Supporting Information
© Wiley-VCH 2006
69451 Weinheim, Germany
Regiocontrol in Manganese(III)-Mediated Oxidative Heterobicyclizations: New Access to
the Core Skeletons of Oroidin Dimers
Xianghui Tan and Chuo Chen*
Structure Assignments. The structures of 7, 9, 10, 13, 15, 18, 21, 24, 25, 26 and 28 were determined
by NMR experiments (gCOSY, NOESY, gHMQC). The structure of 15 was further supported by X-ray
analysis (CCDC 290044). Oxidative rearrangement of 7 provided 15 (Scheme S1). No coupling
between H9 and H10 (ageliferin numbering) was observed by 1H NMR in 7, 9 and 10, suggesting a
dihedral angle of 90° between H9 and H10.
These data strongly favors the trans-C9-C10 relative
configuration as serious distortion would arise from the corresponding cis configuration. All the NOE
data are consistent with the structures of 9 and 10 as shown in Figure S1. TIPS-deprotection of 9 and 10
followed by Dess-Martin oxidation afforded two compounds identical by TLC and 1H NMR (Scheme
S2). These two compounds bears the same magnitude of optical rotation however opposite direction
([α]D –132° for 29; [α]D +131° for 30, i.e. 30 = ent-29).
Scheme S1
O
BnN
mCPBA, CH2Cl2
H
O
Me
O
O
BnN
10
BocHN O
O
23 °C, 7 d
96% yield
7
BnN
O
H
H
Me
O
O
15
O
Cl
NBn
H
O
Bn
N O
O
NBn
H
H
BnN
OTIPS
10
O
9
O
9
Cl
NBn
H
H
OTIPS
9
BocHN O
O
10
Figure S1. Summary of the NOE data of 9 and 10 on the equilibrium geometries (MMFF/PM3) with
constrain of H9-C9-C10-H10 dihedral angel to 90° (t-Bu, i-Pr and Ph groups removed for clarity)
Scheme S2
O
BnN
Cl
NBn
H
10
O
H
O
BocHN O
9
O
BnN
OTIPS
9
Cl
NBn
H
10
O
BocHN O
H
OTIPS
9
O 10
O
1. NH4F, HOAc, MeOH
60 °C, 12 h, 83% yield
2. Dess-Martin periodinane
CH2Cl2, 45 °C, 3 h
99% yield
BnN
Cl
NBn
H
H
O
BocHN O
O
29
O
1. NH4F, HOAc, MeOH
60 °C, 48 h, 81% yield
2. Dess-Martin periodinane
CH2Cl2, 45 °C, 3 h
96% yield
O
BnN
Cl
NBn
H
H
O
O
BocHN O
O
30 (ent-29)
General Procedures. All reactions with air and moisture-sensitive materials were performed in flamedried glassware under a positive pressure of argon. Flash column chromatography was performed as
described by Still et al. (Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923–2925)
employing E. Merck silica gel 60 (230–400 mesh ASTM) Davisil silica gel (Grade 633, 200–425 mesh);
or using a HPFC Biotage system (Biotage, Inc.) with pre-packed FLASH silica gel. TLC analyses were
performed on 250 μm Silica Gel 60 F254 plates purchased from EM Science and visualized by quenching
of UV fluorescence (λmax=254 nm) or by staining with ceric ammonium molybdate or potassium
permanganate.
Materials. Commercial solvents and reagents were used as received with the following exceptions:
anhydrous tetrahydrofuran and methylene chloride, Hünig’s base and 2,6-lutidine were distilled from
calcium hydride under nitrogen. Dess-Martin reagent was prepared according to literature references
(Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 5437–5438; Ireland, R. E.; Liu, L. J.
Org. Chem. 1993, 58, 2899.)
O
BnN
1,3-Dibenzyl-4-formylimidazolidin-2-one (31). To a solution of imidazole (2.04 g, 30
NBn
mmol, 1.0 equiv) in N,N-dimethylformamide (100 mL) was added sodium hyride (0.79 g,
CHO
33 mmol, 1.1 equiv) and benzyl bromide (7.13 mL, 60 mmol, 2.0 equiv). This solution was
stirred at 23 °C for 2 h before copper(II) chloride (4.03 g, 30 mmol, 1.0 equiv) and sodium hydride (1.44
g, 60 mmol, 2.0 equiv) were added. The reaction was warmed to 80 °C and oxygen was bubbled
through the reaction for 12 h. The reaction was then cooled to 0 °C and phosphorus oxychloride (6.9
mL, 75 mmol, 2.5 equiv) was added slowly. The reaction was stirred at 0 °C for 30 min and then 23 °C
for 2 h. The solvent was removed by vacuum and the residue was dissolved by dichloromethane (500
mL). Water (100 mL) followed by saturated sodium bicarbonate solution was added until no bubbles
generated.
The layers were separated and the organic layer was washed with 10% ammonium
hydroxide/saturated ammonium chloride (1:1, 50 mL×5) followed by brine (50mL), dried over
anhydrous sodium sulfate, filtered and concentrated to give pure 31 (8.40 g, 99%) as yellow oil: Rf =
0.40 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3090, 3032, 1713, 1660, 1651, 1453, 1164, 739,
700; 1H NMR (400 MHz, CDCl3) δ 9.16 (s, 1H), 7.45-7.20 (m, 10H), 6.91 (s, 1H), 5.24 (s, 2H), 4.88 (s,
2H); 13C NMR (75 MHz, CDCl3) δ 177.0, 153.6, 137.7, 135.5, 129.3, 128.9, 128.7, 128.4, 127.9, 127.8,
123.3, 48.1, 46.2; HRMS(ES+) calcd for C18H17N2O2 (M+H)+ 293.1290, found 293.1276.
S2
(E)-Cinnamyl
OH O
O
BnN
NBn
3-(2,4-dibenzylimidazolidin-3-onyl)-3-
hydroxypropionate (32). To a solution of cinnamyl acetate (361 mg,
2.05 mmol, 1.2 equiv) in tetrahydrofuran (20 mL) cooled at –78 °C was
O
added a solution of lithium hexamethyldisilazide (1.0 M in hexanes, 2.56 mL, 2.56 mmol, 1.5 equiv).
The solution was stirred for 30 min before a solution of aldehyde 31 (500 mg, 1.71 mmol, 1.0 equiv) in
tetrahydrofuran (2 mL) was added. After stirring for additional 30 min, the reaction was quenched with
saturated aqueous sodium bicarbonate solution (2 mL). The solvent was removed and the residue was
dissolved with methylene chloride (50 mL), washed with brine (10 mL), dried over anhydrous sodium
sulfate, filtered, concentrated to afford the crude alcohol which can be used without purification. The
crude product could be purified by silica gel (Davisil 633) column chromatography to afford pure 32
(605 mg, 76%) as pale yellow oil: Rf = 0.26 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3325, 2926,
1733, 1667, 1451, 1162, 965, 733, 696; 1H NMR (400 MHz, CDCl3) δ 7.36-7.20 (m, 15H), 6.60 (d, J =
16.0 Hz, 1H), 6.18 (dt, J = 15.8, 6.6 Hz, 1H), 6.02 (s, 1H), 5.16 (d, J = 5.8 Hz, 1H), 4.96 (d, J = 5.8 Hz,
1H), 4.79 (s, 2H), 4.76 (dd, J = 8.3, 4.1 Hz, 1H), 4.70 (d, J = 8.4 Hz, 2H), 2.70-2.55 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 171.7, 154.1, 137.9, 136.9, 136.1, 135.1, 129.1, 129.0, 128.9, 128.6, 128.2, 128.1,
127.8, 127.4, 126.9, 123.8, 122.5, 107.6, 65.9, 61.8, 47.4, 45.3, 38.9; HRMS(ES+) calcd for C29H29N2O4
(M+H)+ 469.2127, found 469.2109.
O
(E)-Cinnamyl
O
BnN
NBn
O
O
3-(2,4-dibenzylimidazolidin-3-onyl)-3-oxopropionate
(33). To a solution of 32 (550 mg, 1.18 mmol, 1.0 equiv) in anhydrous
methylene chloride (50 mL) was added Dess-Martin periodinane (550
mg, 1.30 mmol, 1.1 equiv) and wet methylene chloride (5 mL). After stirring at 23 °C for 10 min, the
reaction was quenched with a solution of sodium thiosulfate (10% in saturated aqueous sodium
bicarbonate, 20 mL). The layers were separated and the organic layer was washed with saturated
aqueous sodium bicarbonate (5 mL), brine (2 mL), dried over anhydrous sodium sulfate, filtered,
concentrated and purified by silica gel (Davisil 633) column chromatography to afford pure 33 (445 mg,
81%) as pale yellow oil: Rf = 0.42 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 1738, 1705, 1652,
1573, 1446, 1151, 967, 737, 697; 1H NMR (400 MHz, CDCl3) δ 7.40-7.20 (m, 15H), 7.05 (s, 1H), 6.59
(d, J = 16.0 Hz, 1H), 6.16 (dt, J = 15.8, 6.5 Hz, 1H), 5.30 (s, 2H), 4.84 (s, 2H). 4.70 (d, J = 6.6 Hz, 2H),
3.54 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 179.7, 167.0, 153.6, 138.0, 136.2, 135.5, 135.1, 129.4, 128.9,
128.8, 128.6, 128.5, 128.4, 128.3, 127.7, 126.9, 123.9, 122.5, 121.5, 66.4, 48.0, 46.2, 45.6; HRMS(ES+)
calcd for C29H27N2O4 (M+H)+ 467.1971, found 467.1950.
S3
O
O
(E)-Cinnamyl
O
BnN
3-(2,4-dibenzylimidazolidin-3-onyl)-2-methyl-3-
oxopropionate (6). To a solution of crude 33 (420 mg, 0.90 mmol, 1.0
NBn Me
equiv) in anhydrous tetrahydrofuran was added sodium hydride (24 mg,
O
1 mmol, 1.1 equiv ) at 0 °C for 30 min and then 23 °C for 1.5 h before iodomethane (56.3 μL, 0.90
mmol, 1.0 equiv) was added. After stirring for another 6 h, the solvent was removed by vacuum. The
residue was dissolved with methylene chloride (50 mL), washed with saturated aqueous sodium
bicarbonate (10 mL), brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to
give crude 60. Synthesis of 6 directly from aldol reaction of aldehyde 31 and cinnamyl propionate gave
only modest yield. Purification by silica gel (Davisil 633) column chromatography afforded pure 10
(345 mg, 80%) as pale yellow oil: Rf = 0.51 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 1704, 1651,
1571, 1490, 1445, 1357, 1187, 1077, 967, 735, 698; 1H NMR (400 MHz, CDCl3) δ 7.38-7.17 (m, 15H),
7.10 (s, 1H), 6.52 (d, J = 15.9 Hz, 1H), 6.08 (dt, J = 15.8, 6.6 Hz, 1H), 5.34 (d, J = 14.5 Hz, 1H), 5.27 (d,
J = 14.6 Hz, 1H), 4.89 (d, J = 14.8 Hz, 1H), 4.73 (d, J = 15.0 Hz, 1H), 4.63 (t, J = 5.3 Hz, 2H), 3.76 (q, J
= 7.0 Hz, 1H), 1.34 (d, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 183.7, 170.3, 153.7, 138.0, 136.2,
135.5, 135.1, 129.3, 128.9, 128.7, 128.6, 128.5, 128.4, 128.3, 127.7, 126.9, 123.1, 122.5, 121.2, 66.3,
48.4, 48.0, 46.2, 13.9; HRMS(ES+) calcd for C30H29N2O4 (M+H)+ 481.2127, found 481.2125.
