Eur. J. Org. Chem. ISSN 1099 0690skkim.skku.edu/abstract/supporting-paper70.pdf · Compound...
Transcript of Eur. J. Org. Chem. ISSN 1099 0690skkim.skku.edu/abstract/supporting-paper70.pdf · Compound...
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Eur. J. Org. Chem. · ISSN 1099–0690
https://doi.org/10.1002/ejoc.201800321
SUPPORTING INFORMATION
Title: Discrimination of the Chirality of α-Amino Acids in ZnII Complexes of DPA-Appended Binaphthyl Imine Author(s): Mukesh Eknath Shirbhate, Raju Nandhakumar,* Youngmee Kim, Sung-Jin Kim, Seong Kyu Kim,* Kwan Mook Kim*
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Experimental Section:
General
Compound R3 was prepared according to the literature procedure1. All other chemicals were commercially available and used without further purifications. The
solvents for dry reactions were dried with appropriate desiccants and distilled prior to use. NMR spectra were recorded on a BrukerAM 300 MHz and 500 MHz
spectrometer in CDCl3 & DMSO-d6 solutions containing tetramethylsilane as internal standard. Chemical shifts are reported in δ unit. Melting points were measured
with Electrothermal IA 9000 digital melting point apparatus and are uncorrected. HRMS spectra were obtained on EI or FAB mode. For column Chromatography silica
gel of 230-400 mesh was used.
References
1. L. Tang, G. Wei, R. Nandhakumar, Z. Guo, Bull. Kor. Chem. Soc. 2011, 32, 3367-3371.
SI-1. Syntheses of (R)-1 and (R)-2
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NO
O
NN
X
O
OH
NOH
O
CHON
N
X
(R)-3(R)-4a (67%) : X = CH
O
O
(R)-5a (81%)
NOH
O
NN
X
(R)-6a (89%)
OH
BrO
O X
O
(R)-1 (73 %)
Conc. HClMnO2, CH2Cl2
K2CO3, CH3CN reflux
K2CO3, CH3CNreflux
EtOH/THFreflux reflux
X
Br Br
X = CH or N
(R)-4b (70%): X = N
N N
N
H
(R)-5b (82%)
(R)-6b (91%)(R)-2 (77%)
R3
Compound binaphtholic acid (400 mg, 1.2 mmol), and 2, 2-dimethoxypropane (0.2 g, 22.24 mmol), were dissolved in dry Acetone (20 ml) and then H2SO4
(only 1 drop) was added in the reaction mixture. The resulting mixture was stirrer room temperature for 12 hours. The resulting mixture was combine with
Na2CO3, and extract with methylene chloride. The organic layer was dried over (NaSO4) and the solvent was concentrated under reduced pressure. The
resulting residue was purified by silica gel column chromatography by using Ethyl acetate / Hexane (1:9) as an eluent to give compound R3. (392 mg, 87%):
mp = 110 oC;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 7.94 (d, 1H, 6Hz), 7.90-7.82 (m, 2H), 7.69 (bs, 1H,), 7.40 -7.27 (m, 3H), 7.27-7.20 (m, 2H), 7.18-7.15 (m,
1H), 7.11-7.01 (m, 1H), 5.25-5.13 (m, 2H), 4.97 (s, 1H), 1.47 (s, 3H), 1.43 (s, 3H).
13C NMR (CDCl3, 70 MHz): δ (ppm): 151.61, 149.06, 134.03, 133.52, 129.97, 129.34, 128.96, 128.26, 128.01, 127.00, 126.44, 125.19, 125.14, 125.04,
124.60, 123.38, 121.60, 117.73, 115.01, 114.60, 100.63, 61.47, 25.54, 24.60.
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R-4a
Compound R-3 (200 mg, 0.56 mmol), was dissolved in dry CH3CN (20 ml) was added in charge K2CO3 (85 mg, 0.61 mmol) at room temperature and allow
the resulting mixture to stirred for 50 min. Then m-Xylylene dibromide (146 mg, 0.56 mmol) was added in the resulting mixture and allow to stirrer at room
temperature for 10 h. After completion of reaction the insoluble materials were removed by filtration, and combined with water and washed with methylene
chloride. The organic layer was dried over (NaSO4) and the solvent was concentrated under reduced pressure. The resulting residue was purified by silica
gel column chromatography by using Ethyl acetate / Hexane (1:4) as an eluent to give compound R-4a. (202 mg, 67%): mp = 80 oC;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 7.99 (d, 1H, 9Hz), 7.95-7.87 (m, 2H), 7.46 (d, 1H, 9Hz), 7.42-7.34 (m, 2H), 7.33-7.26 (m, 3H), 7.24-7.14
(m, 4H), 7.03 (d, 1H, 6Hz), 6.84 (s, 1H), 5.23 (s, 2H), 5.10-5.01 (m, 2H), 4.33-4.25 (m, 2H), 1.44 (s, 3H), 1.40 (s, 3H).
13C NMR (CDCl3, 70 MHz): δ (ppm): 154.46, 148.11, 138.49, 138.01, 134.42, 133.73, 129.86, 129.61, 128.78, 128.77, 128.38, 128.16, 127.86, 127.73,
129.25, 126.96, 126.45, 126.18, 125.91, 125.48, 124.09, 124.01, 123.76, 121.42, 120.71, 118.87, 116.51, 100.23, 71.37, 61.72, 33.69, 25.08, 24.68.
