugar,
theoretically, could be obtained using the corresponding L-amino
acids, such as phenylalanine.
2. Theoretical section
Theoretically, an L-amino acid could react with hydroxyl acet-
aldehyde (7) to form the corresponding Schiff base 12 (Scheme 2).
The second CHO molecule would react with the intermediate 12 to
afford 13 with either (R) or (S) configuration at C-2 in different ratio,
which would depend on the both of (1) their relative energy dif-
ferences and the (2) Aldol reaction activation energy barrier. Base
on the reports from Breslow,4,10 the Aldol reaction could take place
at room temperature to afford 13, that means the activation ener-
gies (DG1 and DG2 in Fig. 1) are not high. Therefore, this Aldol re-
action is reversible at room temperature. The distributions of
products (2R,20 S)-13 and (2S,20 S)-13 should majorly depend on
their energy differences (DE in Fig. 1). The bigger the relative energy
difference is, the bigger the quantity difference of (2R,20 S)-13 and
(2S,20 S)-13 should be. Namely, the higher the de value will be. After
Scheme 2. Formation of three-carbon sugar (8) catalyzed by L-amino acids.
Fig. 1. Coordinates for plausible reaction paths from mixture of 12 and CH2O to 13. Herein, (R)-13 and (S)-13 are used, respectively, to representative (2R,20 S)-13 and (2S,20 S)-13. Two
cases exist in the procedure. Case 1: the reaction barrier (DG2) to (S)-13 is higher than that to (R)-13 (DG1); case 2: the reaction barrier (DG2) to (S)-13 is smaller than that to (R)-13
(DG1). Since the sugar obtained has D-type of AC, the product (S)-13 should have lower relative energetics than (R)-13.
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the Aldol addition, this intermediate 13 could decompose into the
corresponding D- or L-sugar 8 and the L-amino acid in water, re-
spectively. Thus, the de values of 13 should be the same as ee values
of the sugar 8. In this report, activation energy barriers are not
considered since the reaction could take place at room tempera-
ture. For a clear statement, (R)-13 and (S)-13 are used, respectively,
to representative (2R,20 S)-13 and (2S,20 S)-13, and the de values of
the intermediate 13 should be regarded as the ee values of the
corresponding D-sugar.
3. Computational section and discussion
The calculations were performed using density functional the-
ory (DFT),11 because energies,12 analytic gradients, and true analytic
frequencies,13 are available for all DFT models. We used the B3LYP,14
WP1MPW91,15 and wB97XD16 theories at the bases sets of 6-
311þþG(2d,p) in calculations.17 Frequency calculations were also
performed.18 Solvent effects were modeled through the use of the
polarizable continuum model (PCM)19 and solvation model density
(SMD),20 respectively. In our recent study, the methods mentioned
above exhibited valid data to explain the experimental data by
conformational study.21
The conformations of (R)-13 and (S)-13 were searched using
different conformational search packages, such as ComputeVOA,
Barista, respectively, via MMFF94S force field. All conformations
that were found were used in optimizations at the B3LYP/6-31G(d)
level in the gas phase first. These geometries with relative energy
from 0 to 2.5 Kcal/mol were used for further optimizations using
five different quantum methods. The first one is to optimize the
B3LYP/6-31G(d)-conformations at the B3LYP/6-311þþG(2d,p) level
in the gas phase (method 1). The second one is to use the B3LYP/6-
311þþG(2d,p)-optimized geometries in optimizations at the same
level in water using PCM model (method 2). The third method is to
optimize the B3LYP/6-31G(d)-geometries at the WP1PW91/6-
311þþG(2d,p) level in the gas phase (method 3), and then these
WP1PW91/6-311þþG(2d,p)-optimized conformers were re-
computed at the same level in water using PCM model (method
4). Finally, the geometries were then optimized at the wB97XD/6-
311þþG(2d,p) level in water using SMD model (method 5). The
smallest energy differences between (R)-13 and (S)-13 were then
computed using the lowest energy of (R)-13 and (S)-13. Every
method can afford its corresponding smallest energy difference.
Then, the differences were used for quantity computations of (R)-13
and (S)-13, respectively, using Arrhenius Eq. 1.
Q ¼ keDE=RT (1)
where Q is the quantity of intermediate (R)-13 or (S)-13, k is
a constant, R is the gas constant (8.314 J mol1 k1), T is the ab-
solute temperature, 298 K is used in the calculations. DE is the
 D. Zhao et al. / Tetrahedron xxx (2016) 1e5 3