24
(3S*,7S*,8R*)-10,12-Dibenzyl-3-methyl-2,4,11-trioxo-8-phenyl-10,12-
23
25
diaza-5-oxatricyclo[7.3.0.03,7]dodec-1(9)-ene (7). β-Ketoester 6 (80.0 mg,
22
31
32
21
26
33
30
O
19
N
27
9
1
2
O
Me
13
O
17
0.167 mmol, 1.0 equiv) was dissolved in glacial acetic acid (10 mL) and
16
degassed by 3 freeze-pump-thaw cycles. Manganese(III) acetate dihydrate
H
N
29 28
18
20
10
12 11
14
8
3
H
7
4
6
O
5
15
(134 mg, 0.56 mmol, 3.0 equiv) was introduced while the mixture was kept
frozen at 0 °C. The reaction vessel was back-filled with argon and warmed
to 60 °C. After stirring at 60 °C for 3 h, acetic acid was removed by vacuum and the residue was
dissolved with methylene chloride (20 mL). The 10% sodium bisulfite solution was added until the
color of the solution became light yellow. The layers were separated and the organic layer was washed
with saturated sodium bicarbonate (2 mL), passed though a short pad of silica gel, washed with ethyl
acetate (20 mL), concentrated and purified by silica gel (Davisil 633) column chromatography to afford
pure 7 (50.3 mg, 63%) as pale yellow oil: Rf = 0.31 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2931,
1360, 1781, 1712, 1650, 1495, 1450, 1357, 1201, 1101, 1022, 751, 700; 1H NMR (400 MHz, CDCl3) δ
7.49 (d, J =7.2 Hz, 2H), 7.34-7.17 (m, 9H), 6.97 (m, 4H), 5.32 (s, 2H, H27), 5.14 (d, J = 15.6 Hz, 1H,
H20), 4.29 (t, J = 8.2 Hz, 1H, H6), 4.00 (d, J = 15.7 Hz, 1H, H20), 3.77-3.68 (m, 2H, H6, H8), 2.86 (dd, J
= 10.0, 8.5 Hz, 1H, H6), 1.24 (s, 3H, H13); 13C NMR (75 MHz, CDCl3) δ 177.8 (C2), 173.7 (C4), 154.1
(C11), 137.7 (CAr), 137.6 (CAr), 137.5 (C9), 135.6 (CAr), 129.9 (CAr), 129.3 (CAr), 128.8 (CAr), 128.7 (CAr),
S4
128.5 (CAr), 128.0 (CAr), 127.6 (CAr), 127.1 (CAr), 117.8 (C1), 68.8 (C6), 52.6 (C3), 49.9 (C7), 46.4 (C20),
45.5 (C27), 37.5 (C8), 22.8 (C13); HRMS(ES+) calcd for C30H37N2O4 (M+H)+ 479.1971, found 479.1992.
Cl
OH
(R,E)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-en-1-ol (34).
To a solution of
methyl 5-hydroxy-4-tri(iso-propyl)silyloxypent-2-enoate (McNulty, J.; Mao, J.
OTIPS
Tetrahedron Lett. 2002, 43, 3857–3861) (200 mg, 0.66 mmol, 1.0 equiv) in carbon tetrachloride (0.2
mL) and methylene chloride (4 mL) was added triphenylphosphine (347 mg, 1.32 mmol, 2.0 equiv).
After stirring for 30 min at 45 °C, the reaction was cooled to –78 °C and diisobutylaluminum hydride
(3.3 mL, 3.3 mmol, 5.0 equiv) was added. The reaction was stirred for another 15 min before quenched
with a solution of saturated Rochelle salt (10 mL). The mixture was stirred at 23 °C overnight, extracted
with methylene chloride (10 mL×3), dried over sodium sulfate, concentrated and purified by HPFC
Biotage system (FLASH silica gel) to afford pure 34 (74 mg, 90%) as colorless oil: Rf = 0.55 (25% ethyl
acetate-hexanes); FTIR (neat, cm–1) 3338, 2944, 2892, 2867, 1463, 1120, 1096, 882, 680; 1H NMR (400
MHz, CDCl3) δ 5.29-5.82 (m, 1H), 5.76-5.69 (m, 1H), 4.40 (dd, J = 12.0, 6.0 Hz, 1H), 4.14 (d, J = 5.1
Hz, 2H), 3.51 (dd, J = 9.7, 5.2 Hz, 1H), 3.39 (dd, J = 10.6, 6.6 Hz, 1H), 1.23-0.88 (m, 21H); 13C NMR
(100 MHz, CDCl3) δ 131.6, 131.1, 77.4, 77.1, 76.8, 73.0, 62.7, 48.0, 18.3, 12.4; HRMS(ES+) calcd for
C14H30ClO2Si (M+H)+ 293.1703, found 293.1694.
(R,E)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-enyl
O
BocHN
O
Cl
OTIPS
3-(tert-
butoxycarbamoyl)propionate (35). To a solution of 34 (120 mg, 0.41
mmol, 1.0 equiv) and Boc-β-alanine (77.6 mg, 0.41 mmol, 1.0 equiv) in
methylene chloride (10 mL) was added N,N′-dicyclohexylcarbodiimide (84.4 mg, 0.41 mmol, 1.0 equiv)
and 4-dimethylaminopyridine (1.5 mg, 0.012 mmol, 0.03 equiv). After stirring at 23 °C for 18 h, the
precipitates were filtered off and washed with methylene chloride (5 mL).
The solution was
concentrated to afford 35 (188 mg, 99%) as colorless oil: Rf = 0.76 (50% ethyl acetate-hexanes); FTIR
(neat, cm–1) 3389, 2944, 2867, 1716, 1504, 1390, 1366, 1249, 1170, 1066, 883, 680; 1H NMR (400
MHz, CDCl3) δ 5.85-5.78 (m, 1H), 5.00 (br, 1H), 4.67 (d, J = 4.8 Hz, 2H), 4.41 (dd, J = 11.5, 5.1 Hz,
1H), 3.52 (dd, J = 12.7, 5.0 Hz, 1H), 3.42-3.37 (m, 2H), 2.53 (t, J = 5.9 Hz, 2H), 1.43 (s, 9H), 1.21-0.85
(m, 21H); 13C NMR (100 MHz, CDCl3) δ 172.4, 156.0, 134.8, 126.3, 79.6, 73.0, 64.4, 48.6, 36.2, 34.8,
28.6, 18.2, 12.5; HRMS(ES+) calcd for C22H43ClNO5Si (M+H)+ 464.2599, found 464.2585.
OH O
O
BnN
NBn
O
(E)-(4R)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-enyl
NHBoc
Cl
OTIPS
2-(tert-
butoxycarbamoyl)methyl-3-(2,4-dibenzylimidazolidin-3-onyl)-3S5
hydroxypropionate (36). To a solution of ester 35 (163 mg, 0.35 mmol, 1.0 equiv) in tetrahydrofuran
(15 mL) cooled at –78 °C was added a solution of lithium hexamethyldisilazide (1.0 M in hexanes, 1.05
mL, 1.05 mmol, 3 equiv). The solution was stirred for 30 min before transferred via dry ice-cooled
cannula to a mixture of aldehyde 31 (82 mg, 0.28 mmol, 0.8 equiv) and boron trifluoride diethyl etherate
(0.088 mL, 0.70 mmol, 2.0 equiv) in tetrahydrofuran (5 mL) at –78 °C. After stirring for 45 min, the
reaction was quenched with saturated aqueous sodium bicarbonate solution (1 mL) and the solvent was
removed by vacuum. The residue was dissolved with methylene chloride (25 mL), washed with brine (5
mL), dried over anhydrous sodium sulfate, filtered, concentrated and purified by silica gel (Davisil 633)
column chromatography to afford pure 36 (142 mg, 67 % combined yield of a mixture of 1:1 ratio of
two diastereomers) as pale yellow oil.
Diastereomer A: Rf = 0.30 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3331, 2943, 2867, 1714, 1673,
1497, 1454, 1366, 1251, 1171, 883, 733, 700; 1H NMR (400 MHz, CDCl3) δ 7.36-7.22 (m, 10H), 6.16 (s,
1H), 5.75 (s, 1H), 5.07 (d, J = 15.8 Hz, 1H), 4.99 (d, J = 15.8 Hz, 1H), 4.80 (s, 1H), 4.61-4.54 (m, 1H),
4.43-4.37 (m, 3H), 3.51 (dd, J = 10.6, 4.9 Hz, 1H), 3.38 (dd, J = 10.6, 7.3 Hz, 1H), 3.27-3.20 (m, 1H),
3.21-3.15 (m, 1H), 2.87 (d, J = 6.0 Hz, 1H), 1.38 (s, 9H), 1.08-0.86 (m, 21 H);
13
C NMR (100 MHz,
CDCl3) δ 172.9, 156.0, 154.0, 137.9, 137.0, 135.3, 129.0, 128.9, 128.1, 128.0, 127.7, 127.3, 125.7, 122.8,
108.4, 80.0, 72.8, 65.0, 64.7, 50.0, 48.6, 47.4, 45.3, 40.5, 28.5, 18.2, 12.5; HRMS(ES+) calcd for
C40H59ClN3O7Si (M+H)+ 756.3811, found 756.3785.
Diastereomer B: Rf = 0.25 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3339, 2925, 2866, 1719, 1672,
1497, 1453, 1365, 1169, 111, 737, 699; 1H NMR (400MHz, CDCl3) δ 7.35-7.23 (m, 10H), 6.13 (s, 1H),
5.69-5.67 (m, 2H), 5.09 (d, J = 15.6Hz, 1H), 4.97 (d, J = 15.7 Hz, 1H), 4.86-4.74 (m, 3H), 4.60-4.58 (m,
2H), 4.46-4.42 (m, 1H), 4.38-4.35 (m, 1H), 4.29-4.26 (m, 1H), 3.83-3.76 (m, 1H), 3.51(dd, J = 10.8, 4.7
Hz, 1H), 3.39-3.34 (m, 1H), 2.70 (d, J = 9.2 Hz, 1H), 1.39 (s, 9H), 1.08-0.86 (m, 21 H); 13C NMR (100
MHz, CDCl3) δ 171.6, 157.8, 154.0, 137.9, 137.1, 135.5, 129.0, 128.8, 128.1, 128.0, 127.9, 127.5, 127.3,
125.8, 123.1, 108.1, 81.0, 72.7, 64.6, 62.5, 49.8, 48.5, 47.3, 45.2, 38.9, 29.6, 28.4, 18.2, 12.5;
HRMS(ES+) calcd for C40H59ClN3O7Si (M+H)+ 756.3811, found 756.3797.
