Cesario and Miller
JOCNote
1
(
dec); HNMR(600MHz, DMSO-d )δ1.21 (ddd, 1H, J=13.8 Hz,
(()-(S*)-3-Amino-3-((1R*,2R*,3S*,4R*)-4-(2,4-dioxo-3,4-
dihydropyrimidin-1(2H)-yl)-2,3-dihydroxycyclopentyl)propanoic
Acid 2a and (()-(S*)-3-Amino-3-((1R*,2S*,3R*,4R*)-4-(2,4-di-
oxo-3,4-dihydropyrimidin-1(2H)-yl)-2,3-dihydroxycyclopentyl)
propanoic Acid 2b. A water solution (0.36 mL) of a 1:8 ratio
of 1a:1b (10 mg, 0.036 mmol) was treated with 2 M NaOH
(0.089 mL, 0.18 mmol) and was stirred for 18 h at rt. The reaction
mixture was adjusted to pH 7 with 1 M HCl. The neutralized
reaction mixture was concentrated to solids under reduced pressure.
The crude material was adsorbed on Sephadex LH20 and eluted
with MeOH to afford a 1:6 ratio of 2a:2b as white solids (10.6 mg,
94%). Compound 2a: H NMR (600 MHz, D O) δ 1.67-1.72 (m,
1H), 2.22-2.29 (m, 2H), 2.50 (dd, 1H, J=17.5 Hz, 9.5 Hz),
2.75 (dd, 1H, J=17.5 Hz, 4.0 Hz), 3.58 (ddd, 1H, J=9.2 Hz,
8.6 Hz, 3.4 Hz), 3.91-3.94 (m, 1H), 4.06-4.08 (m, 1H), 4.56-4.62
(m, 1H), 5.86 (d, 1H, J=8.0 Hz), 7.67 (d, 1H, J=8.0 Hz);
6
6
2
5
.8 Hz, 6.8 Hz), 2.50-2.56(m, 2H), 2.85(dd, 1H, J=5.0 Hz, 2.1 Hz),
.86-2.90 (m, 1H), 3.57 (ddd, 1H, J=8.5 Hz, 2.6 Hz, 2.6 Hz), 5.46-
.50 (m, 1H), 5.57 (d, 1H, J=8.2 Hz), 5.78 (ddd, 1H, J=5.6 Hz, 2.1
Hz, 2.1 Hz), 6.01 (ddd, 1H, J=5.6 Hz, 2.1 Hz, 2.1 Hz), 7.42 (d, 1H,
13
J=7.9 Hz), 7.97 (s, 1H), 11.27 (s, 1H); C NMR (150 MHz, DMSO-
6
d ) δ 32.2, 40.9, 48.4, 48.8, 60.8, 101.6, 131.0, 137.1, 141.7, 150.9,
-
1
163.3, 167.0; IR (thin film, cm ) 1749, 1689, 1614, 1461; HRMS
+
+
(
FAB) m/z [M+H] : calcd for C12
48.1026.
()-1-((1R*,2S*,3R*,4R*)-2,3-Dihydroxy-4-((S*)-4-oxoaze-
tidin-2-yl)cyclopentyl)pyrimidine-2,4(1H,3H)-dione 1a and 1-
(1R*,2R*,3S*,4R*)-2,3-dihydroxy-4-((S*)-4-oxoazetidin-2-yl)
cyclopentyl)pyrimidine-2,4(1H,3H)-dione 1b. A t-BuOH:H
14 3 3
H N O , 248.1035; found,
2
(
1
2
(
2
O
solution (9:1, 1.8 mL: 0.2 mL) of 8 (50 mg, 0.20 mmol) and
N-methylmorpholine N-oxide (47 mg, 0.40 mol) was treated
with a 2.5% (w/w) solution of osmium tetraoxide in t-BuOH
1
3
C NMR (125 MHz, D O) δ 27.0, 37.0, 40.3, 45.3, 51.5, 70.5,
2
+
72.8, 102.0, 144.5, 152.5, 166.5, 177.9; HRMS (ESI) m/z[M + H] :
(
0.40 mL, 0.04 mmol) and the heterogeneous reaction mixture
was stirred at rt for 18 h. After 18 h, the clear yellow reaction
mixture was treated with solid Na (576 mg, 3.03 mmol)
+
calcd for C H N O , 300.1196; found, 300.1190. HRMS (ESI)
18
1
2
3 6
+
m/z [M + Na] : calcd for C12
2
S
2
O
5
17 3
H N NaO
6
, 322.1015; found,
O) δ 1.97 (ddd,
1
322.1010. Compound 2b: H NMR (600 MHz, D
and the mixture was stirred at rt for 30 min. The clear solution
