Design, synthesis, and antibacterial evaluation of novel derivatives of NPS-2143 for the treatment of. . .
epichlorhydrin (6.55 mmol) in acetic acid (10 ml) was
heated to 75 °C. After 2 h, the reaction mixture was cooled
to room temperature. The resulting mixture was con-
centrated under vacuum and the product was extracted with
AcOEt (3 × 100 ml). The AcOEt extract was dried
(Na2SO4), filtered and evaporated in vacuo. The crude was
purified on the silica gel to afford compound 46a or 46b.
The solution of compound 46a (0.83 mmol) or 46b (0.83
mmol) and KF (2.49 mmol) in acetonitrile (10 ml) was
refluxed for 3 h. Then the resulting mixture was filtered and
the filtrate was concentrated under vacuum, the product was
purified on the silica gel to afford epoxides 47a or 47b.
A mixture of epoxide 47a (0.29 mmol) or 47b (0.29
(3 × 10 ml). The AcOEt extract was dried (Na2SO4), filtered
and evaporated in vacuo. The crude product was purified on
the silica gel to afford compound 35.
Microbiology
In vitro anti-MRSA activity
Bacteria strains MRSA ATCC 33591, MRSA ATCC
43300, MSSA ATCC 25923, MSSA ATCC 6538, MSSA
ATCC 25913, and E. coli ATCC 25922 were purchased
from the American Type Culture Collection. All synthe-
sized compounds were tested for their in vitro antibacterial
activity against MRSA, MSSA, and E. coli by performing a
microdilution (MIC). Methicillin-resistant Staphylococcus
aureus (MRSA and MSSA) was cultured in
Mueller–Hinton broth (MH, Oxoid, Basingstoke, England)
at 37 °C under aerobic conditions. MICs of NPS-2143
analogs used against MRSA were determined in triplicate
using flat-bottom 96-well microtiter plates (TPP, Trasadin-
gen, Switzerland).
mmol),
2-methyl-1-(naphthalen-2-yl)propan-2-amine
hydrochloride (0.43 mmol), and triethylamine (0.43 mmol)
in 15 ml of ethanol was refluxed for 7 h (TLC-monitoring).
After cooling, the solvent was removed in vacuo. The crude
product was purified on a silica gel column to give pure
compounds 48 or 49.
General procedure for the synthesis of compounds 33–35,
50
Acknowledgements The authors acknowledge National Natural Sci-
ence Foundation of China (No.81473253) for financial support.
A mixture of 31 (0.073 mmol), 1,1′-carbonyldiimidazole
(CDI) (0.183 mmol) and trimethylamine (0.073 mmol) in
10 ml of dichloromethane was stirred at room temperature
for 5 h (TLC-monitoring). Then the solvent was removed in
vacuo. The crude product was purified on a silica gel col-
umn to give pure compound 33.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Publisher’s note: Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
A mixture of 31 (0.145 mmol) or compound 48 (0.145
mmol), iodomethane (0.290 mmol), and NaOH in 10 ml of
methanol was stirred at room temperature for 3 h (TLC-
monitoring). Then the solvent was removed in vacuo. The
crude product was purified on a silica gel column to give
pure compounds 34 and 50.
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To a solution of compound 32 (0.30 mmol) and NaOH
(0.90 mmol) in H2O (4 ml) and 1,4-dioxane (4 ml) was added
di-tert-butyl dicarbonate (Boc2O) (0.90 mmol). The mixture
was stirred at room temperature for 1 h (TLC-monitoring).
Then the resulting mixture was extracted with AcOEt (3 × 10
ml). The AcOEt extract was dried (Na2SO4), filtered and
evaporated in vacuo. The crude was purified on the silica gel
to afford N-Boc intermediate. The intermediate was treated
with NaH (2.40 mmol) and iodomethane (3.40 mmol) in
DMF (3 ml), after stirring for 3 h (TLC-monitoring) at room
temperature. Then the resulting mixture was extracted with
AcOEt (3 × 10 ml). The AcOEt extract was dried with
Na2SO4, filtered and evaporated in vacuo. The crude was
purified on the silica gel to afford another N-protected
methoxy intermediate. Then this intermediate was treated
with hydrochloric acid in ethanol (10 ml). After stirring for 1
h at room temperature, the resulting mixture was concentrated
under vacuum and the product was extracted with AcOEt