O
O
BnN
NBn
O
(E)-(4R)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-enyl
O
NHBoc
Cl
OTIPS
2-(tert-
butoxycarbamoyl)methyl-3-(2,4-dibenzylimidazolidin-3-onyl)-3oxopropionate (8). To a solution of crude 36 (135 mg, 0.179 mmol,
1.0 equiv) in anhydrous methylene chloride (10 mL) was added Dess-Martin periodinane (80 mg, 0.188
mmol, 1.05 equiv) and wet methylene chloride (2 mL). After stirring for 15 min, the reaction was
quenched with a solution of sodium thiosulfate (1.0 M in saturated aqueous sodium bicarbonate, 5 mL).
The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate
S6
(5 mL), brine (5 mL), dried over anhydrous sodium sulfate, filtered, concentrated afford crude 8 (123
mg, 91%) which can be used without purification. Alternatively, 8 can be purified by silica gel (Davisil
633) column chromatography as pale yellow oil (108 mg, 80%): Rf = 0.64 (25% ethyl acetate-hexanes);
FTIR (neat, cm–1) 3340, 2943, 2866, 1708, 1651, 1570, 1497, 1445, 1249, 1168, 1116, 699; 1H NMR
(400 MHz, CDCl3) δ 7.44 (s, 1H), 7.39-7.22 (m, 10H), 5.73-5.71 (m, 2H), 5.31 (dd, J = 29.2, 14.6 Hz,
2H), 4.88 (d, J = 14.6 Hz, 1H), 4.60 (d, J = 14.6 Hz, 1H), 4.74 (br, 1H), 4.55-4.50 (m, 2H). 4.36-4.35 (m,
1H), 4.14 (t, J = 6.8Hz, 1H), 3.52-3.46 (m, 3H), 3.35 (dd, J = 10.8, 6.8 Hz, 1H), 1.37 (s, 9H), 1.06-0.86
(m, 21H); 13C NMR (100 MHz, CDCl3) δ 182.0, 168.1, 156.1, 153.6, 138.0, 135.5, 135.2, 129.4, 128.7,
128.6, 128.2, 127.6, 125.7, 125.0, 121.6, 80, 72.8, 65.3, 48.6, 48.2, 46.2, 40.5, 28.5, 18.2, 12.5;
HRMS(ES+) calcd for C40H57ClN3O7Si (M+H)+ 754.3654, found 754.3623.
(R,Z)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-en-1-ol (37). Prepared as for 34 and
Cl
TIPSO
obtained as colorless oil (80.8 mg, 82%): Rf = 0.55 (25% ethyl acetate-hexanes); FTIR
OH
(neat, cm–-1) 3351, 3000, 2892, 2867, 1463, 1116, 1092, 882, 681; 1H NMR (400 MHz, CDCl3) δ 5.75
(dt, J = 12.1, 6.0 Hz, 1H), 5.50 (dd, J = 11.2, 8.6 Hz, 1H), 3.56 (dd, J = 10.6, 5.4 Hz, 1H), 3.36 (dd, J =
10.6, 7.5 Hz, 1H), 1.21-0.85 (m, 21H);
13
C NMR (100 MHz, CDCl3) δ 132.5, 131.0, 69.2, 29.3, 48.3,
18.0, 12.3; HRMS(ES+) calcd for C14H30ClO2Si (M+H)+ 293.1703, found 293.1693.
Cl
OTIPS
O
BocHN
O
(R,Z)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-enyl
butoxycarbamoyl)propionate (38).
3-(tert-
Prepared as for 35 from the
corresponding (Z)-allylic alcohol and obtained as colorless oil (146 mg, 99%): Rf = 0.78 (50% ethyl
acetate-hexanes); FTIR (neat, cm–1) 3369, 2944, 2893, 2867, 1736, 1718, 1507, 1248, 1169, 1065, 882,
682; 1H NMR (400 MHz, CDCl3) δ 5.70-5.58 (m, 2H), 5.00 (br, 1H), 4.76-4.61 (m, 3H), 3.55 (dd, J =
10.8, 5.3 Hz, 1H), 3.40-3.36 (m, 3H), 2.53 (t, J = 6.0 Hz, 2H), 1.43 (s, 9H), 1.11-0.85 (m, 21H);
13
C
NMR (100 MHz, CDCl3) δ 172.3, 155.9, 135.0, 125.8, 79.5,69.3, 60.8, 48.5, 36.2, 34.7, 28.6, 18.1, 12.4;
HRMS(ES+) calcd for C22H43ClNO5Si (M+H)+ 464.2599, found 464.2583.
OH O
O
BnN
NBn
O
NHBoc
Cl
OTIPS
(Z)-(4R)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-enyl
2-(tert-
butoxycarbamoyl)methyl-3-(2,4-dibenzylimidazolidin-3-onyl)-3hydroxypropionate (39). Prepared as for 36 and obtained as pale yellow
oil (108 mg, 69% combined yield of a mixture of 1:1 ratio of two diastereomers).
Diastereomer A: Rf = 0.30 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3338, 2942, 2866, 1712,
1670, 1500, 1461, 1367, 1251, 885, 732, 699; 1H NMR (400 MHz, CDCl3) δ 7.40-7.22 (m, 10H), 6.11
(d, J = 4.2 Hz, 1H), 5.52-5.42 (m, 2H), 5.10 (d, J = 15.8 Hz, 1H), 5.05 (d, J = 15.9 Hz, 1H), 4.85 (d, J =
S7
15.0 Hz, 1H), 4.79 (d, J = 15.0 Hz, 1H), 4.69-451 (m, 5H), 4.43 (br, 1H), 3.51 (dd, J = 10.7, 5.2 Hz,
1H), 3.40-3.32 (m, 2H), 3.23-3.17 (m, 2H), 2.87 (d, J = 6.0 Hz, 1H), 1.38 (s, 9H), 1.08-0.86 (m, 21 H);
13
C NMR (100 MHz, CDCl3) δ 172.9, 156.0, 154.0, 137.9, 137.0, 135.3, 129.4, 129.0, 128.7, 128.6,
128.2, 127.8, 127.6, 127.3, 125.4, 122.9, 108.2, 80.0, 69.3, 64.7, 61.4, 49.0, 48.6, 47.4, 45.3, 40.5, 28.5,
18.2, 12.4; HRMS(ES+) calcd for C40H59ClN3O7Si (M+H)+ 756.3811, found 756.3845.
Diastereomer B: Rf = 0.20 (50% ethyl acetate-hexanes); FTIR (neat, cm–1)3306, 2943, 2865, 1665, 1496,
1452, 1365, 1251, 1164, 882. 1H NMR (400 MHz, CDCl3) δ 7.35-7.15 (m, 10H), 6.11 (s, 1H), 5.51-5.46
(m, 1H), 5.32-5.25 (m, 1H), 5.10 (d, J = 16.1Hz, 1H), 4.94 (dd, J = 15.8, 3.7 Hz, 1H), 4.84-4.75 (m,
2H), 4.63-4.50 (m, 4H), 4.47-4.38 (m, 1H), 3.81-3.75 (m, 1H), 3.54-3.50 (m, 1H), 3.35-3.30 (m, 1H),
3.22-3.18 (m, 1H), 2.69(m, 1H), 1.39 (s, 9H), 1.08-0.86 (m, 21 H);
13
C NMR (100 MHz, CDCl3) δ
171.6, 157.8, 154.0, 137.9, 137.1, 135.2, 129.0, 128.8, 128.5,128.3, 128.1, 128.0, 127.5, 127.3, 125.4,
123.2, 108.1, 81.0, 69.3, 62.5, 61.1, 49.8, 48.4, 47.4, 45.2, 40.0, 28.4, 18.1, 12.4; HRMS(ES+) calcd for
C40H59ClN3O7Si (M+H)+ 756.3811, found 756.3839.
O
O
Cl
OTIPS
O
BnN
NBn
2-(tert-
butoxycarbamoyl)methyl-3-(2,4-dibenzylimidazolidin-3-onyl)-3oxopropionate (11). Prepared as for 8 and obtained as pale yellow oil
NHBoc
O
(Z)-(4R)-5-Chloro-4-tri(iso-propyl)silyloxypent-2-enyl
(90 mg, 92%): Rf = 0.64 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3332, 2944, 2866, 1738, 1710,
1651, 1571, 1446, 1365, 1249, 1168, 700; 1H NMR (400 MHz, CDCl3) δ 7.43-7.18 (m, 11H), 5.53 (t, J
=8.4 Hz, 1H), 5.45-5.39 (m, 1H), 5.30 (d, J = 14.7 Hz, 1H), 5.26 (d, J = 14.7 Hz, 1H), 4.95 (d, J =14.8
Hz, 1H), 4.84 (d, J = 14.8 Hz, 1H), 4.77-4.74 (m, 1H), 4.70-4.50 (m, 3H), 4.13 (t, J = 6.7 Hz, 1H), 3.513.42 (m, 3H), 3.36-3.30 (m, 1H), 1.39 (s, 9H), 1.03-0.85 (m, 21H);
13
C NMR (100 MHz, CDCl3) δ
181.9, 168.2, 156.2, 153.7, 137.9, 135.5, 135.2, 129.3, 128.7, 128.6, 128.2, 127.6, 125.3, 125.1, 121.6;
HRMS(ES+) calcd for C40H57ClN3O7Si (M+H)+ 754.3654, found 754.3668.
20
27
28
26
17
O
10 16 15
12 11
25 24
23
27
N
H
N
9
1
2
O13
BocHN O
8
3
7
4
6
O
5
Cl
26
23
O
10 16 15
N
H
N
9
1
2
9
butoxycarbamoyl)methyl-10,12-dibenzyl-
17
12 11
25 24
OTIPS
18
22
29
14
H
28
(3R,7S,8S)-3-(tert-
19
21
18
22
29
20
19
21
O13
BocHN O
8
3
H
7
4
6
O
Cl
2,4,11-trioxo-8-[(R)-2-chloro-1-tri(iso-
14
OTIPS
10
propyl)silyloxyethyl]-10,12-diaza-5oxatricyclo[7.3.0.03,7]dodec-1(9)-ene (9) and
5
(3S,7R,8R)-3-(tert-
butoxycarbamoyl)methyl-10,12-dibenzyl-2,4,11-trioxo-8-[(R)-2-chloro-1-tri(isopropyl)silyloxyethyl]-10,12-diaza-5-oxatricyclo[7.3.0.03,7]dodec-1(9)-ene (10).
