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S1
Supporting Information
Enantioselective bacterial hydrolysis of amido esters and diamides derived from
()-trans-cyclopropane-1,2-dicarboxylic acid
Katharina G. Hugentobler and Francisca Rebolledo*
Table of Contents:
I. Procedures for the synthesis of racemic compounds implied in the determination of the
enantiomeric excesses:
1. Mixed benzyl methyl trans-cyclopropane-1,2-dicarboxylate (8) (S1)
2. General procedure for the preparation of racemic amido esters (±)-12a-c (S2)
3. General procedure for the preparation of racemic carbamates (±)-14a-c (S3)
4. General procedure for the derivatization of the carboxylic acids with diazomethane (S3)
Scheme I (S3)
II. Chiral HPLC conditions and chromatograms:
1. Biotransformation of methyl (±)-trans-2-carbamoylcyclopropanecarboxylate ((±)-4b) (S4)
2. Biotransformation of benzyl (±)-trans-2-carbamoylcyclopropanecarboxylate ((±)-4c) (S5)
3. Biotransformation of (±)-trans-N-benzylcyclopropane-1,2-dicarboxamide ((±)-10a) (S6)
4. Biotransformation of (±)-trans-N-allylcyclopropane-1,2-dicarboxamide ((±)-10b) (S7)
5. Biotransformation of (±)-trans-N-allyl-N-methylcyclopropane-1,2-dicarboxamide(±)-10c (S8)
6. The Curtius rearrangement of 11a-c: carbamates 14a-c (S9)
III. 1H and
13C NMR spectra for new compounds (S10 to S34)
I. Procedures for the synthesis of racemic compounds implied in the determination of the
enantiomeric excesses
1. Mixed benzyl methyl trans-cyclopropane-1,2-dicarboxylate (8).
The required racemic mixed benzyl methyl ester ()-8 could not be prepared by conventional
methods. A nearly racemic sample was obtained as follows: first, ()-4b (43 mg) was incubated
with a bacterial suspension (A650 = 1.5) in fresh 0.10 M phosphate buffer pH 7.0 (43 mL) and
ethanol (0.43 mL), at 28 ºC during 25 h. The resulting, nearly racemic, product 6b (ee = 8%, 37 mg,
0.26 mmol) was converted into the acid chloride as described for its analogue (±)-6a in the first step
corresponding to the synthesis of (±)-9a-c. Then, the crude acid chloride was dissolved in
anhydrous THF (2.0 mL) and treated with benzyl alcohol (53 L, 0.51 mmol) and triethylamine (72
mL, 0.51 mmol) at room temperature. After 12 h, aqueous 1 M HCl was added and the mixture
extracted with AcOEt. Evaporation of organic solvents and purification of the residue by flash
chromatography (n-hexane/ethyl acetate 15:1 as the eluent) yielded product 8 (ee = 8% chiral-
HPLC analysis) as a colourless liquid. H (300.13 MHz, CDCl3)7.43-7.30 (5 H, m, Ph), AB system
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S2
centered to 5.13 ppm (|JA,B| = 12.5 Hz, 2H, CH2-Ph,), 3.70 (3 H, s, OMe), 2.38-2.17 (2 H, m, 2 x
CH), 1.52-1.40 (m, 2H, CH2); C (75.5 MHz, CDC13)172.0 (C=O), 171.5 (C=O), 135.4 (C), 128.5
(CH), 128.3 (CH), 128.2 (CH), 66.8 (CH2), 55.1 (CH3), 22.3 (CH), 22.2 (CH), 15.4 (CH2). MS
(ESI+) m/z 257.0 ((M+Na)+, 100%).
2. General procedure for the preparation of racemic amido esters (±)-12a-c.
A mixture of dimethyl (±)-trans-cyclopropane-1,2-dicarboxylate ((±)-3b) (0.16 g, 1.0 mmol) and
the corresponding amine (1.0 mmol) was heated in a sealed tube nearly to the boiling point of the
amine during 20 h (for 12a) or 60 h (for 12b,c). Then aqueous 1 M HCl (5 mL) and CH2Cl2 (8 mL)
were added. The organic phase was separated and the aqueous layer again extracted with CH2Cl2.