energy difference. Then, the ratio of (S)-13 to (R)-13 should be values were 12.1%, 22.1% and 6.2% using the total electronic energy,
computed using Eq. 2: zero point energy and Gibbs free energy, respectively. The experi-
mental ee was 5.4%, or 19% under the acidic condition
QS eDES =RT (pH¼2.9e4.2). Method 4 predicted well for (R)-13 using L-valine (4)
¼ DE =RT ¼ eðDES DER Þ=RT (2)
QR e R using the three kind of energies, especially using Gibbs free energy
in ee predictions (6.2% predicted vs 5.4% in experiments). Another
On the other hand, the sum of fractions of (R) and (S)-isomers
good prediction way is method 1 by using Gibbs free energy, the
should be 1 (Eq. 3):
predicted ee value is 7.7% (entry 11), and the experimental ee was
QS þ QR ¼ 1 (3) 5.4%. Methods 1 and 3 cannot predict the accurate energy differ-
ences. Among all five computational methods, method 5 gave the
Combinational uses of Eqs. 2 and 3, we can compute the de poorest prediction, for example, only the predicted ee value
values for (R)-13 and (S)-13 for each method. The results are (smallest ee is 12.1%) for L-alanine (1) closed to the experimental ee
summarized in Table 1. % (1.6%), other predictions did not match the experimental results
(Table 1, entries 10, 15, 20 and 25).
Table 1 It was found that L-type sugar might produce under weak basic
The relative energy of intermediate (R)-13 and (S)-13 and the predicted ee for condition (pH¼8e9) or neutron condition (pH¼6.5e7.5) with
D-sugar 8 and experimental ee values a small ee value.4 However, this reaction system could be of a weak
Entry Amino Method DE(SeR) of 13 (kcal/mol) Calcd ee (%) for 8e Exp. acidic environment since the formation of Schiff base (12) led to the
acid ee (%) relative strong conjugation formation of lone pair of electrons of N
DETa DE0 DG DET DE0 DG
atom to the sp2 C, which can reduce the base of N atom. Thus, the
1 1 1 0.396 0.448 0.158 32.3 36.2 13.3 1.6b
whole molecule should exhibit weak acidic. This is helpful forma-
2 2 0.132 0.126 0.165 11.1 10.7 13.9
3 3 0.098 0.282 0.424 8.3 23.4 34.4 tion of D-type sugar.
4 4 0.138 0.153 0.250 11.6 12.9 20.8 It is amazing that the predicted product should be L-sugar using
5 5 0.220 0.144 0.420 18.4 12.1 54.4 L-glutamic amino acid and L-serine (Table 1, entries 6e10 and
6 2 1 1.439d 1.119 1.027 83.9 73.8 70.0 0.6b 21e25). These are conflict to the experimental results. Why only
7 2 1.273 0.618 0.569 79.2 48.0 44.7
8 3 1.459 1.091 0.301 84.4 72.7 24.9
the two predictions disagree with the experimental results? The
9 4 1.515 0.825 0.390 85.7 60.3 31.8 possible reason may be the characteristics of the two amino acids.
10 5 1.168 0.916 0.649 75.6 64.9 50.0 For example, serine (5) has a terminal eOH and glutamic amino
11 3 1 0.618 0.504 0.091 48.0 40.2 7.7 5.4b acid (5) has a eCOOH. Both groups easily form H-bonds with other