Prepared as for 7
from 8 (80.0 mg) by reacting with manganese(III) acetate at 60 °C for 12 h, or from 11 (66.2 mg) by
S8
reacting with manganese(III) acetate at 80 °C for 12 h. Purification by silica gel (Davisil 633) column
chromatography afforded 9 (31.9 mg, 40%) and 10 (15.2 mg, 19%) from 7 (80.0 mg), and 9 (13.1 mg,
20%) and 10 (19.8 mg, 30%) from 11 (66.2 mg) as pale yellow oils.
9: Rf = 0.18 (20% ethyl acetate-hexanes); FTIR (neat, cm–1) 2918, 1778, 1714, 1651, 1462, 1455, 1265,
1173, 1066, 882, 740, 703; 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 6.6 Hz, 2H), 7.38-7.22 (m, 8H),
5.36 (d, J = 15.4 Hz, 1H, H16), 5.20 (d, J = 14.3 Hz, 1H, H23), 5.10 (d, J = 14.3 Hz, 1H, H23), 4.89-4.83
(m, 1H, NH), 4.56 (d, J = 15.4Hz, 1H, H16), 4.31 (t, J = 11.0 Hz, 1H, H15), 4.20-4.16 (m, 1H, H14), 4.134.08 (m, 2H, H13, H6), 3.69 (dd, J =9.8, 4.3 Hz, 2H, H13, H15), 3.36 (t, J = 9.5 Hz, 1H, H7), 3.18 (s, 1H,
H8), 3.12 (t, J =9.3 Hz, 1H, H6), 1.38 (s, 9H), 1.05-0.72 (m, 21H);
13
C NMR (100 MHz, CDCl3) δ 174.6
(C2), 172.7 (C4), 156.7 (CBoc), 154.1 (C11), 137.4 (CAr), 137.1 (CAr), 135.9 (C9), 129.4 (CAr), 128.8 (CAr),
128.7 (CAr), 128.0 (CAr), 127.8 (CAr), 120.6 (C1), 80.1 (CBoc), 72.7 (C14), 69.8 (C6), 60.6 (C3), 46.2 (C23),
46.0 (C16), 44.6 (C13), 43.6 (C15), 35.1 (C8), 33.8 (C7), 28.3 (CBoc), 18.0 (CTIPS), 12.8 (CTIPS); HRMS(ES+)
calcd for C40H55ClN3O7Si (M+H)+ 752.3498, found 752.3523.
10: Rf = 0.26 (20% ethyl acetate-hexanes); FTIR (neat, cm–1) 2947, 2918, 1783, 1713, 1649, 1469, 1247,
1172, 1083, 974, 790, 738, 701; 1H NMR (400 MHz, CDCl3) δ 7.53-7.00 (m, 2H), 7.34-7.21 (m, 8H),
5.36 (d, J = 15.4 Hz, 1H, H16), 5.22 (d, J = 14.3 Hz, 1H, H23), 5.15 (d, J = 14.3 Hz, 1H, H23), 5.00 (d, J =
15.4 Hz, 1H, H16), 4.73 (d, J = 9.3 Hz, 1H, H14), 4.10 (t, J = 8.8 Hz, 1H, H6), 3.88-3.80 (m, 3H, H13, H15),
3.65 (d, J = 14.6 Hz, 1H, H15), 3.20 (d, J = 9.3 Hz, 1H, H7), 3.14 (dd, J = 10.9, 9.2 Hz, 1H, H6), 2.83 (t, J
= 9.8 Hz, 1H, H8), 1.39 (s, 9H), 1.07-0.85 (m, 21H); 13C NMR (100 MHz, CDCl3) δ 173.3 (C2), 172.4
(C4), 156.8 (CBoc), 153.8 (C11), 139.9 (CAr), 137.5 (CAr), 136.7 (C9), 129.3 (CAr), 129.2 (CAr), 128.7 (CAr),
128.4 (CAr), 128.0 (CAr), 127.5 (CAr), 117.8 (C1), 80.7 (CBoc), 73.2 (C14), 68.2 (C6), 59.5 (C3), 49.3 (C13),
46.1 (C23), 46.0 (C16), 45.0 (C15), 35.9 (C8), 34.8 (C7), 28.4 (CBoc), 18.0 (CTIPS), 12.8 (CTIPS); HRMS(ES+)
calcd for C40H55ClN3O7Si (M+H)+ 752.3498, found 752.3518.
O
OTIPS
BocHN
O
(E)-(1S,3S)-3-tri(iso-propyl)silyloxycyclopent-4-enyl
butoxycarbamoyl)propionate (40).
3-(tert-
To a solution of (1R,3S)-(+)-1-
acetoxy-3-hydroxycyclopent-4-ene (100 mg, 0.70 mmol, 1.0 equiv) in methylene chloride (10 mL) was
added triisopropylsilyloxy triflate (0.23 mL, 0.84 mmol, 1.2 equiv) and 2,6-lutidine (0.12 mL, 1.06
mmol, 1.5 equiv) successfully. After stirring at 23 °C for 18 h, the reaction was washed with water (1
mL), 1 N HCl (1 mL×3) and saturated sodium bicarbonate (1 mL×2). The solvent was removed by
vacuum, and the residue was dissolved with tetrahydrofuran (7.5 mL). Lithium hydroxide (0.35 N in
H2O, 6 mL) was then introduced and the reaction was stirred at 23 °C for 18 h. The solvent was
removed by vacuum. The residue was dissolved with methylene choride (20 mL) and washed with
saturated ammonium chloride (5 mL). The organic layer was dried over anhydrous sodium sulfate and
S9
concentrated. To a solution of the crude alcohol in tetrahydrofuran (10 mL) was added Boc-β-alanine
(530 mg, 2.8 mmol, 4.0 equiv), triphenylphosphine (734 mg. 2.8 mmol, 4.0 equiv) followed by diethyl
azodicarboxylate (487 mg, 2.8 mmol, 4.0 equiv) slowly at 0 °C. After stirring at 23 °C for 5 h, the
solvent was removed by vacuum and the residue was purified by silica gel (Davisil 633) column
chromatography to afford pure 40 (175 mg, 58 % over three steps) as pale yellow oil: Rf = 0.42 (20%
ethyl acetate-hexanes); FTIR (neat, cm–1) 3382, 2943, 2867, 1721, 1505, 1463, 1366, 1284, 1172, 1066,
882; 1H NMR (400 MHz, CDCl3) δ 6.10-6.08 (m, 1H), 5.94 (dd, J = 4.0, 0.7 Hz, 1H), 5.81-5.79 (m, 1H),
5.14-512 (m, 1H), 4.99 (br, 1H), 3.37 (dd, J = 11.8-5.9 Hz, 2H), 2.47 (t, J = 5.9 Hz, 2H), 2.22-2.16 (m,
1H), 2.12-2.06 (m, 1H), 1.43 (s, 9H), 1.13-0.88 (m, 21H); 13C NMR (100 MHz, CDCl3) δ 172.6, 155.9,
141.6, 131.2, 79.7, 19.5, 77.7, 41.6, 36.3, 34.9, 28.6, 18.1, 12.3; HRMS(ES+) calcd for C22H41NNaO5Si
(M+Na)+ 450.2652, found 450.2656.
O
O
OTIPS
BnN
O
NBn
NHBoc
O
(E)-(1S,3S)-3-tri(iso-propyl)silyloxycyclopent-4-enyl
2-(tert-
butoxycarbamoyl)methyl-3-(2,4-dibenzylimidazolidin-3-onyl)-3oxopropionate (12). Prepared as for 8 and obtained as pale yellow oil
(90 mg, 59%): Rf = 0.59 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3332, 2944, 2866, 1738, 1710,
1651, 1571, 1446, 1365, 1249, 1168, 700; 1H NMR (400 MHz, CDCl3) δ 7.43-7.18 (m, 11H), 5.53 (t, J
=8.4 Hz, 1H), 5.45-5.39 (m, 1H), 5.30 (d, J = 14.7 Hz, 1H), 5.26 (d, J = 14.7 Hz, 1H), 4.95 (d, J =14.8
Hz, 1H), 4.84 (d, J = 14.8 Hz, 1H), 4.77-4.74 (m, 1H), 4.70-4.50 (m, 3H), 4.13 (t, J = 6.7 Hz, 1H), 3.513.42 (m, 3H), 3.36-3.30 (m, 1H), 1.39 (s, 9H), 1.03-0.85 (m, 21H);
13
C NMR (100 MHz, CDCl3) δ
181.9, 168.2, 156.2, 153.7, 137.9, 135.5, 135.2, 129.3, 128.7, 128.6, 128.2, 127.6, 125.3, 125.1, 121.6;
HRMS(ES+) calcd for C40H57ClN3O7Si (M+H)+ 754.3654, found 754.3668.
(1R,8R,9S,11R,14S)-1-(tert-butoxycarbamoyl)methyl-4,6-dibenzyl-2,5,13-
O
BnN
NBn
H OTIPS
H
O
BocHN O
O
trioxo-9-tri(iso-propyl)silyloxy-4,6-diaza-12oxatetracyclo[6.5.1.03,7.011,14]tetradec-3(7)-ene (13).
H
Prepared as for 7 by
reacting 12 (75 mg) with manganese(III) acetate at 60 °C for 16 h and obtained as
white solid (45 mg, 60%): Rf = 0.72 (50% ethyl acetate-hexanes);. FTIR (neat, cm–1) 2944, 2867, 1757,
1715, 1645, 1498, 1467, 1365, 1250, 1168, 1122, 882, 804; 1H NMR (400 MHz, CDCl3) δ 7.35-7.17 (m,
10H), 5.33 (d, J = 14.7 Hz, 1H), 5.28-5.18 (m, 3H), 4.94 (t, J = 5.8 Hz, 1H), 4.69 (br, 1H), 4.35-4.29 (m,
1H), 3.72-3.67 (m, 2H), 3.58 (dd, J = 13.9, 7.7 Hz, 1H), 3.10 (t, J = 9.9 Hz, 1H), 2.53 (dd, J = 13.5, 5.1
Hz, 1H), 1.98-1.91 (m, 1H), 1.36 (s, 9H), 1.09-0.99 (m, 21H);
13
C NMR (100 MHz, CDCl3) δ 175.9,
171.8, 156.9, 153.7, 140.7, 137.7, 136.5, 129.3, 128.8, 128.3, 127.8, 127.2, 116.1, 80.6, 80.1, 79.4, 58.9,
S10
46.8, 46.0, 45.9, 42.3, 40.9, 28.4, 18.2, 17.9, 12.7; calcd for C40H53N3NaO7Si (M+Na)+ 738.3550, found
738.3544.