The organic phases were combined and washed with brine. Evaporation of solvents and subsequent
flash column chromatography of the residue (n-hexane/ethyl acetate 2:1 as the eluent) yielded the
corresponding amido esters (±)-12a-c.
(1) Methyl ()-trans-2-(N-benzylcarbamoyl)cyclopropanecarboxylate (()-12a). White solid
(0.12 g, 50%); mp 104-105 ºC; H (300.13 MHz, CDC13) 7.40-7.25 (5 H, m, Ph), 6.14 (1 H, br s,
NH), 4.44 (2 H, d, J = 5.7 Hz, CH2Ph), 3.67 (3 H, s, OCH3), 2.21 (1 H, ddd, J1 = 9.2 Hz, J2 = 5.5
Hz, J3 = 3.7 Hz, CH), 1.94 (1 H, ddd, , J1 = 8.9 Hz, J2 = 5.4 Hz, J3 = 3.7 Hz, CH), 1.49 (1 H, ddd,
J1 = 9.1 Hz, J2 = 5.5 Hz, J3 = 3.6 Hz, CHH), 1.33 (1 H, ddd, J1 = 9.1 Hz, J2 = 5.5 Hz, J3 = 3.6 Hz,
CHH); C (75.5 MHz, CDC13) 173.1 (C=O), 169.9 (C=O), 137.9 (C), 128.7 (CH), 127.8 (CH),
127.6 (CH), 52.0 (CH3), 44.0 (CH2), 24.2 (CH), 21.3 (CH), 14.8 (CH2); MS (ESI+) m/z 256.0
((M+Na)+, 100%).
(2) Methyl ()-trans-2-(N-allylcarbamoyl)cyclopropanecarboxylate (()-12b). White solid (62
mg, 34%); mp 86-87 ºC; H (300.13 MHz, CDC13) 5.84 [2 H, ddt (Jtrans = 17.2 Hz (d), Jcis = 10.2
Hz (d), J = 5.7 Hz (t), CH=CH2) overlapped with br s (NH)], 5.24-5.12 (2 H, m, CH=CH2), 3.90 (2
H, tt, J1 = 5.8 Hz, J2 = 1.5 Hz, NCH2), 3.69 (3 H, s, OCH3), 2.18 (1 H, ddd, J1 = 8.8 Hz, J2 = 5.7
Hz, J3 = 3.8 Hz, CH), 1.94 (1 H, ddd, J1 = 8.6 Hz, J2 = 5.8 Hz, J3 = 3.8 Hz, CH), 1.47 (1 H, ddd, J1
= 8.8 Hz, J2 = 5.8 Hz, J3 = 3.8 Hz, CHH), 1.33 (1 H, ddd, , J1 = 8.7 Hz, J2 = 5.7 Hz, J3 = 3.8 Hz,
CHH); C (75.5 MHz, CDC13) 173.1 (C=O), 169.8 (C=O), 133.8 (CH), 116.7 (CH2), 52.0 (CH3),
42.3 (CH2), 24.3 (CH), 21.3 (CH), 14.7 (CH2); MS (ESI+) m/z 389.1 ((2M+Na)+, 100%; (M+H)
+,
85%).
(3) Methyl ()-trans-2-(N-allyl-N-methylcarbamoyl)cyclopropanecarboxylate (()-12c).
Colorless oil (20 mg, 10%); H (300.13 MHz, CDC13) corresponding to a 47:53 mixture of
rotamers: 5.90-5.61 (1 H, m, CH=CH2), 5.32-5.05 (2 H, m, CH=CH2), 4.17-3.94 (2 H, m, NCH2),
3.70 and 3.68 (2 H, two s, OCH3), 3.09 (3 H for minor rotamer, s, NCH3), 2.94 (3 H for major
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S3
rotamer, s, NCH3), 2.40-2.10 (2 H, m, 2 x CH), 1.50-1.12 (2 H, m, CH2); C (75.5 MHz, CDC13)
corresponding to a mixture of rotamers: 173.3, 173.2, 170.3, 169.8, 132.7, 132.4, 117.4, 116.7,
52.2, 52.0, 50.4, 34.7, 34.2, 21.7, 21.1, 21.0, 15.4, 15.3; MS (ESI+) m/z 220.0 ((M+Na)+, 100%).