12 2 0.548 0.520 0.725 43.3 41.3 54.6
terminal eOH in intermediate 13, affording a big head-tail con-
13 3 0.898 0.564 0.707 100.0 44.4 53.5
14 4 0.645 0.511 0.884 49.7 40.7 63.4 nection cyclic structure when conformational search is performed
15 5 0.705 0.343 0.393 53.4 282 32.1 (Fig. 2). Such a big cyclic structure is not easily formed under water
16 4 1 0.219 0.222 0.127 18.3 18.6 10.7 5.4b since the huge number of water molecules could break down the
17 2 0.178 0.143 0.395 15.0 12.1 32.2 19.0c head-tail connected circle. For example, it should be a 9-atom ring
18 3 0.269 0.139 0.450 22.4 11.7 36.3
19 4 0.144 0.265 0.074 12.1 22.1 6.2
structure in the intermediate 13 using L-serine and 11-atom ring
20 5 0.277 0.355 0.294 23.0 29.1 24.3 structure using L-glutamic amino acid, respectively (Fig. 2). The
21 5 1 1.993 2.048 1.757 93.3 93.9 90.2 21.4b formation of H-bonds may change the energy sequence of (R)-13
22 2 1.829 1.757 1.176 91.3 90.2 75.9 34.8c and (S)-13. Other amino acids, such as L-alanine (1) L-phenylalanine
23 3 1.680 2.037 1.785 89.0 93.8 90.7
(3) and L-valine (4) had no any terminal eOH or eCOOH, they could
24 4 2.767 1.920 1.392 98.2 92.5 82.6
25 5 2.726 2.730 2.875 98.0 98.0 98.5 not form such big head-tail connected structures in 13. The energy
sequences predicted using these L-amino acids agree to the ex-
a
DET: Total electronic energy difference. DE0: Zero-point energy difference. DG:
Gibbs free energy difference.
perimental results. Therefore, the real head-tail connection struc-
b
See Ref. 10 for details, the pH values were not mentioned in this reference. ture may not exist in real case. To examine the assumption, the
c
pH values in reactions were from 2.9 to 4.3. See Ref. 4 for more details. lowest energy geometries of (R)-13 and (S)-13 using L-glutamic
d
The italic data means the results do not agree to the experiments. amino acid and L-serine were analyzed (Fig. 2). As the expected,
e
The ee values of D-sugar 8 equal to the de values of 13.
both (R)-13 and (S)-13 using L-glutamic amino acid formed the
headetail connected circle with two H-bonds. (R)-13 using L-serine
As mentioned above, the de values of 13 should be the same as formed head-tail connected structure with one H-bond while (S)-
the ee value of sugar 8 obtained in experiments. Therefore, the de 13 did not form H-bond using L-serine. Obviously, the ring sizes of
values of 13 should be used as the ee values of D-sugar in the fol- 9-atom could be easily broken in water environment.
lowing discussion. The best prediction is to use method 2 to predict If all of the head-tail connected structures using L-serine and L-
the ee values of sugar 8 catalyzed by L-valine. The predicted ee glutamic acid are removed from the energy computations and