4-Chloro-1,3-dibenzyl-5-formylimidazolidin-2-one (41). To a solution of 31 (2.92 g, 10
O
BnN
Cl
NBn
mmol, 1.0 equiv) in carbon tetrachloride (50 mL) was added N-chlorosuccinimide (1.34
CHO
mL, 10 mmol, 1.0 equiv). The solvent was removed by vacuum after stirring at 80 °C for
16 h and the residue was purified by silica gel (Davisil 633) column chromatography to afford pure 41
(2.65 g, 81%) as pale yellow oil: Rf = 0.53 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3032, 1716,
1659, 1562, 1442, 1353, 1168, 880, 743, 770; 1H NMR (400 MHz, CDCl3) δ 9.49 (s, 1H), 7.44-7.25 (m,
10H), 5.26 (s, 2H), 4.98 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 175.6, 151.7, 137.4, 135.3, 129.2, 128.8,
128.7, 128.6, 128.2, 128.1, 127.9, 118.2, 46.0, 15.9; HRMS(ES+) calcd for C18H16ClN2O2 (M+H)+
327.0900, found 327.0905.
Cl
O
O
(E)-Cinnamyl
O
BnN
3-(5-chloro-2,4-dibenzylimidazolidin-3-onyl)-2-
methyl-3-oxopropionate (14). Prepared as for 6 and obtained as pale
NBn Me
yellow oil (72 mg, 51% over three steps): Rf = 0.52 (50% ethyl acetate-
O
hexanes); FTIR (neat, cm–1) 1714, 1652, 1542, 1495, 1440, 1350, 1174, 967, 744, 698; 1H NMR (400
MHz, CDCl3) δ 7.35-7.20 (m, 15H), 6.55 (d, J = 15.7 Hz, 1H), 6.10 (dt, J = 15.7, 6.6 Hz, 1H), 5.38 (d, J
= 14.7 Hz, 1H), 5.28 (d, J = 14.7 Hz, 1H), 5.00 (d, J = 15.2 Hz, 1H), 4.92 (d, J = 15.4 Hz, 1H), 4.734.60 (m, 2H), 4.29 (q, J = 7.1 Hz, 1H), 1.32 (d, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 185.2,
170.1, 152.1, 137.7, 136.2, 135.5, 134.9, 129.1, 128.9, 128.7, 128.5, 128.4, 128.3, 128.1, 127.7, 126.9,
122.7, 121.6, 118.3, 66.2, 49.8, 46.5, 45.9, 13.8; HRMS(ES+) calcd for C30H28ClN2O4 (M+H)+ 515.1738,
found 515.1714.
Bn
N
Bn
N O
O
BnN
O
+
H
Me
O
Cl
H
O
NBn
Me Cl
O
O
15
O
O
H
16
(5R*,1’S*,5’S*,6’R*)-Spiro{(1,3-dibenzylimidazolin-2,4dione)-5,7’-(2’,8’-dioxo-1’-methyl-6’-phenyl-3’oxabicycle[3.3.0]octane)}
(15)
and
3-(5-chloro-2,4-
dibenzylimidazolidin-3-onyl)carbonyl-3-methyl-4-
[chloro(phenyl)methyl]dihydro-2(3H)furanone (16). Prepared as for 7 by reacting 14 (18 mg) with
manganese(III) acetate at 60 °C for 2 h to give 15 (7 mg, 40%) and 16 (9 mg, 47%) as pale yellow oils.
15: Rf = 0.63 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2930, 1791, 1711, 1440, 1143, 750, 700;
1
H NMR (400 MHz, CDCl3) δ 7.39-7.37 (m, 3H), 7.29-7.28 (m, 2H), 7.19-7.12 (m, 4H), 7.01 (t, J = 7.8
Hz, 2H), 6.80 (d, J = 7.0 Hz, 2H), 6.57 (d. J =7.3 Hz, 2H), 5.07 (d, J = 15.3 Hz, 2H), 4.47 (s, 2H), 4.36
(dd, J = 9.8, 5.2, 1H), 3.99-3.94 (m, 2H), 3.71 (dd, J = 11.7, 5.1 Hz, 1H), 3.08 (d, J = 11.7 Hz, 1H), 1.67
S11
(s, 3H);
13
C NMR (75 MHz, CDCl3) δ 201.0, 172.2, 168.3, 156.6, 136.3, 134.9, 132.1, 129.8, 129.5,
129.1, 129.0, 128.8, 127.8, 127.5, 80.6, 68.7, 58.4, 49.7, 45.8, 45.5, 42.9, 18.8; HRMS(ES+) calcd for
C30H30N3O5 (M+NH4)+ 512.2185, found 512.2181.
16: Rf = 0.62 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 1777, 1714, 165, 1539, 1496, 1443, 1353,
1174, 1021, 798, 736, 698; 1H NMR (400 MHz, C6D6) δ 7.56 (d, J = 7.6 Hz, 2H), 7.13-6.80 (m, 9H),
6.79-6.75 (m, 2H), 6.72-6.70 (m, 2H), 4.79 (d, J = 14.8 Hz, 1H), 4.70 (d, J = 15.4 Hz, 1H), 4.22 (d, J =
1.7 Hz, 1H), 4.17 (d, J = 9.6 Hz, 1H), 4.08 (d, J = 15.6 Hz, 1H), 3.98 (d, J = 14.6 Hz, 1H), 3.65-3.62 (m,
2H), 1.06 (s, 3H); 13C NMR (75 MHz, C6D6) δ 183.4, 174.3, 152.0, 138.2, 138.1, 136.3, 129.8, 129.5,
129.3, 129.1, 128.9, 128.3, 128.7, 128.5, 128.4, 128.2, 127.9, 127.6, 1273, 117.9, 117.7, 68.8, 60.8, 57.5,
50.7, 47.6, 45.2, 15.2; HRMS(ES+) calcd for C30H27Cl2N2O4 (M+H)+ 549.1348, found 549.1367.
Cl
O
(E)-3-(4-Nitrophenyl)prop-2-enyl
O
O
BnN
3-(5-chloro-2,4-
dibenzylimidazolidin-3-onyl)-2-methyl-3-oxopropionate
NBn Me
NO2
O
(17).
Prepared as for 6 and obtained as pale yellow oil (52 mg, 46% over
three steps): Rf = 0.55 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2937, 1714, 1651, 1516, 1441,
1342, 1181, 1019, 860, 700; 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.4 Hz, 2H), 7.52-7.17 (m, 12H),
6.59 (d, J = 15.8 Hz, 1H), 6.30 (dt, J = 15.8, 5.8 Hz, 1H), 5.37 (d, J = 14.7 Hz, 1H), 5.29 (d, J = 14.7 Hz,
1H), 5.00 (dd, J = 18.7 , 5.4 Hz, 2H), 4.71 (d, J = 5.9 Hz, 2H), 4.32 (t, J = 7.1Hz, 1H), 1.32 (d, J = 16.4
Hz, 3H);
13
C NMR (75 MHz, CDCl3) δ 185.3, 169.9, 152.1, 147.5, 142.7, 137.7, 135.4, 133.9, 131.7,
129.2, 128.6, 128.5, 128.3, 128.1, 127.8, 127.4, 127.2, 124.2, 121.8, 118.2, 65.3, 49.8, 46.6, 46.0, 13.9;
HRMS(ES+) calcd for C30H29N2O4 (M+H)+ 481.2127, found 481.2125.
Bn
N O
O
BnN
O
H
Bn
N
Cl
+
H
Me
O
NO2
O
18
2,4-dione)-5,7’-[2’,8’-dioxo-1’-methyl-6’-(4-
NBn
Me Cl
O
O
(5R*,1’S*,5’S*,6’R*)-Spiro{(1,3-dibenzylimidazolin-
O
O
H
19
nitrophenyl)-3’-oxabicycle[3.3.0]octane]} (18) and 3NO2
(5-chloro-2,4-dibenzylimidazolidin-3-onyl)carbonyl3-methyl-4-[chloro(4-nitrophenyl)methyl]dihydro-
2(3H)furanone (19). Prepared as for 7 by reacting 17 (20 mg) with manganese(III) acetate at 60 °C for
3 h to give 18 (6.5 mg, 34%) and 19 (7.5 mg, 35%) as pale yellow oils.
18: Rf = 0.61 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2925, 1792, 1712, 1523, 1442, 1384, 1143,
1077, 735, 697; 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.4 Hz, 2H), 7.50-7.15 (m, 6H), 7.09 (t, J =
7.3 Hz, 2H), 6.91 (d, J = 7.0 Hz, 2H), 6.54 (d, J = 8.8 Hz, 2H), 5.22 (d, J = 15.4 Hz, 1H), 4.52 (dd, J =
11.7, 5.1 Hz, 1H), 4.41-4.53 (m, 2H), 3.89 (d, J = 10.2 Hz, 1H), 3.85 (d, J = 15.4 Hz, 1H), 3.70 (d, J =
15.4 Hz, 1H), 3.13 (d, J = 11.3 Hz, 1H), 1.71 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 200.0, 171.7, 167.7,
S12
156.3, 147.9, 139.0, 136.5, 134.8, 129.9, 129.8, 129.2, 128.8, 128.3, 128.2, 124.3, 123.7, 80.2, 68.4, 58.4,
49.4, 45.9, 45.3, 43.1, 18.6; HRMS(ES+) calcd for C30H25N3NaO7 (M+Na)+ 562.1590, found 562.1572.
19: Rf = 0.54 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2924, 1778, 1713, 1644, 1525, 1442, 1348,
1021, 733, 697; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.8 Hz, 2H), 7.43-7.17 (m, 10H), 7.10 (d, J =
6.6 Hz, 2H), 5.08 (d, J = 15.4 Hz, 1H), 4.97 (d, J = 15.4 Hz, 1H), 4.93 (d, J = 8.8 Hz, 1H), 4.80 (d, J =
14.7 Hz, 1H), 4.62-4.57 (m, 2H), 4.30 (t, J = 8.8 Hz, 1H), 3.72 (q, J = 8.3 Hz, 1H), 1.43 (s, 3H);
13
C
NMR (75 MHz, CDCl3) δ 183.6, 175.0, 152.1, 148.3, 144.6, 140.0, 135.3, 129.3, 128.7, 128.6, 128.4,
128.3, 128.0, 127.9, 127.7, 124.4, 119.0, 117.5, 59.5, 57.1, 50.0, 47.0, 46.2, 15.8; HRMS(ES+) calcd for
C30H26Cl2N3O6 (M+H)+ 594.1199, found 594.1208.
O
Cl
O
(E)-methyl
Me
O
BnN
3-(5-chloro-2,4-dibenzylimidazolidin-3-onyl)-2-methyl-3-
oxopropionate (20). Prepared as for 6 from (E)-but-2-enol and obtained as
NBn Me
pale yellow oil (48 mg, 48% over three steps): Rf = 0.68 (50% ethyl
O
acetate-hexanes); FTIR (neat, cm–1) 1717.8, 1657.6, 1651.6, 1544.5, 1455.1, 1441.2, 1352.4, 1172.9,
1019.7, 967.8, 745.0, 700.4; 1H NMR (400 MHz, CDCl3) δ 7.40-7.20 (m, 10H), 5.74-5.64 (m, 1H),
5.48-5.34 (m, 1H), 5.28 (d, J = 14.7 Hz, 1H), 5.00 (dd, J = 20.2, 14.7 Hz, 2H), 4.50-4.37 (m, 2H), 4.25
(dd, J = 14.3, 7.3Hz, 1H), 1.67 (d, J = 6.7 Hz, 3H), 1.29 (d, J = 7.3 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ 185.3, 170.1, 152.1, 137.7, 135.5, 132.0, 129.1, 128.6, 128.5, 128.3, 128.1, 127.7, 124.8, 121.6, 118.3,
66.3, 49.8, 46.5, 46.0, 18.0, 13.8; HRMS(ES+) calcd for C25H25ClN2NaO4 (M+Na)+ 475.1400, found
475.1400.