3. General procedure for the preparation of racemic carbamates (±)-14a-c
Racemic carbamates (±)-14a-c were obtained from the corresponding racemic carboxylic acid (±)-
11a-c as described for the optically active samples. In turn, racemic carboxylic acids (±)-11a-c were
prepared as follows: the racemic ethyl amido ester (±)-9a-c (0.50 mmol) was dissolved in ethanol
(0.50 mL) and then aqueous 1 M NaOH (0.50 mL) was added. The mixture was heated at 80 ºC
during 2 h. After this time, ethanol was removed, water (5 mL) and aqueous 1 M NaOH (0.2 mL)
were added, and the mixture extracted with CH2Cl2. The organic phase was discarded. The aqueous
phase was acidified with conc. HCl and extracted with ethyl acetate (2 × 10 mL). The combined
organic phases were washed with brine and dried with Na2SO4. Evaporation of solvents yielded the
corresponding racemic carboxylic acid. Spectroscopic data for (±)-11a-c matched those of the
optically active samples.
(±)-11a: Yield, 95%; mp 172-173 ºC.
(±)-11b: Yield, 90%; mp 152-153 ºC.
(±)-11c: Yield, 91%; mp 73-75 ºC.
4. General procedure for the derivatization of the carboxylic acids with diazomethane.
An excess of a solution of diazomethane in a mixture of diethyl ether/methanol (40 mM) was added
to a sample of 1.0 mg of the corresponding carboxylic acid. After 2-3 min. solvents were
evaporated and the resulting methyl ester was analysed by chiral GC or HPLC. The optically active
carboxylic acids (isolated from the enzymatic reactions) and the methyl esters derivatives are
collected in Scheme I.
Scheme I. Methyl esters derivatives
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S4
II. Chiral HPLC conditions and chromatograms:
1. Biotransformation of methyl (±)-trans-2-carbamoylcyclopropanecarboxylate ((±)-4b) (Table
1 of the manuscript, entry 4)
Remaining substrate (1R,2R)-4b was isolated with ee > 99%.
HPLC conditions: Chiralcel OD; hexane/propan-2-ol 90:10, 0.8 mL/min, 210 nm, 20 C; tR = 13.8
(1R,2R) and 15.9 (1S,2S) min; RS = 2.1.
(±)-4b (1R,2R)-4b with ee > 99%
Product (1S,2S)-6b was isolated with ee = 91%. It was transformed into (1S,2S)-3b (Scheme I)
GC conditions for (±)-3b: RTBetaDEXse chiral column, heating at 50 ºC during 5 min, and then, a
ramp of 1 ºC/min; tR = 56.8 (1R,2R) and 58.2 (1S,2S) min; RS = 2.9.
(±)-3b (1S,2S)-3b with ee = 91%
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S5
2. Biotransformation of benzyl (±)-trans-2-carbamoylcyclopropanecarboxylate ((±)-4c):
Remaining substrate (1R,2R)-4c was isolated with ee = 65%.
HPLC conditions: Chiralpak IA; n-hexane/propan-2-ol 93:7, 0.8 mL/min, 20 C, 215 nm; tR = 20.4
(1S,2S) and 23.1 (1R,2R) min; RS = 2.2.
(±)-4c (1R,2R)-4b with ee > 99%
Product (1S,2S)-6c was isolated with ee = 94%. For the chiral-HPLC analysis, 6c was transformed
into 8 (Scheme I).
HPLC conditions: Chiralpak IA; n-hexane/propan-2-ol 98:2, 0.8 mL/min, 20 C, 215 nm; tR = 9.2
(1R,2R) and 9.8 (1S,2S) min; RS = 1.3.