R-4b
Compound R-3 (200 mg, 0.56 mmol), was dissolved in dry CH3CN (20 ml) was added in charge (85 mg, 0.61 mmol) at room temperature and allow the
resulting mixture to stirred for 50 min. Then 2,6 Bis(bromomethyl)pyridine (146 mg, 0.56 mmol) was added in the resulting mixture and allow to stirrer at
room temperature for 10 h. After completion of reaction the insoluble materials were removed by filtration, and combined with water and washed with
methylene chloride. The organic layer was dried over (NaSO4) and the solvent was concentrated under reduced pressure. The resulting residue was purified
by silica gel column chromatography by using Ethyl acetate / Hexane (1:4) as an eluent to give compound R-4b. (211 mg, 70%): mp = 73 oC;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 7.96 (d, 1H, 9Hz), 7.90 (d, 1H, 9Hz), 7.84 (d, 1H, 9Hz), 7.65 (s, 1H), 7.42 (s, 1H), 7.40-7.30 (m, 3H),
7.26-7.12 (m, 5H), 6.82 (d, 1H, 9Hz), 5.23 (s, 2H), 5.20-5.18 (m, 2H), 4.50 (s, 2H), 1.41 (s, 3H), 1.39 (s, 3H).
13C NMR (CDCl3, 70 MHz): δ (ppm): 158.24, 155.94, 154.01, 147.96, 137.67, 134.35, 133.65, 129.70, 129.67, 128.69, 128.12, 127.76, 126.47, 126.12,
125.74, 125.44, 123.99, 123.95, 123.60, 122.10, 121.33, 120.48, 119.90, 118.80, 115.42, 100.16, 71.68, 61.64, 33.94, 25.92, 24.43.
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R-5a
Compound R-4a (390 g, 0.72 mmol), and dipicolylamine (156 mg, 0.75 mmol), were dissolved in dry CH3CN (20 ml) and then K2CO3 (299 mg, 1.44 mmol)
was added in the reaction mixture. The resulting mixture was stirrer at refluxed temperature for 10 h. After completion of reaction the insoluble materials
were removed by filtration, and combined with water and washed with methylene chloride. The organic layer was dried over (NaSO4) and the solvent was
concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography by using Chloroform / Methanol (9:1) as an
eluent to give compound R-5a. (385mg, 81%): mp = 67 oC;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.54 (d, 2H, 6Hz), 7.89-7.79 (m, 3H), 7.62-7.47 (m, 5H), 7.45-7.24 (m, 6H), 7.19-7.11 (m, 5H), 6.97 (d, 2H,
9Hz), 7.22-5.10 (m, 2H), 5.10-5.01 (m, 2H), 3.74 (s, 4H), 3.53 (t, 2H, 8Hz), 1.39 (s, 3H), 1.35 (s, 3H).
13C NMR (CDCl3, 70 MHz): δ (ppm): 159.95, 154.55, 149.14, 147.99, 139.22, 137.87, 136.62, 134.38, 133.65, 129.74, 129.39, 128.67, 128.41, 128.06,
127.79, 127.62, 126.31, 126.06, 125.83, 125.80, 125.43, 123.93, 123.90, 123.59, 123.06, 122.15, 121.28, 120.57, 118.88, 116.73, 71.79, 61.61, 60.15, 58.68,
25.60, 24.72.
R-5b
Compound R-4b (390 g, 0.72 mmol), and dipicolylamine (156 mg, 0.75 mmol), were dissolved in dry CH3CN (20 ml) and then K2CO3 (299 mg, 1.44 mmol)
was added in the reaction mixture. The resulting mixture was then stirrer at refluxed temperature for 10 h. After completion of reaction the insoluble materials
were removed by filtration, and combined with water and washed with methylene chloride. The organic layer was dried over (NaSO4) and the solvent was
concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography by using Chloroform / Methanol (9:1) as an
eluent to give compound R-5b. (389mg, 82%): mp = 65 oC;;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.55-8.53 (m, 2H), 7.91-7.88 (m, 3H), 7.67-7.55 (m, 5H), 7.40-7.30 (m, 5H), 7.26-7.12 (m, 6H), 6.80-6.74 (m,
1H), 5.21 (s, 2H), 5.18-5.12 (m, 2H), 3.88 (s, 4H), 3.85 (s, 2H), 1.40 (s, 3H), 1.37 (s, 3H).
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13C NMR (CDCl3, 70 MHz): δ (ppm): 159.62, 158.66, 157.44, 154.08, 149.32, 147.95, 137.06, 136.63, 134.35, 133.66, 129.59, 129.55, 128.67, 128.08,
127.72, 126.39, 126.05, 125.70, 125.48, 123.90, 123.85, 123.53, 123.18, 122.22, 121.51, 121.31, 119.68, 119.42, 118.88, 115.38, 100.12, 71.80, 61.64, 60.45,
60.38, 25.78, 24.53.