Bn
N
Bn
N O
O
BnN
O
H
O
H
Me
O
Cl
Me +
21
5,7’-(2’,8’-dioxo-1’-methyl-6’-methyl-3’-oxabicycle[3.3.0]octane)}
NBn
Me Cl
Me
O
O
(5R*,1’S*,5’S*,6’S*)-Spiro{(1,3-dibenzylimidazolin-2,4-dione)-
O
H
O
22
(21) and 3-(5-chloro-2,4-dibenzylimidazolidin-3-onyl)carbonyl-3methyl-4-(2-chloroethyl)dihydro-2(3H)furanone (22). Prepared as
for 7 by reacting 20 (20 mg) with manganese(III) acetate at 60 °C for 2.5 h to give 21 (4.6 mg, 25%) and
22 (7.4 mg, 36%) as pale yellow oils.
21: Rf = 0.59 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2930, 1790, 1711, 1440, 1415, 1030, 699;
1
H NMR (400 MHz, CDCl3) δ 7.37-7.16 (m, 10H), 5.10 (d, J = 15.4 Hz, 1H), 4.67 (d, J = 2.2 Hz, 2H),
4.33 (dd, J = 9.8, 5.5 Hz, 1H), 3.97 (d, J = 9.9 Hz, 1H), 3.86 (d, J = 15.4 Hz, 1H), 2.96 (dd, J = 11.0, 5.1
Hz, 1H), 1.68-1.57 (m, 1H), 1.53 (s, 3H), 0.75 (d, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 201.3,
172.2, 168.3, 156.7, 136.3, 135.5, 129.3, 129.1, 129.0, 128.8, 128.6, 128.3, 128.2, 128.1, 128.0, 79.5,
68.6, 57.9, 46.9, 45.2, 43.2, 39.2, 18.9, 11.0; HRMS(ES+) calcd for C25H25N2O5 (M+H)+ 433.1764,
found 433.1768.
S13
22: Rf = 0.63 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2922, 1777, 1713, 1644, 1537 ,1442, 1348,
1203, 1094, 1014, 909, 797, 733, 699; 1H NMR (400 MHz, CDCl3) δ 7.40-7.17 (m, 10H), 5.39 (d, J =
14.6 Hz, 1H), 5.26 (d, J = 14.7 Hz, 1H), 5.04 (dd, J = 18.3, 15.4 Hz, 1H), 4.55 (dd, J = 9.5, 8.0 Hz, 1H),
4.10 (t, J = 9.5 Hz, 1H), 3.88-3.80 (m, 1H), 3.10 (q, J = 8.9 Hz, 1H), 1.32 (q, J = 8.9 Hz, 1H), 1.32 (s,
3H), 0.76 (d, J = 6.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 184.6, 175.5, 152.4, 137.5, 135.2, 129.3,
128.8, 128.7, 128.2, 127.9, 120.2, 116.9, 69.7, 57.5, 56.1, 50.6, 46.8, 46.3, 22.8, 15.2; HRMS(ES+) calcd
for C25H25Cl2N2O4 (M+H)+ 487.1191, found 487.1182.
5-Cyano-1,3-dibenzyl-4-formylimidazolidin-2-one (42). To a solution of 31 (1.00 g, 3.4
O
BnN
NC
NBn
mmol, 1.0 equiv) in trifluoroacetic acid (30 mL) was added bromine (0.53 mL, 10.2 mmol,
CHO
3.0 equiv). After stirring at 23 °C for 2 h, the solvent was removed by vacuum and the
residue was dissolved with methylene chloride (50 mL), washed with sodium thiosulfate (10% in
saturated aqueous sodium bicarbonate, 20 mL×3), dried over anhydrous sodium sulfate, filtered and
concentrated. The crude bromide obtained was dissolved in anhydrous N,N-dimethylformamide (20 mL)
and copper(I) cyanide (0.91 g, 10.2 mmol, 3.0 equiv) was added. After stirring at 120 °C for 12 h, the
reaction mixture was diluted with methylene chloride (100 mL) and washed with ammonium hydroxide
(10% in saturated aqueous ammonium chloride, 20 mL×4). The organic layer was evaporated and the
reidue was pruifeid by silica gel (Davisil 633) column chromatography to afford pure 42 (0.56 g, 52%)
as pale yellow oil: Rf = 0.67 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 2848, 1722, 1679, 1448,
1417, 1342, 1356, 1179, 1023, 882, 744, 700; 1H NMR (400 MHz, CDCl3) δ 9.56 (s, 1H), 7.44-7.25 (m,
10H), 5.26 (s, 2H), 5.01 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 176.0, 151.9, 136.4, 134.8, 129.7 ,129.5,
129.2, 128.9 128.8, 128.7, 128.5, 128.2, 108.9, 77.2, 47.6, 46.7; HRMS(ES+) calcd for C29H29N2O4
(M+H)+ 469.2127, found 469.2109.
NC
O
BnN
NBn
O
(E)-Cinnamyl
O
2-(tert-butoxycarbamoyl)methyl-3-(5-cyano-2,4-
O
dibenzylimidazolidin-3-onyl)-3-oxopropionate (23). Prepared as for 8
NHBoc
and obtained as pale yellow oil (80 mg, 52% over three steps): Rf = 0.70
(50% ethyl acetate-hexanes); FTIR (neat, cm–1) 1714, 1652, 1542, 1495, 1440, 1350, 1174, 967, 744,
698; 1H NMR (400 MHz, CDCl3) δ 7.43-7.26 (m, 15H), 6.58 (d, J = 15.8 Hz, 1H), 6.15-6.05 (m, 1H),
5.32 (d, J = 14.2 Hz, 1H), 5.23 (d, J = 14.7 Hz, 1H), 4.98 (s, 2H), 4.84 (br, 2H), 4.75-4.64 (m, 2H), 4.55
(m, 1H), 3.71-3.56 (m, 2H), 1.39 (s, 9H);
13
C NMR (75 MHz, CDCl3) δ 183.4, 167.6, 155.8, 151.9,
136.6, 136.1, 135.2, 134.8, 129.3, 129.0, 128.9, 128.8, 128.5, 128.3, 128.2, 127.0, 122.1, 110.4, 104.4,
80.1, 66.8, 55.1, 47.6, 47.1, 39.7, 28.5.
S14
Bn
N O
O
BnN
O
(5R*,1’S*,5’S*,6’S*)-Spiro{(1,3-dibenzylimidazolin-2,4-dione)-5,7’-(2’,8’dioxo-1’-(tert-butoxycarbamoyl)methyl-6’-methyl-3’-oxabicycle[3.3.0]octane)}
H
H
BocHN
O
(24). Prepared as for 7 by reacting 23 (10 mg) with manganese(III) acetate at 60
°C for 2 h to give 24 (5.8 mg, 60%) as pale yellow oil: Rf = 0.72 (50% ethyl
O
acetate-hexanes); FTIR (neat, cm–1); 2926, 1719, 1669, 1557, 1496, 1443, 1411, 1365, 1251, 1166, 1029,
966, 746; 1H NMR (400 MHz, CDCl3) δ 7.51-7.12(m, 9H), 7.03 (t, J = 7.5 Hz, 2H), 6.80 (d, J = 7.7 Hz,
2H), 6.60 (d, J = 7.7 Hz, 2H), 5.07-4.94 (m, 2H), 4.49 (d, J = 15.0 Hz, 1H, 4.44 (d, J = 15.4 Hz, 1H),
4.41-4.37 (m, 1H), 4.13-4.12 (m, 1H), 3.97-3.94 (m, 1H), 3.85-3.83 (m, 1H), 3.71 (dd, J = 11.7, 6.6 Hz,
1H), 3.08 (d, J = 11.7 Hz, 1H), 1.47 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 200.4, 170.0, 167.8, 156.6,
153.9, 136.3, 135.2, 134.9, 132.0, 129.8, 129.5, 129.3, 129.2, 129.1, 128.9, 128.8, 128.2, 127.8, 127.6,
127.4, 121.8, 80.3, 70.2, 65.3, 50.0, 47.7, 47.3, 45.7, 43.0, 42.9, 28.4; MS(ES+) C35H36N3O7 (M+Na)+
632.25.
O
BnN
mCPBA, CH2Cl2
H
O
Me
O
O
Bn
N O
O
NBn
H
7
23 °C, 7 d
96% yield
BnN
O
H
H
Me
O
O
15
To a solution of 7 (30.0 mg, 0.063 mmol, 1.0 equiv) in methylene chloride (5 mL) was added mchloroperbenzoic acid (21.6 mg, 0.125 mmol, 2.0 equiv). After stirring at 23 °C for 7 d, the reaction
was quenched with sodium thiosulfate (10% in saturated aqueous sodium bicarbonate, 10 mL), dried
over anhydrous sodium sulfate, filtered, concentrated and crystallized from diethyl ether to give pure 15
(29.6 mg, 96%) as white solid. Recrystallization from diethyl ester provided single crystals suitable for
X-ray analysis.
O
BnN
NBn
H
Cl
OTIPS
chloro-1-tri(iso-propyl)silyloxyethyl]-7,9-diaza-4hydroxymethylbicyclo[4.3.0]non-1(6)-ene (25) To a solution of 9 (35 mg, 0.047
O
BocHN
(3S,4S,5S)-3-(tert-butoxycarbamoyl)methyl-7,9-dibenzyl-2,8-dioxo-5-[(R)-2-
OH
mmol, 1.0 equiv) in tetrahydrofuran (0.5 mL) was added lithium hydroxide (0.33
N in water, 0.4 mL). After stirring at 50 °C for 15 min, the solvent was removed by vacuum and the
residue was dissolved with methylene chloride (5 mL). The organic layer was washed with saturated
ammonium chloride (2 mL), dried over anhydrous sodium sulfate, filtered and purified by silica gel
(Davisil 633) column chromatography to afford pure 25 (20 mg, 59 %): Rf = 0.58 (50% ethyl acetatehexanes): FTIR (neat, cm–1) 3381, 2928, 2870, 1629, 1640, 1495, 1330, 1252, 1072, 880, 700; 1H NMR
(400 MHz, CDCl3); 7.39-7.17 (m, 10H), 4.79-4.75 (m, 2H), 4.70 (d, J = 14.7 Hz, 1H), 4.53 (d, J = 14.6
S15
Hz, 1H), 4.42 (d, J = 14.2 Hz, 1H), 4.20 (d, J = 10.6 Hz, 1H), 3.90-3.86 (m, 2H), 3.40 (dd, J = 11.4, 7.0
Hz, 1H), 3.30-3.23 (m, 3H), 3.08-3.04 (m, 1H), 2.67-2.63 (m, 1H), 2.64-2.40 (m, 1H), 1.43 (s, 9H),
1.04-0.68 (m, 21H); 13C NMR (75 MHz, CDCl3) δ 209.8, 169.9, 158.1, 157.0,135.9, 135.6, 129.1, 128.9,
128.8, 128.7, 128.6, 128.4, 128.2, 128.0, 80.6, 80.4, 75.3, 71.2, 47.7, 47.4, 45.3, 43.7, 42.0, 32.2, 28.6,
18.5, 13.3 ; HRMS(ES+) calcd for C39H56ClN3NaO7Si (M+Na)+ 764.3474, found 764.3477.