Nearly racemic 8 (ee = 8%) (1S,2S)-8 with ee = 94%
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S6
3. Biotransformation of (±)-trans-N-benzylcyclopropane-1,2-dicarboxamide ((±)-10a) (Table 2
of the manuscript, entry 1):
Remaining substrate (1R,2R)-10a was isolated with ee = 75%.
HPLC conditions: Chiralpak IA; n-hexane/propan-2-ol 95:5, 0.8 mL/min, 20 C, 215 nm; tR = 29.7
(1S,2S) and 34.5 (1R,2R) min; RS = 1.4.
(±)-10a (1R,2R)-10a with ee = 75%
Product (1S,2S)-11a was isolated with ee = 95%. For the chiral-HPLC analysis, 11a was
transformed into 12a (Scheme I).
HPLC conditions: Chiralpak IA; n-hexane/propan-2-ol 93:7, 0.8 mL/min, 20 C, 215 nm; tR = 17.0
(1S,2S) and 18.7 (1R,2R) min; RS = 2.1.
(±)-12a (1S,2S)-12a with ee = 95%
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S7
4. Biotransformation of (±)-trans-N-allylcyclopropane-1,2-dicarboxamide ((±)-10b) (Table 2
of the manuscript, entry 2):
Remaining substrate (1R,2R)-10b was isolated with ee = 93%.
HPLC conditions: Chiralcel OD; n-hexane/propan-2-ol 94:6, 0.8 mL/min, 30 C, 215 nm; tR = 13.1
(1R,2R) and 14.8 (1S,2S) min; RS = 1.2.
(±)-10b (1R,2R)-10b with ee = 93%
Product (1S,2S)-11b was isolated with ee = 92%. For the chiral-HPLC analysis, 11b was
transformed into 12b (Scheme I).
HPLC conditions: Chiralcel OD; n-hexane/propan-2-ol 97:3, 0.8 mL/min, 20 C, 210 nm; tR = 25.9
(1R,2R) and 29.2 (1S,2S) min; RS = 1.7.
(±)-12b (1S,2S)-12b with ee = 92%
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S8
5. Biotransformation of (±)-trans-N-allyl-N-methylcyclopropane-1,2-dicarboxamide ((±)-10c)
(Table 2 of the manuscript, entry 3):
Remaining substrate (1R,2R)-10c was isolated with ee = 97%.
HPLC conditions: Chiralpak IA; n-hexane/propan-2-ol 95:5, 0.8 mL/min, 20 C, 215 nm; tR = 32.6
(1S,2S) and 36.7 (1R,2R) min; RS = 1.3.
(±)-10c (1R,2R)-10c with ee = 97%
Product (1S,2S)-11c was isolated with ee = 99%. For the chiral-HPLC analysis, 11c was
transformed into 12c (Scheme I).
HPLC conditions: Chiralcel OD; n-hexane/propan-2-ol 95:5, 0.8 mL/min, 20 C, 215 nm; tR = 11.5
(1R,2R) and 14.1 (1S,2S) min; RS = 3.5.
(±)-12c (1S,2S)-12c with ee = 99%
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S9
6. The Curtius rearrangement of 11a-c: carbamates 14a-c
14a. HPLC conditions: Chiralcel OD; n-hexane/propan-2-ol 80:20, 0.8 mL/min, 20 C, 215 nm; tR
= 15.3 (1S,2S) and 17.8 (1R,2R) min; RS = 1.7.
(±)-14a (1S,2S)-14a with ee = 95%
14b. HPLC conditions: Chiralcel OD; n-hexane/propan-2-ol 80:20, 0.8 mL/min, 20 C, 210 nm; tR
= 10.1 (1S,2S) and 12.1 (1R,2R) min; RS = 2.3.
(±)-14b (1S,2S)-14b with ee = 92%
14c. HPLC conditions: Chiralcel OD; n-hexane/propan-2-ol 85:15, 0.8 mL/min, 20 C, 215 nm; tR =
17.3 (1S,2S) and 21.1 (1R,2R) min; RS = 2.5.