R-6a
Compound R-5a (0.350 g, 0.65 mmol), was dissolved in THF:Et2OH (30:60 ml) and then two drops of HCl was added. The resulting mixture was then
stirred at refluxed for 10 h, at refluxed temperature. The reaction mixture was then combine with brine solution and extract with methylene chloride. The
organic layer was dried over (NaSO4) and the solvent was concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography using Chloroform / Methanol (9:1) as an eluent to give compound R-6a. (291 mg, 89%): mp = 91 oC;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.44-8.42 (m, 2H), 7.97-7.85 (m, 4H), 7.65-7.59 (m, 2H), 7.54 – 7.45 (m, 3H), 7.40-7.29 (m, 5H), 7.23-7.08
(m, 6H), 6.98 (d, 1H, 9Hz), 6.44 (bs, 1H), 5.15 (m, 4H), 3.65 (t, 4H, 15Hz), 3.58 (d, 1H, 12Hz), 3.06(d 1H, 12Hz).
13C NMR (CDCl3, 70 MHz): δ (ppm): 159.95, 154.55, 149.14, 147.99, 139.22, 137.87, 136.26, 134.38, 133.65, 129.74, 129.39, 128.67, 128.41, 128.06,
127.79, 127.62, 126.31, 126.06, 125.83, 125.80, 125.43, 123.93, 123.90, 123.59, 123.06, 122.15, 121.28, 120.57, 118.88, 116.73, 71.23, 62.83, 60.03, 59.05.
R-6b
Compound R-5b (0.350 g, 0.65 mmol), was dissolved in THF:Et2OH (30:60 ml) and then two drops of HCl was added. The resulting mixture was then
stirred at refluxed for 10 h, at refluxed temperature. The reaction mixture was then combine with brine solution and extract with methylene chloride. The
organic layer was dried over (NaSO4) and the solvent was concentrated under reduced pressure. The resulting residue was purified by silica gel column
chromatography using Chloroform / Methanol (9:1) as an eluent to give compound R-6b. (297 mg, 91%): mp = 89 oC;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.46.843 (m, 2H), 7.85.7.81 (m, 3H), 7.76 (d, 1H, 9Hz), 7.59 – 7.53 (m, 2H), 7.46 (t, 1H, 6Hz), 7.39-7.36 (m,
2H), 7.33-7.26 (m, 4H), 7.24-7.16 (m, 3H), 7.14-7.04 (m, 3H), 6.87 (d, 1H, 6Hz), 5.27 (t, 2H, 12Hz), 5.01 (t, 2H, 6Hz), 3.76 (s, 2H), 3.71 (s, 4H).
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13C NMR (CDCl3, 70 MHz): δ (ppm): 159.40, 158.65, 156.26, 154.15, 151.48, 149.11, 137.41, 136.62, 134.29, 133.92, 130.42, 129.87, 129.71, 129.02,
128.24, 128.22, 127.69, 127.14, 126.35, 125.64, 125.22, 124.32, 123.58, 123.28, 122.43, 122.18, 119.71, 118.41, 116.50, 115.50, 70.83, 63.54, 60.17, 59.81.
R-1
To a solution of R-6a (300 g, 0.46 mmol) was dissolved in dry methylene chloride (20 ml) and then MnO2 (25 mmol) was added. The resulting mixture was
then stirred for 10 h, at refluxed temperature. The reaction mixture was filter through the Celite pad and the solvent was concentrated under reduced pressure.
The resulting residue was purified by silica gel column chromatography by using Chloroform / Methanol (9:1) as an eluent to give compound R-1. (218mg,
73%): mp = 79 oC;
1H NMR (CDCl3, 250 MHz) : δ (ppm): 10.54 (bs, 1H), 10.15 (s, 1H), 8.54-8.51 (m, 2H), 8.28 (s, 1H), 7.99 – 7.95 (m, 1H), 7.94 (d, 1H, 9Hz), 7.88(d, 1H,
9Hz), 7.60-7.54(m, 2H), 7.51-7.44(m, 3H), 7.39-7.32(m, 4H), 7.31-7.21(m, 6H), 7.17 – 7.09 (m, 3H), 7.02 (s, 1H), 6.95 (d, 1H, 9Hz), 5.13 (s, 2H), 3.73 (s,
4H), 3.51 (s, 2H).
13C NMR (CDCl3, 70 MHz): δ (ppm): 197.06, 159.91, 154.52, 153.80, 149.14, 139.28, 138.17, 138.10, 137.60, 136.68, 133.97, 130.56, 130.25, 130.07,
129.79, 128.52, 128.47, 128.23, 127.79, 127.611, 126.96, 125.80, 125.66, 125.19, 124.52, 124.20, 123.06, 122.36, 122.21, 118.92, 118.76, 116.09, 71.56,
60.20, 58.74.
MS (ES) m/z (M+H+) HRMS (ES) calcd m/z 615.2522 (C41H34N3O3) found m/z 616.2591.
R-2
To a solution of R-6b (300 g, 0.46 mmol) was dissolved in dry methylene chloride (20 ml) and then MnO2 (25 mmol) was added. The reaction mixture was
then stirred for 10 h, at refluxed temperature. The reaction mixture was filter through the Celite pad and the solvent was concentrated under reduced pressure.
The resulting residue was purified by silica gel column chromatography by using Chloroform / Methanol (9:1) as an eluent to give compound R-2. (229mg,
77%): mp = 72 oC;
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1H NMR (CDCl3, 250 MHz) : δ (ppm): 10.51 (bs, 1H), 10.21 (s, 1H), 8.55-8.52 (m, 2H), 8.32 (s, 1H), 8.00 – 8.97 (m, 1H), 7.96 (d, 1H, 9Hz), 7.88 (d, 1H,
9Hz), 7.66-7.61 (m, 2H), 7.45-7.27 (m, 7H), 7.26.-7.19 (m, 2H), 7.16-7.11 (m, 2H), 6.81 – 6.75 (m, 1H), 5.25 (t, 2H, 12Hz), 3.87 (s, 4H), 3.84 (s, 2H).