Fig. 2. The cyclic head-tail connection structures of (R)-13 and (S)-13 catalyzed by L-glutamic amino acid and L-serine.

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4 D. Zhao et al. / Tetrahedron xxx (2016) 1e5

analysis, the energy difference sequence of (R)-13 and (S)-13 may 15, respectively, for each computational method. The results are
reversed. Therefore, all of the conformations without the head-tail summarized in Table 3.
connections were used in the computations using the four
methods. The calculation results are listed in Table 2. Fortunately, Table 3
the predicted sugar should be D-type using L-serine now, its ee Predicted relative energy of (R)-15 and (S)-15 and their ee values for D-sugar 10
value was 11% (entry 3, Table 2), the experimental value is only 0.6. catalyzed by the five L-amino acids
The D-sugar was also predicted with ee values of 34e95% catalyzed Entry Amino acid Method DE(SeR) of 15 (kcal/mol) Calcd ee (%) for 10b

Table 2 DET DE0 DG DET DE0 DG

The relative energy differences of intermediate 13 with (R) or (S) configuration at C-2 1 1 1 0.628 0.331 0.564 48.6 27.3 44.4a
catalyzed by L-glutamic amino acid and L-serine, respectively 2 2 1.956 1.653 0.389 92.9 88.5 31.7
3 3 0.564 0.330 0.670 44.4 27.2 51.3
Entry Amino Method DE(SeR) of 13 (kcal/mol) Calcd ee (%) for 8 Exp.
4 4 1.885 1.600 0.469 92.1 87.5 37.7
acid ee (%)
DET DE0 DG DET DE0 DG 5 5 1.251 0.873 0.247 78.5 62.8 20.6
6 2 1 0.038 0.049 0.759 3.3 4.2 56.6
1 2 1 0.913 0.800 0.349 64.8 58.9 28.7 0.6a
7 2 0.107 0.116 0.639 9.0 9.8 49.3
2 2 0.785 0.746 0.452 58.1 55.8 36.4
8 3 0.788 0.651 0.108 58.2 50.1 9.2
3 3 1.298 1.217 0.656 79.9 77.3 50.4
9 4 0.486 0.415 0.120 38.9 33.7 10.1
4 4 0.873 0.777 0.331 62.8 57.6 27.3
10 5 1.296 1.394 1.289 79.9 83.7 79.7
5 5 1.776 1.080 0.452 90.5 72.2 36.4
11 3 1 1.221 1.087 1.209 77.5 72.5 77.1
6 5 1 0.053 0.069 0.624 4.5 5.8 48.4 21.4a
12 2 1.336 1.216 0.104 81.1 77.3 8.8
7 2 0.216c 0.358 0.527 18.0 29.4 41.8 34.8b
13 3 0.769 0.973 1.740 57.2 67.7 90.0
8 3 0.028 0.055 0.218 2.3 4.7 18.2
14 4 0.726 0.967 1.784 54.7 67.4 90.6
9 4 0.175 0.233 0.355 14.7 19.5 29.1
15 5 0.386 0.435 0.067 31.5 35.2 5.6
10 5 0.371 0.242 0.274 30.4 20.1 22.8
16 4 1 0.240 0.193 0.377 20.0 16.2 30.9
a
See Ref. 10 for details, the pH values were not mentioned in this reference. 17 2 1.750 1.260 0.116 90.1 78.8 9.8
b
pH values in reactions was from 2.9 to 4.3. See Ref. 4 for details. 18 3 0.091 0.312 0.709 7.7 25.8 53.6
c
The italic number means the major product should be (R)-13 instead of (S)-13. 19 4 1.501 1.034 0.440 85.3 70.4 35.6
20 5 0.137 0.339 0.661 11.6 27.9 50.7
by L-glutamic acid using methods 1 and 3. The experimental ee 21 5 1 1.428 1.584 0.535 83.6 87.1 42.3
values were 21.4% or 34.8% under an acidic condition. Un- 22 2 0.274 0.298 1.459 22.8 24.7 84.3
23 3 1.878 2.028 0.772 92.0 93.7 57.3
fortunately, the methods 2 and 4 predicted the L-sugar should form
24 4 0.513 0.367 1.359 40.8 30.1 81.7
instead of D-sugar when catalyzed by L-glutamic acid. Method 5 25 5 1.108 0.893 0.873 73.4 63.8 62.8
now predicted close to the experimental results (Table 2, entries 5 a
The italic numbers mean the major product should be (R)-15 instead of the
and 10). This clearly exhibited the head-tail connection with a big expected (S)-15.
ring structure is not available in water. Among all calculation b
The de values of 15 should be the same as the ee values of 10, and therefore, the
methods, method 2 is recommended for further computations in ee values are used here.
relative energy computation.
Similarly, L- or D-type of 4-carbon sugar (10) could form via the Intermediate (S)-15 can decompose into the corresponding four-
corresponding intermediates (3R,20 S)-15 and (3S,20 S)-15 carbon D-sugar, this case is similar to the one that (S)-13 can de-
(Scheme 3). After conformational searches for 15, all conformers compose into the corresponding three-carbon D-sugar. The de

Scheme 3. (left in dash frame) Formation of four-carbon sugar (10) from CHO; (right) L-amino acids used in chiral catalytic formation of 10.

that were recorded by MMFF94S force field were then used in
optimizations at the B3LYP/6-31G(d) level in the gas phase. Then,
the five methods mentioned above were used for optimizations of
all conformers of 15 with relative energy from 0 to 2.5 Kcal/mol.
Again for clarity, (R)-15 and (S)-15 were, respectively, used to rep-
resentative (3R,20 S)-15 and (3S,20 S)-15 in the following discussions.
The quantity differences were then calculated between the lowest
energy conformer of (S)-15 and the lowest energy conformer (R)-
values of 15 should be also equal to the ee values of the four-carbon
D-sugar 10. Thus, as mentioned above, the de values predicted for 15
should equal to the ee of four-carbon D-sugar in the following
discussions.
It is found that the method 2 predicted all the sugar formed
should be D-type catalyzed by the five L-amino acids except for L-4
as a catalyst when Gibbs free energy values were used (entry 17).
More importantly, the most predicted ee values for D type of