(±)-14c (1S,2S)-14c with ee = 99%
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S10
1H and
13C NMR spectra of 4b in CDCl3:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S11
1H and
13C NMR spectra of 4c in CDCl3:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S12
1H and
13C NMR spectra of 6c in CD3OD:
4.6
89
1
2.0
00
0
1.8
93
0
2.0
22
7
Inte
gra
l
7.3
54
6
5.1
79
45.1
37
85.1
35
25.0
93
6
3.3
10
0
(ppm)
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0
R-234-crA h1_wsopt MeOD {C:\Bruker\bacs} Bruker 2
17
4.9
256
17
3.1
148
13
7.3
138
12
9.5
960
12
9.3
328
12
9.2
889
67
.89
36
49
.00
00
23
.04
27
22
.99
49
15
.71
18
(ppm)
2030405060708090100110120130140150160170
R-234-crA c13_swopt MeOD 18-07-11
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S13
1H and
13C NMR spectra of 8 in CDCl3:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S14
1H and
13C NMR spectra of 9a in CDCl3:
5.0
33
2
0.9
70
3
2.0
00
0
2.0
33
7
0.9
97
2
1.1
32
6
1.0
21
7
4.0
63
7
Inte
gra
l
6.6
07
7
4.4
01
04.3
82
7
4.0
37
74.0
13
9
1.2
39
01.2
15
21.1
91
4
(ppm)
1.01.52.02.53.03.54.04.55.05.56.06.57.07.5
R-255-A h1_wsopt CDCl3 1-03-2013
17
2.8
073
17
0.0
132
13
7.9
156
12
8.5
433
12
7.7
500
12
7.4
060
76
.95
00
60
.85
91
43
.78
54
23
.98
77
21
.30
59
14
.70
66
14
.00
46
(ppm)
0102030405060708090100110120130140150160170180
R-255-A c13.220 CDCl3 1-03-2013
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S15
1H and
13C NMR spectra of 9b in CDCl3:
1.8
59
7
1.9
77
1
2.0
87
1
2.0
00
0
0.9
99
6
0.9
73
8
0.9
67
9
4.1
37
6
Inte
gra
l
5.9
01
25.8
82
35.8
67
75.8
63
45.8
48
25.8
44
55.8
29
35.8
25
05.8
10
45.8
06
15.7
90
95.7
72
0
4.1
71
84.1
48
04.1
24
24.1
00
43.9
20
03.9
15
13.9
09
63.9
00
53.8
95
63.8
90
73.8
81
63.8
76
13.8
71
2
2.1
96
02.1
83
22.1
77
12.1
66
82.1
64
32.1
54
02.1
47
92.1
35
1
1.2
88
41.2
64
61.2
40
8
(ppm)
1.01.52.02.53.03.54.04.55.05.56.06.57.0
R-Id-B AmidoÚster Et/NAlil h1_wsopt CDCl3 15-02-13
1.8
59
7
1.9
77
1
5.9
01
25.8
82
35.8
67
75.8
63
45.8
48
25.8
44
55.8
29
35.8
25
05.8
10
45.8
06
15.7
90
9
5.7
72
0
5.2
38
65.2
33
15.2
28
25.2
23
3
5.1
81
35.1
75
85.1
71
55.1
67
25.1
63
05.1
58
15.1
38
05.1
33
15.1
28
85.1
24
0
(ppm)
5.005.105.205.305.405.505.605.705.805.906.00
R-Id-B AmidoÚster Et/NAlil Ampliaci¾n CDCl3 15-02-13
1.8
59
7
1.9
77
1
5.9
01
25.8
82
35.8
67
75.8
63
45.8
48
25.8
44
55.8
29
35.8
25
05.8
10
45.8
06
15.7
90
9
5.7
72
0
5.2
38
65.2
33
15.2
28
25.2
23
3
5.1
81
35.1
75
85.1
71
55.1
67
25.1
63
05.1
58
15.1
38
05.1
33
15.1
28
85.1
24
0
(ppm)
5.005.105.205.305.405.505.605.705.805.906.00
R-Id-B AmidoÚster Et/NAlil Ampliaci¾n CDCl3 15-02-13
0.9
99
6
0.9
73
8
0.9
67
9
4.1
37
6
Inte
gra
l
2.1
96
02.1
83
22.1
77
12.1
66
82.1
64
32.1
54
02.1
47
92.1
35
1
1.9
64
41.9
51
61.9
44
91.9
35
11.9
32
11.9
22
31.9
16
21.9
03
4
1.4
88
91.4
76
11.4
69
41.4
59
61.4
57
21.4
46
81.4
40
11.4
27
9
1.3
51
71.3
38
91.3
32
91.3
22
51.3
20
01.3
10
31.3
03
6
(ppm)
1.301.401.501.601.701.801.902.002.102.202.30
R-Id-B AmidoÚster Et/NAlil Ampliaci¾n CDCl3 15-02-13