13C NMR (CDCl3, 70 MHz): δ (ppm): 196.93, 159.52, 158.74, 157.10, 154.09, 153.77, 149.28, 138.15, 137.94, 137.20, 136.68, 133.90, 130.56, 130.41,
129.99, 129.66, 128.46, 127.79, 127.00, 125.68, 125.09, 124.53, 124.16, 123.20, 122.42, 122.26, 121.68, 119.31, 118.88, 118.08, 115.19, 71.75, 60.36, 60.28.
MS (ES) m/z (M+H+) HRMS (ES) calcd m/z 617.2474 (C40H33N4O3) found m/z 617.2505.
SI-2. General procedure for preparing Zn complexes
In a typical experiment, compound (R)-1 (0.050 g, 0.081 mmol), Zn(ClO4)2•6H2O (0.053 g, 0.178 mmol), racemic phenylalanine (2.0 eq) and KOH (0.045
g, 0.81 mmol) were dissolved in dry MeOH (5 mL). The reaction mixture was then stirred for 8 h, at room temperature. After 8 h stirring, the reaction mixture
was evaporated and extracted with CH2Cl2 and washed with water. TLC for the reaction mixture with an eluent of MeOH/ CH2Cl2 in 2 % indicated the
formation of two products, diastereomers. These two diastereomers (R)-1-Zn-D-Phe and (R)-1-Zn-L-Phe, were successfully separated using column
chromatography on alumina using CH2Cl2:MeOH (9:1) as mobile phase.
(R)-1-Zn-L-Phe
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.45 (d, 1H, 6Hz), 8.00 (d, 1H, 6Hz), 7.82 (s, 1H), 7.69-7.66 (m, 2H), 7.63-7.61 (m, 2H), 7.49 (s, 1H), 7.45 (d, 1H,
9Hz), 7.42-7.25 (m, 4H), 7.25-7.14 (m, 5H), 7.11-7.04 (m, 2H), 7.02-6.97 (m, 3H), 6.92 (d, 1H, 9Hz), 6.82-6.77 (m, 1H), 6.74-6.68 (m, 3H), 6.31 (d, 1H,
9Hz), 5.32 (d, 1H, 12Hz), 5.11 (d, 1H, 15Hz), 4.89 (d, 1H, 15Hz), 4.66 (d, 1H, 18Hz), 4.04-4.00 (m, 1H), 3.79 (d, 1H, 6Hz), 3.74 (d, 1H, 6Hz), 3.57 (d, 1H,
12Hz), 3.51-3.45 (m, 1H), 3.04 (d, 1H, 12Hz), 2.47-2.39 (m, 1H).
(R)-1-Zn-D-Phe
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.40 (d, 1H, 6Hz), 8.15 (d, 1H, 6Hz), 7.99 (s, 1H), 7.67-7.64 (m, 1H), 7.58-7.55 (m, 1H), 7.52-7.41 (s, 1H), 7.40-
7.27 (m, 6H), 7.20-7.08 (m, 7H), 7.04-6.94 (m, 4H), 6.89 (d, 1H, 9Hz), 6.83-6.79 (m, 1H), 6.76-6.65 (m, 3H), 6.51 (d, 1H, 6Hz), 5.44 (d, 1H, 15Hz), 5.27
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(d, 1H, 15Hz), 4.94 (d, 1H, 15Hz), 4.77 (d, 1H, 15Hz), 4.15-4.12 (m, 1H), 3.88 (d, 1H, 15Hz), 3.72 (d, 1H, 15Hz), 3.54-3.50 (m, 1H), 3.44 (d, 1H, 9Hz),
3.03 (d, 1H, 12Hz), 2.32-2.28 (m, 1H).
(R)-1-Zn-L-ala:- By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.80 (s, 1H), 8.44 (d, 1H, 3Hz), 8.07 (d, 1H, 3Hz), 7.99 (s, 1H), 7.82-7.76 (m, 2H), 7.63-7.58 (m, 2H), 7.46 (d, 1H,
9Hz), 7.34-7.31 (m, 1H), 7.19-7.14 (m, 4H), 7.06-6.98 (m, 4H), 6.91-6.90 (m, 1H), 6.85-6.82 (m, 1H), 6.75-6.69 (m, 3H), 6.31 (d, 1H, 6Hz), 5.27 (d, 1H,
12Hz), 5.12 (d, 1H, 18Hz), 4.84 (d, 1H, 12Hz), 4.68 (d, 1H, 15Hz), 3.98-3.95 (m, 1H), 3.80-3.72 (m, 2H), 3.64 (d, 1H, 12Hz), 3.06 (d, 1H, 12Hz), 1.29-1.27
(m, 3H).
(R)-1-Zn-D-ala
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.83 (s, 1H), 8.25-8.22 (m, 2H), 7.99 (s, 2H), 7.81-7.60 (m, 1H), 7.57-7.49 (m, 2H), 7.41 (d, 1H, 9Hz), 7.31-7.22 (m,
3H), 7.19-7.13 (m, 2H), 7.13 (d, 1H, 6Hz), 7.05-6.98 (m, 2H), 6.96-6.85 (m, 3H), 6.74-6.69 (m, 3H), 6.46 (d, 1H, 9Hz), 5.40 (d, 1H, 15Hz), 5.22 (d, 1H,
15Hz), 4.85 (d, 1H, 15Hz), 4.74 (d, 1H, 15Hz), 4.04-3.97 (m, 1H), 3.85 (d, 1H, 15Hz), 3.71 (d, 1H, 12Hz), 3.46 (d, 1H, 9Hz), 3.04 (d, 1H, 12Hz), 1.28-1.27
(m, 3H).
