![University of Idaho 454/h… · Web viewe) Scanning UV-vis spectrophotometer 20] A Beer’s law measurement was made at 355 nm on a 9.00 mL sample with analyte X. Its absorbance A,](https://static.fdocument.org/doc/165x107/5fae3fb5115c4a6adf2aafa2/university-of-idaho-454h-web-view-e-scanning-uv-vis-spectrophotometer-20-a.jpg)
Methyl 2,3- di-O-n-octyl-4,6-O-p-methoxybenzylidene … · Web viewE-mail: [email protected];...
34
Supplementary information Lipophilic teicoplanin pseudoaglycon derivatives active against vancomycin and teicoplanin resistant enterococci Zsolt Szűcs, a Ilona Bereczki, a Magdolna Csávás, a Erzsébet Rőth, a Anikó Borbás, a Gyula Batta, b Eszter Ostorházi, c Réka Szatmári, c Pál Herczegh a a Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary, b Department of Organic Chemistry, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary, c Department of Medical Microbiology, Semmelweis University, Mária u. 41, H-1085 Budapest, Hungary * Correspondence: Pál Herczegh, Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, H-4010, Debrecen, Hungary E-mail: [email protected]; Table of contents: Antibacterial study................................. 2 MALDI-TOF spectra of teicoplanin derivatives 1, 2, 4, 5 and 6............................................. 3 Figures and tables for NMR assignment...............8 NMR Spectra........................................ 12 S1
Transcript of Methyl 2,3- di-O-n-octyl-4,6-O-p-methoxybenzylidene … · Web viewE-mail: [email protected];...
Supplementary informationLipophilic teicoplanin pseudoaglycon derivatives active against vancomycin and
teicoplanin resistant enterococci
Zsolt Szűcs,a Ilona Bereczki,a Magdolna Csávás,a Erzsébet Rőth,a Anikó Borbás,a Gyula
Batta,b Eszter Ostorházi,c Réka Szatmári,c Pál Herczegha
aDepartment of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, H-4032
Debrecen, Hungary,bDepartment of Organic Chemistry, University of Debrecen, Egyetem tér 1, H-4032
Debrecen, Hungary,cDepartment of Medical Microbiology, Semmelweis University, Mária u. 41, H-1085
Budapest, Hungary*Correspondence: Pál Herczegh, Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, H-4010, Debrecen, HungaryE-mail: [email protected];
Table of contents:
Antibacterial study................................................................................................2
MALDI-TOF spectra of teicoplanin derivatives 1, 2, 4, 5 and 6..........................3
Figures and tables for NMR assignment...............................................................8
NMR Spectra.......................................................................................................12
References...........................................................................................................24
S1
Antibacterial studyThe antibacterial activity of 1-9 was tested against a panel of Gram-positive bacteria using
broth microdilution method as previously described.1
Table S1. Antibacterial activity of compounds 1-9
Teicoplanin
1 2 3 4 5 6 7 8 9
(MIC, µg/ml)
Bacillus subtilis ATCC 6633
0.5 1.0 1.0 4.0 1.0 2.0 16 0.5 1.0 2.0
Staphylococcus aureus MSSA ATCC 29213
0.5 1.0 4.0 4.0 0.5 0.5 1.0 0.5 0.5 0.5
Staphylococcus aureus MRSA ATCC 33591
0.5 0.5 1.0 4.0 0.5 0.5 1.0 0.5 0.5 0.5
Staphylococcus epidermidis biofilm forming ATCC 35984
4.0 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.156
Enterococcus faecalis ATCC 29212
1.0 0.5 0.5 0.5 2.0 4.0 1.0 0.5 1.0 4.0
Staphylococcus epidermidis mecA
16 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.312
Enterococcus faecalis 15376 VanA
256 0.5 4.0 0.5 1.0 4.0 2.0 1.0 2.0 4.0
Enterococcus faecalis ATCC 51299 VanB
0.5 1.0 4.0 0.5 1.0 4.0 2.0 1.0 1.0 4.0
MIC: Minimum Inhibitory Concentration; ATCC: American Type Culture Collection; MSSA: Methicillin Sensitive Staphylococcus; MRSA: Methicillin Resistant Staphylococcus aureus; mecA: mecA gene expression in Staphylococcu;, vanA +: vanA gene positive; vanB +: vanB gene positive.
S2
MALDI-TOF spectra of teicoplanin derivatives 1, 2, 4, 5 and 6
Compound 1
S3
Compound 2
S4
1726.7800
10001200
14001600
18002000
2200m/z
0
100
200
300
Intens.
Compound 4
S5
Compound 5
S6
Compound 6
S7
1123.95
1165.27
1200.90
1228.28
1258.72
1298.65
1345.331371.42
1408.27
1461.33
1522.08
1581.60
1633.89
1680.41
1780.26
1825.24
1858.45
1893.421914.44
1935.47
1980.39
2075.21
2110.402134.62
2156.53
2202.31
2243.94
2271.47
2424.57
2817.54
12001400
16001800
20002200
24002600
2800m/z
0
500
1000
1500
2000
2500
3000
Intens.
Figures and tables for NMR assignment
Fig. S1. Structure and atom numbering for the NMR assignment of compounds 1, 2, 4, 5, 6.