was filtered through a Whatman Glass Microfiber Filter (Type
GF/F) to remove the brown precipitate. The clear filtrate was
concentrated to solids under reduced pressure, toluene (3 mL)
was added, and the solution was concentrated to solids. The
solids were triturated with MeOH (3ꢀ5 mL) and the wet solids
were dried under vacuum to afford a 1:8 ratio of 1a:1b as white
2
1H, J=12.6 Hz, 12.6, Hz, 10.0 Hz), 2.21-2.26 (m, 1H), 2.33 (ddd,
1H, J=12.6 Hz, 8.2 Hz, 7.0 Hz), 2.50 (dd, 1H, J=16.7 Hz, 8.5 Hz),
2.66 (dd, 1H, J=16.4 Hz, 4.7 Hz), 3.72 (ddd, 1H, J=10.8 Hz, 7.3
Hz, 4.7 Hz), 4.29-4.32 (m, 2H), 5.08 (ddd, 1H, J=10.0 Hz, 8.2 Hz,
1
3
8.2 Hz), 5.84 (d, 1H, J=7.9 Hz), 7.92 (d, 1H, J=7.9 Hz); C NMR
(150 MHz, D O) δ 29.0, 38.6, 40.7, 49.2, 54.8, 70.9, 71.6, 100.9,
146.0, 156.9, 166.3, 178.1; HRMS (ESI) m/z [M+H] : calcd for
2
1
+
solids (45 mg, 80%). H NMR of the crude reaction mixture indi-
cated a 1:3 ratio of 1a:1b. Compound 1a: H NMR (600 MHz, D O)
1
+
2
C
12
H
18
N
3
O
6
, 300.1196; found, 300.1190. HRMS (ESI) m/z [M+
Na] : calcd for C H N NaO , 322.1015; found, 322.1010.
+
δ 1.61 (ddd, 1H, J=12.3 Hz, 12.3 Hz, 9.1 Hz), 2.19-2.28 (m, 2H),
.73 (dd, 1H, J=15.2 Hz, 2.4 Hz), 3.11 (dd, 1H, J=15.3 Hz, 4.7 Hz),
.87 (ddd, 1H, J=6.8 Hz, 4.7 Hz, 2.1 Hz), 3.94 (dd, 1H, J=6.2 Hz,
.7 Hz), 4.24-4.27 (m, 1H), 4.63-4.68 (m, 1H), 5.86 (d, 1H, J=7.9
12
17
3
6
2
3
4
Acknowledgment. We thank Dr. Jed Fisher for helpful
discussions, Dr. Bill Boggess and Nonka Sevova for mass
spectroscopic analyses and Dr. Jaroslav Zajicek for NMR
assistance. We acknowledge The University of Notre Dame
and NIH (GM068012) for support of this work.
13
Hz), 7.66 (d, 1H, J=7.9 Hz); C NMR (150 MHz, D O) δ 26.0,
40.1, 45.9, 49.6, 55.4, 71.2, 73.4, 101.9, 144.4, 152.3, 166.3, 171.9;
HRMS (FAB) m/z [M+H] : calcd for C12
2
+
+
5
H
16
3
N O
, 282.1090;
1
found, 282.1081. Compound 1b: H NMR (600 MHz, D O) δ
2
1
2
5
.95-2.01 (m, 1H), 2.19-2.26 (m, 2H), 2.76 (dd, 1H, J=15.2 Hz,
.3 Hz), 3.13 (dd, 1H, J=15.3 Hz, 4.7 Hz), 3.98 (ddd, 1H, J=6.5 Hz,
.0 Hz, 2.4 Hz), 4.24-4.27(m, 1H), 4.29(dd, 1H, J=7.3 Hz, 4.4 Hz),
.99-5.04 (m, 1H), 5.82 (d, 1H, J=8.2 Hz), 7.90 (d, 1H, J=7.9 Hz);
3
Supporting Information Available: General methods and
C
1
13
4
experimental details for the preparation of 9-12. H and
1
C NMR (150 MHz, D
2
O) δ 28.5, 40.8, 42.4, 48.1, 55.4, 71.2, 72.1,
NMR spectra for compounds 1a-b, 2a-b, 5, 7, 8, 10, 11 and 12.
This material is available free of charge via the Internet at http://
pubs.acs.org.
+
00.6, 146.1, 152.7, 166.3, 171.9; HRMS (FAB) m/z [M+H] : calcd
1
+
16 3 5
for C12H N O , 282.1090; found, 282.1081.
J. Org. Chem. Vol. 74, No. 15, 2009 5733