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 D. Zhao et al. / Tetrahedron xxx (2016) 1e5 5

4-carbon sugar are bigger than those of 3-carbon sugar using the References and notes
same L amino acid. For a clear comparison, the energy differences
and ee values of 10 catalyzed by L-1 and L-4 are copied, respectively, 1. Cech, T. R. Cell 2009, 136, 599e602.
2. (a) Laiter€a, T.; Lehto, K. Orig. Life. Evol. Biosph. 2009, 39, 545e558; (b) Weber, A.;
to Table 4. The ee values for D-type sugar 10 could reach about 31% Pizzarello, S. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 12713e12717.
predicted by Gibbs free energy, or 88% by zero-point energy cata- 3. (a) Cronin, J.; Pizzarello, S.; Yuen, G. Geochim. Cosmochim. Acta 1985, 49,
lyzed by L-1 (entry 2), or 78% using zero-point energy catalyzed by 2259e2265; (b) Cronin, J.; Pizzarello, S. Science 1997, 275, 951e955; (c) Piz-
zarello, S.; Krishnamurthy, R.; Epstein, S.; Cronin, J. Geochim. Cosmochim. Acta
L-4 if the method 2 has the same reliability as used in the predicted
1991, 55, 905e910; (d) Pizzarello, S.; Weber, A. Science. 2004, 303 1151e1151.
ee values for D-sugar 8. Considering this reality, as two parallel of 4. Breslow, R.; Ramalingam, V.; Appayee, C. Orig. Life Evol. Biosph. 2013, 43,
computations, it could be concluded that method 2 should be more 323e329.
5. (a) Bailey, J.; Chrysostomou, A.; Hough, J.; Gledhill, T.; McCall, A.; Clark, S.;
reliable in the predictions of ee for 13 using the same amino acid. Menard, F.; Tamura, M. Science 1998, 281, 672e674; (b) Bailey, J. Orig. Life Evol.
Biosph. 2001, 31, 167e183; (c) Flores, J.; Bonner, W.; Massey, G. J. Am. Chem. Soc.
Table 4 1977, 99, 3622e3625.
Comparison of the de values predicted for (R)-13 and (S)-13, (R)-15 and (S)-15 using 6. Breslow, R.; Levine, M.; Cheng, Z. Orig. Life Evol. Biosph. 2010, 40, 11e26.
L-1 and L-4, respectively, as the catalysts 7. Levine, M.; Kenesky, C.; Mazori, D.; Breslow, R. Org. Lett. 2008, 10, 2433e2436.
8. (a) Morowitz, H. J. Theor. Biol. 1969, 25, 491e494; (b) Breslow, R.; Levine, M.
Orig. Entry Amino acid Method DE(SeR) of 13 (kcal/mol) Calcd ee (%) for 8a Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 12979e12980; (c) Klussmann, M.; Iwa-
DET DE0 DG DET DE0 DG mura, H.; Mathew, S.; Wells, D.; Pandya, U.; Armstrong, A.; Blackmond, D.
Nature 2006, 441, 621e623; (d) Klussmann, M.; Izumi, T.; White, A.; Arm-
2 1 2 0.132 0.126 0.165 11.1 10.7 13.9 strong, A.; Blackmond, D. J. Am. Chem. Soc. 2007, 129, 7657e7660; (e) Noor-
4 4 0.138 0.153 0.250 11.6 12.9 20.8 duin, W.; Izumi, T.; Millemaggi, A.; Leeman, M.; Meekes, H.; Van Enckevort,
14 4 2 0.178 0.143 d 15.0 12.1 d W.; Kellogg, R.; Kaptein, B.; Vlieg, E.; Blackmond, D. J. Am. Chem. Soc. 2008, 130,
16 4 0.144 0.265 d 12.1 22.1 d 1158e1159.
9. Breslow, R.; Cheng, Z. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 9144e9146.
DE(SeR) of 15 (kcal/mol) Calcd ee (%) for 10a
