1574
J Chem Crystallogr (2011) 41:1573–1578
O
O
heated to 40 °C with stirring for 24 h. After completion of
the reaction, 20 mL of water was added and the mixture was
extracted with 3 9 25 mL of chloroform which was washed
with equal volumes of 0.1 N HCl and saturated NaHCO3,
then dried over Na2SO4. The crude extract was purified
by silica column chromatography and applying a solvent
gradient beginning with hexane, proceeding through 5%
methanol over ethyl acetate. An overall 97% yield of product
H
H
H
H
N
N
O
HO
HN
NH
NH2
N
H
H2N
H
OH
OH
Streptolidine
2
Fig. 1 Structures of the amino acid streptolidine, a constituent of
natural peptide antibiotics, and the amino-oxazoline lactam analog 2
1
5 was obtained after purification. 5: H NMR (500 MHz,
CDCl3) d 7.55 (d, 1H), 7.28 (5H), 7.24 (d, 1H), 7.09 (t, 1H),
7.03 (t, 1H), 6.88 (s, 1H), 6.66 (broad, 1H), 5.12 (t, 1H), 5.01
(d, 1H), 4.66 (m, 1H), 3.99 (s, 1H), 3.77 (s, 1H), 3.72 (s, 1H),
3.38 (m, 2H), 3.18 (m, 1H), 0.94 (s, 9H), 0.1 (d, 6H); 13C
NMR (500 MHz, CDCl3) d 168.4, 166.2, 156.4, 156.2,
136.7, 136.2, 128.7, 128.3, 124.1, 121.9, 119.5, 118.8, 111.6,
109.9, 79.6, 66.9, 62.5, 58.9, 50.1, 38.8, 27.9, 25.9, 18.2,
-4.6; MS exact mass calculated for C31H39N5O6Si 605.27,
found 606.27 (M ? H)?.
NH
O
O
H
N
HN
+
NH2
HO
NH
O
Cbz
H
O
TBDMS
3
4
HATU, HOAt
Et3N
NH
O
O
O
H
H
(3S,4S,5R)-3-(((S)-4-((1H-Indol-3-yl)Methyl)-5-Oxo-
4,5-Dihydro-1H-Imidazol-2-yl)Amino)-4-((Tert-
Butyldimethylsilyl)Oxy)-5-Hydroxypiperidin-2-One (1)
N
O
HN
Si
NH
O
NH
O
Compound 5 (240 mg, 0.4 mmol) was dissolved in
anhydrous methanol (7 mL) to 0.06 M. 8–12 mol.% Pd
of 10% (wt) activated palladium on carbon (24 mg) was
added to an oven-dried two-necked round-bottom flask.
The flask was purged twice with argon, followed by
addition of the 5 solution via a syringe. The flask was
then thoroughly purged with hydrogen gas and stirring
was started. The progress of the reaction was monitored
via TLC (10% methanol in ethyl acetate). After 24 h the
reaction mixture was vacuum filtered through Celite
followed by washing with methanol. The collected fil-
trate was condensed. A mixture of compounds 6 and 1
was purified via normal phase silica gel column chro-
matography and by applying a solvent gradient starting
with hexanes and proceeding through 15% methanol in
ethyl acetate. The mixture of compounds 6 and 1 was
dissolved in methanol and added slowly to a solution of
two equivalents of potassium fluoride in methanol, on
ice, with stirring. After 1 h, the ice bath was removed
and the reaction mixture was allowed to reach room
temperature. After standing overnight a white precipitate
had formed. Filtration through a sintered funnel and
drying gave the precipitated product 1 as a white solid in
65% yield. 1: 1H NMR (500 MHz, DMSO) d 10.9 (s,
1H), 7.9 (s, 1H), 7.58 (t, 1H), 7.48 (t, 1H), 7.33 (td, 1H),
7.20 (dd, 1H), 7.03 (t, 1H), 6.93 (t, 1H), 5.52 (s, 1H,
NH), 5.08 (s, 1H), 4.03 (s, 1H), 3.98 (dd, 1H), 3.91 (d,
1H), 3.2 (dd, 1H), 3.10 (dt, 1H), 3.0 (m, 1H), 2.85 (s,
1H), 2.68 (s, 1H), 2.54 (d, 1H), 0.8 (s, 9H), 0.06 (d, 3H),
-0.05 (d, 3H).
5
H2, Pd[C]
MeOH
NH
O
O
O
H
H
N
O
HN
Si
NH
NH2
6
O
H
N
H
N
O
HN
N
NH
O
OH Si
1
Fig. 2 Synthesis of the title compound 1
coupling reagents HATU and HOAt (2 eq each), triethyl-
amine (5 eq). Z-Trp-OH (0.62 mmol, 211 mg) was dis-
solved in 3.7 mL DMF in a dried flask. To the solution
was added HATU (0.83 mmol, 170 mg, 2 eq) and HOAt
(112 mg, 0.83 mmol, 2 eq) and Triethylamine (5 eq,
2.05 mmol, 275 lL). Then 3 (0.41 mmol, 118 mg) dis-
solved in 5 mL DMF was added. The reaction mixture was
123
Dutta, Sanjay
