Synthesis and Total 1H- and 13C-NMR Assignment of Cephem Derivatives for Use in ADEPT Approaches
Abstract
:Introduction
Results and Discussion
Synthesis
NMR Assignments
Position | δ 13C (ppm) | δ 1H (ppm); (int., mult.); J (Hz) | gHMBC |
---|---|---|---|
2 | 45.4 | a – 4.08; (1H, d); J=18.6 | C3; C4; C6 |
b – 3.71; (1H, d); J=18.6 | |||
3 | 120.1 | --- | --- |
4 | 125.3 | --- | --- |
6 | 66.6 | 4.99; (1H, d); J=4.5 | C8 |
7 | 58.2 | 5.98; (1H, dd); J=8.3; J=4.5 | C6; C8; C10 |
8 | 164.5 | --- | --- |
9 | --- | 8.47; (1H, d); J=8.3 | C7; C8; C10 |
10 | 170.2 | --- | --- |
11 | 35.7 | a – 3.92; (1H, d); J=15.5 | C10; C12; C13 |
b – 3.83; (1H, d); J=15.5 | |||
12 | 136.7 | --- | --- |
13 | 126.9 | 7.29; (1H, d); J=5.5 | --- |
14 | 126.7 | 7.28; (1H, dd); J=6.7; J=5.5 | --- |
15 | 125.1 | 7.54; (1H, d); J=6.7 | --- |
1’ | 67.4 | a – 5.30 ; (1H, d); J=13,0 | C2; C3; C4; C2’ |
b – 4.91; (1H, d); J=13,0 | |||
2’ | 151.5 | --- | --- |
3’ | 155.1 | --- | --- |
4’ | 122.4 | 7.52; (2H, d); J=9.0 | C3’; C5’; C6’ |
5’ | 125.4 | 8.31; (2H, d); J=9.0 | C3’; C5’; C6’ |
6’ | 145.2 | --- | --- |
1” | 159.7 | --- | --- |
2” | 79.3 | 6.96; (1H, s) | C1’’; C3’’; C4’’ |
3” | 139.6 | --- | --- |
4” | 126.6 | a – 7.44; (2H, d); J=7.4 | C2’’ |
b – 6.98; (2H, d); J=3.5 | |||
5” | 128.5 | 7.34; (4H, dd); J=7.4; J=6.7 | C3’’; C6’’ |
6” | 128.4 | 7.38; (2H, dd); J=6.7; J=3.5 | --- |
Position | δ 1H (ppm), (int., mult.), J (Hz) | δ 13C (ppm) | gHSQC | gHMBC |
---|---|---|---|---|
2 | a – 3.62; (1H, d); J=18.8 | 45.6 | C2 | C3; C4; C6; C1’ |
b – 2.94; (1H, d); J=18.8 | ||||
3 | --- | 123.4 | --- | --- |
4 | --- | 124.6 | --- | --- |
6 | 4.17 – 4.26; (1H, m) | 66.7 | C6 | C8 |
7 | 5.81 – 5.96; (1H, m) | 59.0 | C7 | C6; C8; C10 |
8 | --- | 164.5 | --- | --- |
9 | 6.99; (1H, d); J=9.8 | --- | --- | C7; C10 |
10 | --- | 170.5 | --- | --- |
11 | 3.72; (2H, s) | 37.2 | C11 | C10; C11; C12 |
12 | --- | 135.0 | --- | --- |
13 14 | 6.83 – 6.92; (2H, m) | 127.2 127.4 | C13; C14 | C12; C15 |
15 | 7.08 – 7.40; (1H, m) | 125.9 | C15 | --- |
1’ | a – 5.05; (1H, d); J=14.3 | 63.4 | C1’ | C2; C3; C4; C2’ |
b – 4.52; (1H, d); J=14.3 | ||||
2’ | --- | 156.0 | --- | --- |
4’ | 2.99 – 3.13; (2H, m) | 41.2 | C4’ | --- |
5’, 6’ | 1.38 – 1.66; (4H, m) | 26.6; 33.9 | --- | C4’; C5’; C6’; C7’; C8’ |
7’ | 3.43 – 3.55; (1H, m) | 47.9 | --- | C5’; C6’ |
8’ | 1.18; (3H, d); J=6.0 | 20.6 | C8’ | C6’; C7’ |
10’ | --- | 144.9 | --- | --- |
11’ | 6.25; (1H, brs) | 92.0 | C11’ | C12’; C13’; C19’ |
12’ | --- | 159.6 | --- | --- |
13’ | 6.19; (1H, brs) | 97.1 | C13’ | C11’; C12’; C19’ |
14’ | --- | 130.1 | --- | --- |
15’ | 7.83; (1H, d); J=8.1 | 135.1 | --- | --- |
16’ | 7.07 – 7.41; (1H, m) | 122.1 | --- | --- |
17’ | 8.43; (1H, dd); J=5.8; J=1.6 | 144.4 | C17’ | C16’; C19’ |
19’ | --- | 135.3 | --- | --- |
20’ | 3.79; (3H, s) | 55.5 | C20’ | C12’; C20’ |
1’’ | --- | 160.1 | --- | --- |
2’’ | 6.81; (1H, s) | 80.4 | C2’’ | C1’’; C3’’; C4’’a; C4’’b |
3’’ | --- | 139.2 | --- | --- |
4’’a, 4’’b 5’’, 6’’ | 7.08 – 7.40; (10H, m) | 127.7; 127.8 128.6; 128.8; 128.3; 128.4 | --- | --- |
Position | δ 1H (ppm); (int., mult.); J (Hz) | δ 13C (ppm) | gCOSY | gHSQC | gHMBC |
---|---|---|---|---|---|
2 | 3.75 – 3.94; (2H, m) | 45.2 | --- | C2 | C3; C4; C6 |
3 | --- | 119.7 | --- | --- | --- |
4 | --- | 125.3 | --- | --- | --- |
6 | 4.88; (1H, d); J=4.8 | 66.2 | H7 | C6 | C8 |
7 | 5.80; (1H, dd); J=8.4; J=4.8 | 58.0 | H6; H9 | C7 | C6; C8; C10 |
8 | --- | 164.1 | --- | --- | --- |
9 | 8.42; (1H, d); J=8.4 | --- | H7 | --- | C7; C8; C10 |