(R)-1-Zn-L-Trp:- By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.33-8.32 (m, 2H), 7.98 (d, 1H, 3Hz), 7.84-7.78 (m, 2H), 7.69-7.67 (m, 4H), 7.45-7.36 (m, 4H), 7.19-7.13 (m, 6H),
7.05-6.96 (m, 4H), 6.88-6.85 (m, 2H), 6.78-6.68 (m, 4H), 6.29 (d, 1H, 6Hz), 5.29 (d, 1H, 18Hz), 5.10 (d, 1H, 18Hz), 4.82 (d, 1H, 18Hz), 4.65 (d, 1H, 18Hz),
4.15-4.12 (m, 1H), 3.76-3.68 (m, 4H), 3.02 (d, 1H, 12Hz), 2.61-2.52 (m, 1H).
(R)-1-Zn-D-Trp
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.31-8.30 (m, 1H), 8.16-8.13 (m, 2H), 7.98 (s, 1H), 7.90 (d, 1H, 6Hz), 7.72 (s, 1H), 7.62-7.37 (m, 6H), 7.32-7.04 (m,
6H), 6.98-6.80 (m, 8H), 6.74-6.63 (m, 3H), 6.48 (d, 1H, 6Hz), 5.43 (d, 1H, 12Hz), 5.25 (d, 1H, 18Hz), 4.89 (d, 1H, 15Hz), 4.76 (d, 1H, 15Hz), 4.26-4.23 (m,
1H), 3.85 (d, 1H, 15Hz), 3.71-3.60 (m, 2H), 3.45 (d, 1H, 9Hz), 3.04 (d, 1H, 12Hz), 2.43-2.38 (m, 1H).
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(R)-1-Zn-L-Val:- By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.72 (s, 1H), 8.44 (d, 1H, 3Hz), 8.05 (d, 1H, 3Hz), 8.01 (s, 1H), 7.83-7.80 (m, 1H), 7.63-7.56 (m, 3H), 7.46-6.43 (m,
2H), 7.25-7.10 (m, 4H), 7.08-7.10 (m, 2H), 6.99-6.88 (m, 3H), 6.83-6.71 (m, 4H), 6.30 (d, 1H, 9Hz), 5.31 (d, 1H, 12Hz), 5.12 (d, 1H, 18Hz), 4.90 (d, 1H,
15Hz), 4.67 (d, 1H, 12Hz), 3.74-3.67 (m, 2H), 3.62 (d, 1H, 3Hz), 3.52 (d, 1H, 12Hz), 3.00 (d, 1H, 12Hz), 1.01 (d, 3H, 6Hz), 0.90-0.83 (m, 1H), 0.72 (d, 3H,
6Hz).
(R)-1-Zn-D-Val
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.73 (s, 1H), 8.36-8.34 (m, 1H), 8.17 (d, 1H, 6Hz), 8.00 (s, 1H), 7.96 (m, 1H), 7.81-7.78 (m, 1H), 7.59-7.56 (m, 1H),
7.51-7.45 (m, 1H), 7.41 (d, 1H, 9Hz), 7.25-7.21 (m, 2H), 7.17-7.13 (m, 2H), 7.09-7.01 (m, 4H), 6.95-6.90 (m, 2H), 6.85-6.76 (m, 2H), 6.73-6.70 (m, 2H),
6.50 (d, 1H, 9Hz), 5.43 (d, 1H, 12Hz), 5.27 (d, 1H, 15Hz), 4.93 (d, 1H, 18Hz), 4.72 (d, 1H, 15Hz), 3.84 (d, 1H, 15Hz), 3.67 (d, 1H, 15Hz), 3.59 (d, 1H,
6Hz), 3.39 (d, 1H, 9Hz), 3.03 (d, 1H, 12Hz), 0.93-0.90 (m, 3H), 0.88-0.83 (m, 1H), 0.77 (d, 3H, 6Hz).
(R)-1-Zn-L-Ser:- By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.89 (s, 1H), 8.41 (d, 1H, 3Hz), 8.09 (d, 1H, 3Hz), 8.01 (s, 1H), 7.80-7.75 (m, 2H), 7.60-7.55 (m, 2H), 7.45 (d, 1H,
9Hz), 7.32-7.28 (m, 1H), 7.21-7.12 (m, 4H), 7.06-6.99 (m, 4H), 6.93-6.84 (m, 2H), 6.78-6.69 (m, 3H), 6.34 (d, 1H, 9Hz), 5.21 (d, 1H, 12Hz), 5.51 (d, 1H,
18Hz), 4.80 (d, 1H, 15Hz), 4.68 (d, 1H, 15Hz), 4.04 (t, 1H, 6Hz), 3.82-3.56 (m, 4H), 3.52 (m, 1H), 3.05 (d, 1H, 9Hz).