Bn
N O
H
BnN
O
Cl
(5S*,3’S*,4’S*,5’R*)-Spiro{(1,3-dibenzylimidazolin-2,4-dione)-5,2’-(1’-oxo-5’(tert-butoxycarbamoyl)methyl-4’-hydroxymethyl-3’-[(R)-2-chloro-1-tri(iso-
OTIPS
O
OH
propyl)silyloxyethyl]bicycle[3.3.0]octane)} (26). To a solution of 25 (18.0 mg,
0.028 mmol, 1.0 equiv) in chloroform (2 mL) was added 3-chloroperbenzoic acid
NHBoc
(20.0 mg, 0.11 mmol, 4.0 equiv). After stirring for 16 h at 23 °C, the reaction was quenched with a
solution of sodium thiosulfate (1.0 M in saturated aqueous sodium bicarbonate, 2 mL). The layers were
separated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and
purified by silica gel (Davisil 633) column chromatography to afford pure 26 (13.9 mg, 78 %) as pale
yellow oil: Rf = 0.58 (50% ethyl acetate-hexanes): FTIR (neat, cm–1) 3381, 2928, 2870, 1629, 1640,
1495, 1330, 1252, 1072, 880, 700; 1H NMR (400 MHz, CDCl3) δ 7.39-7.17 (m, 10H), 4.79-4.75 (m, 2H),
4.70 (d, J = 14.7 Hz, 1H), 4.53 (d, J = 14.6 Hz, 1H), 4.42 (d, J = 14.2 Hz, 1H), 4.20 (d, J = 10.6 Hz, 1H),
3.90-3.86 (m, 2H), 3.40 (dd, J = 11.4, 7.0 Hz, 1H), 3.30-3.23 (m, 3H), 3.08-3.04 (m, 1H), 2.67-2.63 (m,
1H), 2.64-2.40 (m, 1H), 1.43 (s, 9H), 1.04-0.68 (m, 21H); 13C NMR (75 MHz, CDCl3) δ 209.8, 169.9,
158.1, 157.0,135.9, 135.6, 129.1, 128.9, 128.8, 128.7, 128.6, 128.4, 128.2, 128.0, 80.6, 80.4, 75.3, 71.2,
47.7, 47.4, 45.3, 43.7, 42.0, 32.2, 28.6, 18.5, 13.3; HRMS(ES+) calcd for C39H56ClN3NaO7Si (M+Na)+
764.3474, found 764.3477.
O
BnN
Cl
NBn
H
H
O
BocHN O
O
OH
(3R,7S,8S)-3-(tert-butoxycarbamoyl)methyl-10,12-dibenzyl-2,4,11-trioxo-8-[(R)2-chloro-1-hydroxyethyl]-10,12-diaza-5-oxa-tricyclo[7.3.0.03,7]dodec-1(9)-ene
(43). To a solution of 9 (25.1 mg, 0.033 mmol, 1.0 equiv) in methanol (2 mL) was
added ammonium fluoride (10 mg, 0.27 mmol, 8.0 equiv) followed by acetic acid
(0.01 ml, 0.165 mmol, 5.0 equiv). After stirring at 60 °C for 12 h, the solvent was removed by vacuum.
The residue was dissolved with methylene chloride (5 mL), washed with saturated aqueous sodium
bicarbonate (1 mL), brine (1 mL), dried over anhydrous sodium sulfate, filtered, concentrated and
purified by silica gel (Davisil 633) column chromatography to give pure 43 (16.5 mg, 83%) as pale
yellow oil: Rf = 0.37 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3306, 1777, 1698, 1650, 1463, 145
3, 1167, 733, 701; 1H NMR (400 MHz, CDCl3) δ 7.43-7.41 (m, 2H), 7.40-7.24 (m, 6H), 7.17-7.15 (m,
2H), 5.80 (d, J = 8.8 Hz, 1H), 5.42 (d, J = 15.8 Hz, 1H), 5.23 (s, 2H), 5.08 (dd, J = 8.8, 5.5 Hz, 1H),
S16
4.74 (d, J = 15.8 Hz, 1H), 4.08 (t, J = 8.9 Hz, 1H), 4.00-3.97 (m, 1H), 3.90 (dd, J = 14.9, 5.5 Hz, 1H),
3.80 (dd, J = 14.9, 9.0 Hz, 1H), 3.70 (dd, J = 11.3, 4.2 Hz, 1H), 3.62 (dd, J = 11.4, 8.1 Hz, 1H), 3.21 (dd,
J = 10.7, 9.0 Hz, 1H), 3.06 (t, J = 9.9 Hz, 1H), 2.98 (d, J = 3.7 Hz, 1H), 1.41 (s, 9H);
13
C NMR (100
MHz, CDCl3) δ 173.5, 172.4, 158.6, 154.2, 138.2, 137.3, 135.9, 129.4, 128.8, 128.7, 128.0, 127.2, 119.1,
82.3, 72.6, 68.8, 59.3, 46.3, 45.7, 45.4, 44.8, 35.8, 33.8, 28.4; HRMS(ES+) calcd for C31H35ClN3O7
(M+H)+ 596.2163, found 596.2153.
Bn
N O
O
BnN
O
Cl
(tert-butoxycarbamoyl)methyl-6’-[(R)-2-chloro-1-hydroxyethyl]-3’-oxa-
H
OH
H
BocHN
O
(5R,1’R,5’S,6’S)-Spiro{(1,3-dibenzylimidazolin-2,4-dione)-5,7’-(2’,8’-dioxo-1’bicycle[3.3.0]octane)} (27). To a solution of 43 (8.0 mg, 0.013 mmol, 1.0 equiv)
in chloroform (1 mL) was added 3-chloroperbenzoic acid (11.2 mg, 0.067 mmol,
O
5.0 equiv). After stirring for 16 h at 60 °C, the reaction was quenched with a solution of sodium
thiosulfate (1.0 M in saturated aqueous sodium bicarbonate, 0.5 mL). The layers were separated and the
organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and purified by silica gel
(Davisil 633) column chromatography to afford pure 27 (6.4 mg, 78 %) as pale yellow oil: Rf = 0.53
(50% ethyl acetate-hexanes). Rf = 0.53 (50% ethyl acetate-hexanes). FTIR (neat, cm–1) 3378, 2926, 1790,
1771, 1710, 1514, 1442, 1368, 1251, 1170, 1136, 910, 733, 701; 1H NMR (400 MHz, CDCl3) δ 7.407.16 (m, 10H), 5.03 (d, J = 15.2 Hz, 1H), 4.96-4.92 (m, 1H), 4.68 (dd, J = 17.3, 14.5 Hz, 2H), 4.45-4.36
(m, 2H), 3.81-3.78 (m, 3H), 3.65-3.58 (m, 2H), 2.80 (dd, J = 11.4, 2.4 Hz, 1H), 2.44 (t, J = 9.5 Hz, 1H),
2.39 (br, 1H), 1.88 (t, J = 9.5 Hz, 1H), 1.44 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 200.7, 169.9, 167.1,
156.4, 156.1, 135.3, 135.2, 129.7, 129.6, 129.3, 129.2, 128.7, 128.6, 128.4, 128.2, 80.8, 77.4, 72.9, 71.5,
64.4, 48.5, 46.5, 46.0, 43.6, 43.1, 38.3, 28.4; HRMS(ES+) calcd for C31H38ClN4O8 (M+NH4)+ 629.2378,
found 629.2372.
Bn
N O
H
BnN
(5R*,3’S*,4’S*,5’S*)-Spiro{(1,3-dibenzylimidazolin-2,4-dione)-5,2’-(1’-oxo-5’-
O
O
O
H
OH
NHBoc
(tert-butoxycarbamoyl)methyl-4’-hydroxymethyl-3’-(R)epoxybicycle[3.3.0]octane)} (28). Prepared as for 25 from 27 (10 mg) by reacting
with LiOH to give 28 as white solid (6.5 mg, 72 %): Rf = 0.10 (50% ethyl acetate-
hexanes); FTIR (neat, cm–1) 3380, 2927, 1790, 1755, 1516, 1423, 1169, 913, 733, 691; 1H NMR (400
MHz, CDCl3) δ 7.47-7.24 (m, 10H, 5.12 (d, J = 16.5 Hz, 1H), 4.86 (d, J = 14.3 Hz, 1H), 4.80-4.65 (m,
2H), 3.77 (d, J = 6.9 Hz, 2H), 3.68 (t, J = 9.2 Hz, 1H), 3.10-3.04 (m, 1H), 2.81-2.71 (m, 2H), 1.83 (d, J
= 7.5 Hz, 1H), 1.64 (t, J = 8.8 Hz, 1H), 1.46 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 177.3, 171.8, 157.6,
156.0, 137.1, 136.0, 129.5, 129.0, 128.4, 128.3, 127.1, 79.8, 76.8, 70.1, 59.3, 49.8, 45.7, 43.5, 38.4, 34.5,
33.1, 32.2, 28.6; HRMS(ES+) calcd for C30H35N3NaO7 (M+Na)+ 572.2373, found 572.2359.