10 | --- | 170.0 | --- | --- | --- |
11 | 3.75 – 3.94; (2H, m) | 35.6 | --- | C11 | C10; C12; C13 |
12 | --- | 136.8 | --- | --- | --- |
13; 14 | 6.91 –6.97; (2H, m) | 126.4; 126.7 | H15 | C13; C14 | C12; C15 |
15 | 7.36; (1H, dd); J=4.8; J=1.8 | 125.1 | H13; H14 | C15 | C12; C13 |
1’ | a – 5.11; (1H, d); J=13.1 b – 4.52; (1H, d); J=13.1 | 62.7 | H1’a; H1’b | C1’ | C2; C3; C4; C2’ |
2’ | --- | 155.8 | --- | --- | --- |
3’ | 7.29; (1H, t); J=5.9 | --- | H4’ | --- | --- |
4’ | 2.98; (2H, d); J=5.9 | 40.3 | H3’; H5’; H6’ | C4’ | --- |
5’; 6’ | 1.41 – 1.70; (4H, m) | 26.1; 33.2 | H4’; H7’ | C5’; C6’ | C8’ |
7’ | 3.55 – 3.66; (1H, m) | 47.0 | H8’ | C7’ | --- |
8’ | 1.19; (3H, d); J=6.3 | 20.1 | H7’ | C8’ | C6’; C7’ |
10’ | --- | 144.5 | --- | --- | --- |
11’ | 6.48; (1H, d); J=2.6 | 91.7 | H13’ | C11’ | C12’; C13’; C15’ |
12’ | --- | 159.0 | --- | --- | --- |
13’ | 6.25; (1H, d); J=2.6 | 96.3 | H11’ | C13’ | C12’; C15’ |
14’ | --- | 129.6 | --- | --- | --- |
15’ | 8.08; (1H, dd); J=8.4; J=1.5 | 135.0 | H16’ | C15’ | C11’; C15’; C17’ |
16’ | 7.43; (1H, dd); J=8.4; J=4.2 | 122.1 | H15’; H17’ | C16’ | C14’; C17’ |
17’ | 8.53; (1H, dd); J=4.2; J=1.5 | 144.1 | H16’ | C17’ | C15’; C16’ |
19’ | --- | 134.3 | --- | --- | --- |
20’ | 3.75 – 3.94; (3H, m) | 55.0 | --- | C20’ | C12’; C20’ |
1’’ | --- | 162.0 | --- | --- | --- |
Conclusions
Experimental
General
NMR Experiments
Synthesis
Cephalothin derivative 5
Diphenyldiazomethane
3-Hydroxymethyl-8-oxo-7-[(2-thienylacetyl)-amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (2a)
3-Hydroxymethyl-8-oxo-7-[(2-thienylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic aciddiphenylmethyl ester (3)
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4’’-nitrophenoxy)carbonyl]oxy]methyl]-8-oxo-7-[(2-thienylacetyl)amino]-diphenylmethyl ester and 5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic acid-3-[[[(4’’-nitrophenoxy)carbonyl]oxy]methyl]-8-oxo-7-[(2-thienylacetyl)amino]- diphenylmethyl ester (4)
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4’’-nitrophenoxy)carbonyl]oxy]methyl]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (5)
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino)-pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (6)
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 3-[methyl 4-(6-methoxyquinolin-8-ylamino)-pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]- 5-dioxide (7)
Acknowledgements
References
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- Sample Availability: No compound samples are available.
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Blau, L.; Menegon, R.F.; Ferreira, E.I.; Ferreira, A.G.; Boffo, E.F.; Tavares, L.A.; Heleno, V.C.G.; Chung, M.-C. Synthesis and Total 1H- and 13C-NMR Assignment of Cephem Derivatives for Use in ADEPT Approaches. Molecules 2008, 13, 841-854. https://doi.org/10.3390/molecules13040841
Blau L, Menegon RF, Ferreira EI, Ferreira AG, Boffo EF, Tavares LA, Heleno VCG, Chung M-C. Synthesis and Total 1H- and 13C-NMR Assignment of Cephem Derivatives for Use in ADEPT Approaches. Molecules. 2008; 13(4):841-854. https://doi.org/10.3390/molecules13040841
Chicago/Turabian StyleBlau, Lorena, Renato Farina Menegon, Elizabeth Igne Ferreira, Antonio Gilberto Ferreira, Elisangela Fabiana Boffo, Leila Aley Tavares, Vladimir Constantino Gomes Heleno, and Man-Chin Chung. 2008. "Synthesis and Total 1H- and 13C-NMR Assignment of Cephem Derivatives for Use in ADEPT Approaches" Molecules 13, no. 4: 841-854. https://doi.org/10.3390/molecules13040841