(R)-1-Zn-D-Ser
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.91 (s, 1H), 8.38 (d, 1H, 3Hz), 8.25 (d, 1H, 3Hz), 8.06 (s, 2H), 7.82 (d, 1H, 6Hz), 7.60-7.55 (m, 2H), 7.42-7.40 (m,
1H), 7.33-7.28 (m, 1H), 7.21-7.11 (m, 4H), 7.04-7.01 (m, 2H), 6.98-6.87 (m, 4H), 6.74-6.65 (m, 3H), 6.45 (d, 1H, 6Hz), 5.31 (t, 1H, 3Hz), 5.21 (d, 1H,
12Hz), 4.82 (d, 1H, 9Hz), 4.68 (d, 1H, 9Hz), 4.04 (t, 1H, 3Hz), 3.84 (d, 1H, 9Hz), 3.73 (d, 1H, 9Hz), 3.60-3.57 (m, 1H), 3.47-3.44 (m, 2H), 3.04 (d, 1H,
6Hz).
(R)-2-Zn-L-Phe:- By adopting a general procedure mention above.
-
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.54-8.52 (m, 2H), 8.25-8.22 (m, 2H), 7.74-7.69 (m, 2H), 7.58 (s, 2H), 7.35-7.22 (m, 4H), 7.22-7.04 (m, 26H), 7.04-
6.99 (m, 4H), 6.97-6.90 (m, 6H), 6.87-6.84 (m, 2H), 6.68 (d, 2H, 9Hz), 6.61 (d, 2H, 9Hz), 6.22-6.17 (m, 2H), 5.68 (d, 2H, 6Hz), 5.58 (d, 2H, 9Hz), 4.70 (d,
2H, 12Hz), 4.41-4.28 (m, 6H), 4.17 (d, 2H, 15Hz), 3.58-3.52 (m, 2H), 3.14-3.06 (m, 2H), 2.56 (d, 2H, 18Hz), 2.01 (d, 2H, 18Hz).
(R)-2-Zn-L-Trp:- By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.53(d, 2H, 3Hz), 8.28 (d, 2H, 6Hz), 7.89-7.82 (m, 4H), 7.68-7.61 (m, 4H), 7.46-7.41 (m, 2H), 7.28-7.11 (m, 20H),
7.00-6.80 (m, 12H), 6.62-6.60 (m, 4H), 6.50 (d, 2H, 9Hz), 6.08 (t, 2H, 9Hz), 5.72 (d, 2H, 9Hz), 5.56 (d, 2H, 9Hz), 4.74 (d, 2H, 12Hz), 4.36-4.27 (m, 6H),
4.12 (d, 2H, 12Hz), 3.80 (d, 2H, 12Hz), 3.52-3.48 (m, 2H), 3.27-3.24 (m, 2H), 2.48 (d, 2H, 15Hz), 2.07-2.04 (m, 2H), 1.91-1.86 (m, 2H).
(R)-2-Zn-L-Ser:- By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.56-8.54 (m, 2H), 8.25 (d, 2H, 9Hz), 8.19 (d, 2H, 6Hz), 7.84-7.78 (m, 4H), 7.50-7.38 (m, 6H), 7.29-7.16 (m, 16H),
7.05-7.01 (m, 4H), 6.97-6.92 (m, 2H), 6.90 (d, 2H, 9Hz), 6.77 (d, 2H, 9Hz), 6.62 (d, 2H, 9Hz), 6.29 (t, 2H, 9Hz), 5.77 (d, 2H, 9Hz), 5.66 (d, 2H, 9Hz), 4.78
(d, 2H, 12Hz), 4.49-4.30 (m, 6H), 4.17 (d, 2H, 15Hz), 4.02-3.99 (m, 2H), 3.91 (d, 2H, 15Hz), 3.62-3.56 (m, 2H), 2.60 (d, 2H, 15Hz), 2.09-2.04 (m, 2H).
(R)-2-Zn-D-Ser
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.57-8.55 (m, 2H), 8.32 (s, 2H), 8.21 (d, 2H, 9Hz), 8.11-8.08 (m, 2H), 7.85-7.80 (m, 2H), 7.56-7.51 (m, 2H), 7.41 (s,
2H), 7.40-7.33 (m, 8H), 7.22-7.18 (m, 2H), 7.17 (d, 2H, 6Hz), 7.08-6.89 (m, 12H), 6.53 (d, 2H, 9Hz), 6.25 (t, 2H, 6Hz), 5.81 (d, 2H, 6Hz), 5.64 (d, 2H, 6Hz),
4.88 (d, 2H, 12Hz), 4.44-4.30 (m, 4H), 4.30 (d, 2H, 15Hz), 4.41-4.09 (m, 2H), 3.98 (t, 2H, 6Hz), 3.90-3.79 (m, 2H), 3.68 (d, 2H, 15Hz), 2.74 (d, 2H, 15Hz),
2.05 (d, 2H, 15Hz).
(R)-2-Zn-L-Ala:- By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.56 (d, 2H, 3Hz), 8.26 (d, 2H, 9Hz), 8.19 (d, 2H, 3Hz), 7.83-7.79 (m, 4H), 7.49-7.47 (m, 2H), 7.46-7.16 (m, 22H),
7.04 (d, 2H, 9Hz), 6.94 (t, 2H, 9Hz), 6.89 (d, 2H, 9Hz), 6.79 (d, 2H, 9Hz), 6.64 (d, 2H, 9Hz), 6.26 (t, 2H, 6Hz), 5.77 (d, 2H, 9Hz), 5.64 (d, 2H, 9Hz), 4.81
(d, 2H, 12Hz), 4.49-4.34 (m, 2H), 4.24 (d, 2H, 15Hz), 4.02-3.92 (m, 2H), 3.92 (d, 2H, 15Hz), 2.61 (d, 2H, 15Hz), 2.12 (d, 2H, 15Hz), 1.34 (d, 6H, 9Hz).