S8
Fig. S2. Atom numberings of the lipophilic substituents (R in Fig. S1) for the NMR assignment.
S9
Table S2. 2D NMR data for compounds 1 and 2.
Assignment 1 13C 1 1H 2 13C 2 1H
x1 55.9 5.68 56.1 5.65x2 55.0 4.95 55.1 4.94x3 58.4 5.35 58.5 5.35x4 n.d. n.d. 55.3 5.65z6 76.7 5.39 76.7 5.382f 130.7 7.68 130.6 7.663b 110.5 6.36 110.6 6.354b 108.0 5.53 108.0 5.544f 104.9 5.11 104.9 5.115b n.d. n.d. n.d. n.d.6b 128.9 7.88 129.0 7.87GlcNAc 1 99.8 4.40 99.8 4.40
C5 56.4 3.60 56.5 3.60C6 34.4 1.67/1.55 34.5 1.66/1.55C7 40.3 2.41/1.85 40.3 2.42/1.87C8 28.6 1.35 28.7 1.33C9 25.3 1.54 25.4 1.51C10 38.5 3.18/3.13 38.5 3.18/3.13C11 35.0 2.17 35.1 2.15C12 172.5 - 172.3 -C13 - - 38.7 3.01C14 - - 29.3 1.38H3 - - - 7.75
Table S2. (continued) 2D NMR data for compounds 4, 5 and 6.
Assignment 4 13C 4 1H 5 13C 5 1H 6 13C 6 1H
x1 64.3 7.09 64,3 7,05 64.4 7.08x2 55.7 4.86 55,7 4,86 55.7 4.86x3 58.5 5.40 58.5 5,40 58.6 5.40x4 54,9 5,66 54,9 5,66 54.9 5.64z6 75.8 5,36 75.6 5,40 76,0 5,422f 131,9 7,67 131,7 7,67 131,8 7,683b 110.5 6.34 110,5 6,34 110,5 6,334b 108.5 5.55 108,4 5,54 108,4 5,544f 105.0 5.08 104,9 5,07 104.9 5,095b 136.4 7.08 136,4 7,09 136,5 7,116b 129.0 7.87 129.0 7.87 128.9 7.86GlcNAc 1 99.1 4.34 98.8 4,38 99,2 4,39
Triazole 4 144,3 - 144,3 - 142.3 -Triazole 5 124,4 7,73 124,4 7,74 123.2 7,66
S10
α-Glcp 1 97,4 4,74 97,5 4,71 - -α-Glcp 2 80,4 3,15 80,0 3,07 - -α-Glcp 3 81,6 3,39 81,5 3,24 - -α-Glcp 4 77,4 3,29 70,1 3,12 - -α-Glcp 5 70,0 3,54 71,5 3,42 - -MeO-1 54,6 3,26 54,6 3,26 - -
Butyl 2, 2' 19.0 1.32 18.9 1.31 - -Butyl 3, 3' 32.2 1,46 32.1 1.45 - -Butyl 4, 4' 13.9 0,85 14,0 0,86 - -
Phe 2,6 114.0 6,90 - - - -Phe 3,5 129,7 7,22 - - - -Phe 4 131,1 - - - - -Phe 1 159,2 - - - - -Phe 9 (OCH2) 73.9 4.64 / 4.49 - - - -Phe O-Me 55,3 3,72 - - - -
α-Galp 1 - - - - 96.2 5.39
α-Galp 2-5
- - - - 67.7 3.81- - - - 70.0 4.32- - - - 70.6 4.60- - - - 71.4 4.20
α-Galp 6 - - - - 31.7 3.44 / 3.27α-Galp Cq - - - - 108.5/109.0 -
α-Galp CH3- - - - 25.9 1.29- - - - 24.7 1.23
Maleimide 2,5 - - - - 166.0 -Maleimide 3,4 - - - - 136.0 -Maleimide CH2 - - - - 33.6 4.59
TEG a 63,6 4,43 63,6 4,44 - -TEG bulk 69.5-70.4 3.42-3.49 69.5-70.5 3.43-3.51 - -
S11
NMR SpectraMethyl 2,3-di-O-n-butyl-4,6-O-p-methoxybenzylidene-α-D-glucopyranoside (14)
S12
S13
Methyl 2,3-di-O-n-butyl-4-O-p-methoxybenzyl-α-D-glucopyranoside (15)
S14
S15
Methyl 2,3-di-O-n-butyl-4-O-p-methoxybenzyl-6-O-(2,5,8,11,14-pentaoxaheptadec-16-
ynyl)-α-D-glucopyranoside (16)
S16
S17
Methyl 2,3-di-O-n-butyl-6-O-(2,5,8,11,14-pentaoxaheptadec-16-ynyl)-α-D-
glucopyranoside (17)
S18
S19
Compound 1
S20
Compound 2
S21
Compound 4
S22
Compound 5
S23
Compound 6
S24
References1. Sztaricskai, F.; Batta, G., Herczegh, P.; Balázs, A.; Jekő, J.; Rőth, E.; Szabó, P. T.;
Kardos, S.; Rozgonyi, F.; Boda, Z. A new series of glycopeptide antibiotics incorporating a squaric acid moiety. J. Antibiot. 2006, 59, 564-582.
S25