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S16
1H and
13C NMR spectra of 9c in CDCl3:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S17
1H and
13C NMR spectra of 10a (in CD3OD and DMSO-d6, respectively):
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S18
1H and
13C NMR spectra of 10b in CD3OD:
0.8
95
9
2.0
00
0
2.3
01
7
2.0
94
5
2.5
19
2
Inte
gra
l5.8
43
65.8
29
95.8
25
25.8
07
85.7
91
05.7
73
1
5.2
15
75.2
10
55.1
58
45.1
53
15.1
23
65.1
18
45.0
89
45.0
84
2
3.8
20
03.8
14
73.8
09
53.8
01
63.7
96
33.7
91
0
3.3
10
0
(ppm)
1.21.62.02.42.83.23.64.04.44.85.25.66.0
R-225-crB
0.8
95
9
5.9
01
05.8
82
65.8
64
75.8
48
35.8
43
65.8
29
95.8
25
25.8
07
85.7
91
05.7
73
1
(ppm)
5.805.90
2.0
00
0
5.2
15
75.2
10
5
5.1
58
45.1
53
15.1
23
65.1
18
45.0
89
45.0
84
2
(ppm)
5.10
2.3
01
7
3.8
20
03.8
14
73.8
09
53.8
01
63.7
96
33.7
91
0
(ppm)
3.803.85
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S19
1H and
13C NMR spectra of 10c in CD3OD:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S20
1H and
13C NMR spectra of 11a in CD3OD:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S21
1H and
13C NMR spectra of 11b in CD3OD:
0.3
67
2
0.9
02
5
1.7
04
2
2.0
00
0
1.9
83
8
2.3
85
1
8.4
66
2
5.8
52
05.8
29
45.7
95
25.2
19
45.2
14
25.1
62
05.1
56
85.1
29
95.1
25
25.0
95
75.0
91
0
3.8
32
63.8
20
53.8
15
23.8
08
43.8
02
13.7
96
83.3
10
0
(ppm)
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
R-225-crA2 h1_wsopt MeOD 13-07-11
17
5.8
173
17
2.7
585
13
5.3
394
11
6.3
208
49
.00
00
43
.00
61
24
.49
40
21
.94
17
14
.65
96
(ppm)
2030405060708090100110120130140150160170
R-225-crA2 c13_swopt MeOD 14-07-11
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S22
1H and
13C NMR spectra of 11c in CD3OD:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S23
1H and
13C NMR spectra of (±)-12a in CDCl3.
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S24
1H and
13C NMR spectra of (±)-12b in CDCl3.
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S25
1H and
13C NMR spectra of (±)-12c in CDCl3.
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S26
1H NMR spectrum of the crude acyl azide (1S,2S)-13a in CDCl3.
The molar ratio 13a:12a is 96:4.
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S27
1H NMR spectrum of the crude acyl azide (1S,2S)-13b in CDCl3.
The molar ratio 13b:12b is 96:4.
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S28
1H NMR spectrum of the crude acyl azide (1S,2S)-13c in CDCl3.
The molar ratio 13c:12c is 93:7.
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S29
1H-NMR,
13C-NMR, and HSQC spectra of 14a in DMSO-d6:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S30
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S31
1H-NMR,
13C-NMR, and HSQC spectra of 14b in CDCl3:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S32
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S33
1H-NMR,
13C-NMR, and HSQC spectra of 14c in CDCl3:
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013
S34
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2013