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(R)-2-Zn-D-Ala
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.56 (d, 2H, 3Hz), 8.18 (d, 2H, 9Hz), 8.12 (d, 2H, 3Hz), 7.94 (m, 2H), 7.81-7.75 (m, 2H), 7.59 (s, 2H), 7.51-7.46 (m,
2H), 7.38-7.33 (m, 2H), 7.28-7.11 (m, 14H), 7.05-6.92 (m, 8H), 6.86-6.81 (m, 4H), 6.60 (d, 2H, 6Hz), 6.21 (t, 2H, 6Hz), 5.76 (d, 2H, 9Hz), 5.73 (d, 2H,
9Hz), 4.80 (d, 2H, 12Hz), 4.45 (d, 2H, 5Hz), 4.37 (m, 2H), 4.25 (d, 2H, 15Hz), 3.80-3.75 (m, 2H), 2.67 (d, 2H, 15Hz), 1.99 (d, 2H, 15Hz), 1.45 (d, 6H, 9Hz).
(R)-2-Zn-L-Met: By adopting a general procedure mention above.
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.55-8.54 (m, 2H), 8.28 (d, 2H, 6Hz), 8.23 (d, 2H, 3Hz), 7.86-7.81 (m, 4H), 7.46-7.37 (m, 5H), 7.33-7.16 (m, 17H),
7.05 (d, 4H, 9Hz), 6.96-6.91 (m, 2H), 6.88 (d, 2H, 9Hz), 6.81 (d, 2H, 9Hz), 6.62 (d, 2H, 9Hz), 6.29-6.24 (m, 2H), 5.74 (d, 2H, 9Hz), 5.61 (d, 2H, 9Hz), 4.76
(d, 2H, 15Hz), 4.50 (d, 2H, 15Hz), 4.39-4.34 (m, 2H), 4.25 (d, 2H, 15Hz), 4.07-4.00 (m, 2H), 3.90 (d, 2H, 15Hz), 2.58 (d, 2H, 15Hz), 2.26-2.21 (m, 4H),
2.08-2.06 (m, 6H), 1.96-1.94 (m, 4H).
(R)-2-Zn-D-Met
1H NMR (CDCl3, 250 MHz) : δ (ppm): 8.56-8.55 (m, 2H), 8.14-8.01 (m, 4H), 7.85-7.75 (m, 2H), 7.58-7.47 (m, 2H), 7.40-7.38 (m, 2H), 7.29-7.26 (m, 4H),
7.20-7.17 (m, 6H), 7.17-7.13 (m, 4H), 7.06-7.05 (m, 4H), 6.98-6.90 (m, 8H), 6.85-6.84 (m, 4H), 6.51 (d, 2H, 3Hz), 6.23 (t, 2H, 6Hz), 5.76-5.74 (m, 4H),
4.89 (d, 2H, 9Hz), 4.47 (d, 2H, 9Hz), 4.42-4.39 (m, 2H), 4.28 (d, 2H, 9Hz), 3.93-3.91 (m, 2H), 3.69 (d, 2H, 9Hz), 2.73-2.71 (m, 2H), 2.40-2.35 (m, 4H),
2.01-2.03 (m, 6H), 1.93-1.83 (m, 4H).
SI-3. Crystallographic data
Table S1. Crystallographic data for (R)-1-L-Ser and (R)-2-L-Phe.
(R)-1-L-Ser (R)-2-L-Phe
Empirical formula C46H40.5ClN4.5O6Zn C98H78N10O8Zn2
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Formula weight 853.15 1654.44
Temperature (K) 296(2) 296(2)
Wavelength (Å ) 0.71073 Å 0.71073 Å
Space group P21 P43212
a(Å ) 12.8655(15) 14.6370(10)
b(Å ) 8.9081(11) 14.6370(10)
c(Å ) 21.613(3) 42.771(3)
α(°) 90.00 90.00
β(°) 95.7534(16) 90.00
γ(°) 90.00 90.00
Volume(Å 3) 2464.5(5) 9163.4(14)
Z 2 4
Density (calc.) (Mg/m3) 1.150 1.199
Absorption coeff.( mm-1) 0.599 0.583
Crystal size (mm) 0.01 x 0.08 x 0.20 0.10 x 0.330 x 0.30
Reflections collected 57551 73241
Independent reflections 8589 [R(int) = 0.1627] 11261 [R(int) = 0.0932]
Data/restraints/parameters 8589 / 58 / 572 11261 / 0 / 473
Goodness-of-fit on F2 0.987 1.038
Final R indices [I>2σ(I)] R1 = 0.0847, wR2 = 0.2081 R1 = 0.1138, wR2 = 0.2922
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SI-4. Energy Calculation
Procedure for calculation.