10. Breslow, R. Tetrahedron Lett. 2011, 52, 2028e2032.
2 1 2 1.9565 1.653 0.389 92.9 88.5 31.7
11. (a) Dixon, D.; Andzelm, J.; Fitzgerald, G.; Wimmer, E.; Jasien, P.; Labanowski, J.;
4 4 1.8850 1.600 0.469 92.1 87.5 37.7 Andzelm, J. Springer: Berlin, 1991, pp 33e56. (b) Wodrich, M. D.; Corminboeuf,
14 4 2 1.7507 1.260 d 90.1 78.8 d C.; Schreiner, P. R.; Fokin, A. A.; Schleyer, P. V. R. Org. Lett. 2007, 9, 1851e1854; (c)
16 4 1.5010 1.034 d 85.3 70.4 d Andzelm, J.; Wimmer, E. J. Chem. Phys. 1992, 96, 1280e1303; (d) Becke, A. D. J.
a Chem. Phys. 1996, 104, 1040e1046.
Intermediate (S)-13 and (S)-15 could decomposed into the corresponding D-
12. (a) Johnson, B. G.; Fisch, M. J. J. Chem. Phys. 1994, 100, 7429e7442; (b) Pople, J.
sugar, thus, their de values should equal to the ee values of the corresponding
A.; Gill, P. M.; Johnson, B. G. Chem. Phys. Lett. 1992, 199, 557e560.
sugars, therefore, the de values of (S)-13 and (S)-15 are regarded as the ee values of 8
13. (a) Johnson, B. G.; Frisch, M. J. Chem. Phys. Lett. 1993, 216, 133e140; (b) Strat-
and 10, respectively. mann, R. E.; Burant, J. C.; Scuseria, G. E.; Frisch, M. J. J. Chem. Phys. 1997, 106,
10175e10183.
4. Summary 14. (a) Tirado-Rives, J.; Jorgensen, W. L. J. Chem. Theo. Comput. 2008, 4, 297e306;
(b) Gill, P. M.; Johnson, B. G.; Pople, J. A.; Frisch, M. J. Chem. Phys. Lett. 1992, 197,
499e505.
This report investigated the ee values of the sugars (8 and 10), 15. (a) Adamo, C.; Barone, V. J. Chem. Phys. 1998, 108, 664e675; (b) Becke, A. D. J.
which derived from the Aldol reaction of Schiff bases formed from Chem. Phys. 1992, 97, 9173e9177.
16. Chai, J. D.; Head-Gordon, M. Phys. Chem. Chem. Phys. 2008, 10, 6615e6620.
2-hydroxyacetaldehyde and 1,3-dihydroxypropan-2-one with five
17. Petersson, G.; Al-Laham, M. A. J. Chem. Phys. 1991, 94, 6081e6090.
L-amino acids, with CHO, respectively. The best method used in 18. (a) Cheeseman, J.; Frisch, M.; Devlin, F.; Stephens, P. Chem. Phys. Lett. 1996, 252,
predictions of ee data of D-sugars is the level of B3LYP/6- 211e220; (b) Allen, W. D.; Yamaguchi, Y.; Cs asz
ar, A. G.; Clabo, D. A.; Reming-
ton, R. B.; Schaefer, H. F. Chem. Phys. 1990, 145, 427e466.
311þþG(2d,p) in water using PCM model based on the experi-
19. (a) Vreven, T.; Mennucci, B.; da Silva, C. O.; Morokuma, K.; Tomasi, J. J. Chem.
mental and theoretical data. Phys. 2001, 115, 62e72; (b) Mennucci, B.; Tomasi, J.; Cammi, R.; Cheeseman, J.;
Frisch, M.; Devlin, F.; Gabriel, S.; Stephens, P. J. Chem. Phys. A 2002, 106,
Acknowledgements 6102e6113.
20. Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113,
6378e6396.
H. J. Zhu thanks the financial supports from Hebei University, 21. (a) Zhu, H. J.; Li, W. X.; Hu, D.-B.; Wen, M. L. Tetrahedron 2014, 70, 8236e8243;
and the High Performance Computer Center of Hebei University. (b) Zhu, H. J.; Jiang, J. X.; Saobo, S.; Pittman, C. U., Jr. J. Org. Chem. 2005, 70,
261e267.

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