Starting geometries for optimizing all (R)-1-amino acids were derived from the X-ray crystallography data for (R)-1-L-Ser. The positions of the side
group and the -hydrogen were interchanged to obtain the starting geometry of the (R)-1-D-Ser. For both the L- and D-isomers, the side group were
replaced by H or phenyl to give the starting geometries for the Ala or Phe complexes, respectively. For the Phe or Ser complexes, multiple starting
geometries with varying torsional angles in phenyl ring or hydroxyl moiety were prepared. The starting geometries were then optimized at the B3LYP/6-
31G level of theory. The conformers whose energies are less than 4 kcal/mol higher than the lowest energy conformer were then further optimized at the
B3LYP/6-311G(d) level of theory. Vibrational frequencies were also obtained to calculate the zero-point energy correction and thermodynamic energies.
R indices (all data) R1 = 0.1346, wR2 = 0.2433 R1 = 0.1839, wR2 = 0.3315
Absolute structure parameter - 0.27(4)
Largest diff. peak and hole (e.Å -
3) 1.223 and -0.337 1.213 and -0.619
CCDC number 1549322 1556304
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Starting geometries for optimizing dimeric (R)-2-amino acids were derived from the X-ray crystallography data for (R)-2-L-Phe-L-Phe. The positions of
the side group and the -hydrogen were interchanged to obtain the starting geometries of (R)-2-D-Phe-L-Phe or (R)-2-D-Phe-D-Phe. Multiple starting
geometries with varying the phenyl ring torsion were prepared. Unfortunately, we were not able to obtain optimized structures at the DFT level of theory
since the number of atoms in the dimeric complex is too large. Instead, we report the result from the semi-empirical PM3 calculations.
1. Energies and Geometries
Table S1. a Energies (in kcal/mol) of (R)-1-amino acids calculated at the B3LYP/6-311G(d) level of theory
amino acid
(conformer) L-Ala D-Ala
L-Ser
(A)b
L-Ser
(B)b D-Ser L-Phe
D-Phe
(A)
D-Phe
(B)
Ee 0 1.29 0 4.54 2.83 0 0.79 -0.23
E0 0 1.27 0 4.04 2.88 0 0.69 -0.24
H 0 1.24 0 4.35 2.92 0 0.70 -0.34
G 0 1.01 0 3.71 2.69 0 0.40 0.48
a Ee is the calculated electronic energy, while the zero point energy is included in E0. H and G are the enthalpy and the Gibbs free energy at 1 atm and
298 K. implies that the values are relative to the lowest energy L-isomer. b Conformer B is optimized directly from X-ray crystallography structure.
Conformer B is optimized from a starting geometry with the COH angle in the side group rotated to make intramolecular H-bonding with the carboxylate
group. As the result, conformer B is more stable. (This condition in isolated state may be different from that in the crystalline state.) See Figure S2.
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Figure S1. Optimized geometry of (R)-1-L-Ala (left) and (R)-1-D-Ala (right)
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Figure S2. Optimized geometry of (R)-1-L-
Ser (top left for conformer A and top right
for conformer B) and (R)-1-D-Ser (bottom)
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Figure S3. Optimized geometry of (R)-1-L-
Phe (top) and (R)-1-D-Phe (bottom left for
conformer A and bottom right for conformer
B)
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SI-5. Spectroscopies
-
SI-6. HPLC showing the exclusive formation of (R)-2 with L-forms of Phe and Trp
Complex [(R)-2-Zn-L-Phe]2
The diastereomer was determined by HPLC with an Shiseido Pak-C18 column (5 μm, 4.6 × 250 mm) (H2O/MeOH = 14/86, λ = 280 nm, 1.0
mL/min). [(R)-2-Zn-L-Phe]2 (major diastereomer) = 18.458 min.
-
Complex [(R)-2-Zn-DL-Phe]2
The diastereomer was determined by HPLC with an Shiseido Pak-C18 column (5 μm, 4.6 × 250 mm) (H2O/MeOH = 14/86, λ = 280 nm, 1.0
mL/min). [(R)-2-Zn-DL-Phe]2 (major diastereomer) = 18.409 min., which match with the [(R)-2-Zn-L-Phe]2 (major diastereomer).
-
Complex [(R)-2-Zn-D-Phe]2
The diastereomer was determined by HPLC with an Shiseido Pak-C18 column (5 μm, 4.6 × 250 mm) (H2O/MeOH = 14/86, λ = 280 nm, 1.0
mL/min). [(R)-2-Zn-D-Phe]2 (major diastereomer ) = 1.984 min.
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Complex [(R)-2-Zn-L-Try]2
The diastereomer was determined by HPLC with an Shiseido Pak-C18 column (5 μm, 4.6 × 250 mm) (H2O/MeOH = 14/86, λ = 280 nm, 1.0
mL/min). [(R)-2-Zn-L-Try]2 (major diastereomer) = 9.365 min.
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Complex [(R)-2-Zn-DL-Try]2
The diastereomer was determined by HPLC with an Shiseido Pak-C18 column (5 μm, 4.6 × 250 mm) (H2O/MeOH = 14/86, λ = 280 nm, 1.0
mL/min). [(R)-2-Zn-DL-Try]2 (major diastereomer) = 9.422 min., which match with the [(R)-2-Zn-L-Try]2 (major diastereomer).
-
Complex [(R)-2-Zn-D-Try]2
The diastereomer was determined by HPLC with an Shiseido Pak-C18 column (5 μm, 4.6 × 250 mm) (H2O/MeOH = 14/86, λ = 280 nm, 1.0
mL/min). [(R)-2-Zn-D-Try]2 (major diastereomer) = 1.730 min.