S17
O
BnN
Cl
NBn
H
H
O
chloro-1-oxoethyl]-10,12-diaza-5-oxa-tricyclo[7.3.0.03,7]dodec-1(9)-ene (29). To a
solution of 43 (15.1 mg, 0.025 mmol, 1.0 equiv) in anhydous methylene chloride (2
O
BocHN O
(3R,7S,8S)-3-(tert-butoxycarbamoyl)methyl-10,12-dibenzyl-2,4,11-trioxo-8-[2-
mL) was added Dess-Martin periodinane (21.0 mg, 0.05 mmol, 2.0 equiv). After
O
stirring for 3 h at 45 °C, the reaction was quenched with a solution of sodium thiosulfate (1.0 N in
saturated aqueous sodium bicarbonate, 1 mL). The layers were separated and the organic layer was
washed with saturated aqueous sodium bicarbonate (0.5 mL), brine (0.5 mL), dried over anhydrous
sodium sulfate, filtered and concentrated and purified by silica gel (Davisil 633) column
chromatography to afford pure 29 (15.0 mg, 99%) as pale yellow oil: [α]D27 –132° (c 0.10, CHCl3); Rf =
0.35 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 1781, 1711, 1650, 1468, 1165, 1027, 732, 701; 1H
NMR (400 MHz, CDCl3) δ 7.42 (d, J = 6.8 Hz, 2H), 7.36-7.26 (m, 6H), 7.17-7.15 (m, 2H), 5.30 (d, J =
14.7 Hz, 1H), 5.24 (d, J = 14.8 Hz, 1H), 5.08 (d, J = 15.9 Hz, 1H), 4.87-4.84 (m, 1H), 4.61 (t, J = 15.7
Hz, 1H), 4.35 (t, J = 8.6 Hz, 1H), 4.15 (s, 1H), 3.73 (d, J = 15.8 Hz, 1H), 3.60-3.53 (m, 2H), 3.41-3.30
(m, 2H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 198.4, 173.7, 171.5, 156.9, 153.8, 137.2, 135.1,
134.4, 129.6, 129.0, 128.9, 128.7, 128.6, 128.0, 127.6, 119.7, 80.8, 68.4, 59.4, 47.2, 46.4, 45.8, 43.8,
40.2, 35.5, 28.4; HRMS(ES+) calcd for C31H32ClN3O7 (M+H)+ 596.2163, found 596.2153.
O
BnN
Cl
NBn
H
H
O
BocHN O
O
OH
(3S,7R,8R)-3-(tert-butoxycarbamoyl)methyl-10,12-dibenzyl-2,4,11-trioxo-8-[(R)2-chloro-1-hydroxyethyl]-10,12-diaza-5-oxa-tricyclo[7.3.0.03,7]dodec-1(9)-ene
(44). To a solution of 10 (24.9 mg, 0.033 mmol, 1.0 equiv) in methanol (2 mL) was
added ammonium fluoride (10.0 mg, 0.27 mmol, 8.0 equiv) followed by acetic acid
(0.01 mL, 0.165 mmol, 5.0 equiv). After stirring at 60 °C for 48 h, the solvent was removed by vacuum.
The residue was dissolved with methylene chloride (5 mL), washed with saturated aqueous sodium
bicarbonate (1 mL), brine (1 mL), dried over anhydrous sodium sulfate, filtered, concentrated and
purified by silica gel (Davisil 633) column chromatography to give pure 44 (16.1 mg, 81%) as pale
yellow oil: Rf = 0.39 (50% ethyl acetate-hexanes); FTIR (neat, cm–1) 3368, 2978, 1779, 1704, 1469,
1169, 1064, 910, 733, 701; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 7.0 Hz, 2H), 7.31-7.24 (m, 6H),
7.15-7.13 (m, 2H), 5.48 (d, J = 15.6 Hz, 1H), 5.22 (s, 2H), 4.88-4.83 (m, 2H), 4.20-4.17 (m, 1H), 4.00 (t,
J = 8.9 Hz, 1H), 3.87 (dd, J = 14.7, 5.2 Hz, 1H), 3.80-3.72 (m, 2H), 3.67 (dd, J = 11.9, 5.9 Hz, 1H), 3.06
(t, J = 9.8 Hz, 1H), 2.94 (d, J = 6.0 Hz, 1H), 2.83 (d, J = 9.8 Hz, 1H), 1.40 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 173.9, 172.5, 157.5, 154.3, 137.5, 137.4, 136.6, 129.3, 128.8, 128.6, 128.0, 127.4, 119.3, 81.3,
73.4, 68.5, 59.3, 47.4, 46.3, 46.1, 45.4, 37.5, 35.1, 28.4; HRMS(ES+) calcd for C31H35ClN3O7 (M+H)+
596.2163, found 596.2161.
S18
O
BnN
Cl
NBn
H
H
O
BocHN O
1
O
O
(3S,7R,8R)-3-(tert-butoxycarbamoyl)methyl-10,12-dibenzyl-2,4,11-trioxo-8-[2chloro-1-oxoethyl]-10,12-diaza-5-oxa-tricyclo[7.3.0.03,7]dodec-1(9)-ene
(30=ent-
29). Prepared as for 29 from 44 and obtained as pale yellow oil (15.1 mg, 96%):
[α]D27 +131° (c 0.07, CHCl3); Rf = 0.35 (50% ethyl acetate-hexanes); FTIR (neat, cm–
) 1781, 1711, 1650, 1468, 1165, 1027, 732, 701; 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 6.8 Hz, 2H),
7.36-7.26 (m, 6H), 7.17-7.15 (m, 2H), 5.30 (d, J = 14.7 Hz, 1H), 5.24 (d, J = 14.8 Hz, 1H), 5.08 (d, J =
15.9 Hz, 1H), 4.87-4.84 (m, 1H), 4.61 (t, J = 15.7 Hz, 1H), 4.35 (t, J = 8.6 Hz, 1H), 4.15 (s, 1H), 3.73 (d,
J = 15.8 Hz, 1H), 3.60-3.53 (m, 2H), 3.41-3.30 (m, 2H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
198.4, 173.7, 171.5, 156.9, 153.8, 137.2, 135.1, 134.4, 129.6, 129.0, 128.9, 128.7, 128.6, 128.0, 127.6,
119.7, 80.8, 68.4, 59.4, 47.2, 46.4, 45.8, 43.8, 40.2, 35.5, 28.4; HRMS(ES+) calcd for C31H32ClN3O7
(M+H)+ 596.2163, found 596.2155.
S19
The crystals were grown by slow evaporation of 15 from diethyl ether. X-ray data was collected on
kappaCCD X-ray diffractometer at room temperature. The diffraction pattern was collected using
COLLECT software of Bruker-axs Inc. It was indexed and scaled using HKL2000 (Z. Otwinowski, W.
Minor, Methods Enzymol. 1997, 276 (Macromolecular Crystallography Part A.) 307–326). The crystals
are monoclinic with space group P21/n. The crystal data and refinement parameters are listed in Table
S1. The structure was solved using the direct-methods SHELXS-97 and refined with SHELXL-97 (G.
M. Sheldrick, (1997) SHELXS-97 and SHELXL-97 University of Gottingen, Germany). One molecule
(Figure S2) is presented in the asymmetric unit. There are four molecules in the unit cell. The
coordinates of all the non-hydrogen atoms are presented in Table S2. The bond lengths and angles are
given in Table S3. Table S4 gives the anisotropic thermal parameters and Table S5 has the hydrogen
atom coordinates. The drawing was done at 50% ellipsoids.
Figure S2
S20
Table S1.
Crystal data and structure refinement for shelxl.
Identification code
shelxl
Empirical formula
C30 H26 N2 O5
Formula weight
494.1842
Temperature
293(2) K
Wavelength
0.71073 A
Crystal system, space group
monoclinic, P21/n
Unit cell dimensions
a = 9.7490(3) Å
b = 18.4670(5) Å
c = 14.4930(5) Å
Volume
2524.37(14) A^3
Z, Calculated density
4,
Absorption coefficient
0.182 mm^-1
F(000)
972
Crystal size
0.5 x 0.3 x 0.2 mm
Theta range for data collection
2.89 to 21.96 deg.
Limiting indices
0<=h<=10, 0<=k<=19, -15<=l<=14
Reflections collected / unique
2901 / 2901 [R(int) = 0.0000]
Completeness to theta = 21.96
93.9 %
Refinement method
Full-matrix least-squares on F^2
Data / restraints / parameters
2901 / 0 / 438
Goodness-of-fit on F^2
1.039
Final R indices [I>2sigma(I)]
R1 = 0.0620, wR2 = 0.1511
R indices (all data)
R1 = 0.0914, wR2 = 0.1681
Largest diff. peak and hole
0.149 and -0.156 e.A^-3
S21
alpha = 90 °.
beta = 104.65(3)°
gamma = 90°.
1.195 Mg/m^3
Table S2.
Atomic coordinates ( x 10^4) and equivalent isotropic
displacement parameters (A^2 x 10^3) for shelxl.
U(eq) is defined as one third of the trace of the orthogonalized
Uij tensor.
________________________________________________________________
x
y
z
U(eq)
________________________________________________________________
O(1)
3718(3)
355(1)
1690(2)
69(1)
N(002)
1852(3)
1164(1)
1379(2)
54(1)
N(003)
1550(3)
79(1)
1964(2)
53(1)
C(004)
2513(4)
503(2)
1686(2)
53(1)
C(005)
-422(3)
531(2)
2682(2)
54(1)
O(6)
-3460(3)
-1011(2)
1141(2)
82(1)
C(007)
-1020(4)
14(2)
1107(3)
56(1)
O(8)
-3213(3)
-432(2)
2514(2)
86(1)
O(9)
-425(3)
1613(1)
1044(2)
72(1)
O(10)
-866(3)
-404(1)
514(2)
74(1)
C(011)
3789(4)
2053(2)
1788(3)
60(1)
C(012)
183(3)
427(2)
1800(2)
50(1)
C(013)
-2025(4)
637(2)
2262(3)
62(1)
C(014)
453(4)
1147(2)
1354(2)
55(1)
C(015)
305(4)
1096(2)
3403(3)
63(1)
C(016)
5066(4)
2215(2)
1582(4)
76(1)
C(017)
2607(5)
1743(2)
1022(3)
68(1)
C(018)
-2423(3)
203(2)
1338(2)
57(1)
C(019)
-3090(4)
-487(2)
1618(3)
65(1)
C(020)
2381(4)
-850(2)
3224(3)
66(1)
C(021)
3636(5)
2211(2)
2683(3)
74(1)
C(022)
1827(5)
-689(2)
2184(3)
65(1)
C(023)
-3439(5)
562(3)
481(3)
69(1)
C(024)
3(4)
1829(2)
3279(3)
73(1)
C(025)
1509(7)
-1140(2)
3734(4)
89(1)
S22
C(026)
-2927(6)
296(3)
2863(4)
88(2)
C(027)
1307(4)
880(3)
4208(3)
82(1)
C(028)
711(5)
2332(3)
3947(4)
87(1)
C(029)
5965(6)
2691(3)
3148(5)
96(2)
C(030)
1712(6)
2110(4)
4736(4)
103(2)
C(031)
4707(6)
2526(2)
3367(4)
84(1)
C(032)
2057(15)
-1290(3)
4694(6)
129(3)
C(033)
6140(5)
2541(2)
2264(5)
91(2)
C(034)
1997(5)
1392(4)
4870(4)
109(2)
C(035)
3411(15)
-1165(5)
5128(6)
151(4)
C(036)
3758(6)
-721(4)
3682(4)
121(2)
C(039)
4264(10)
-861(6)
4637(6)
179(4)
________________________________________________________________
S23
Table S3.
Bond lengths [A] and angles [deg] for shelxl.
_____________________________________________________________
O(1)-C(004)
1.204(4)
N(002)-C(014)
1.355(4)
N(002)-C(004)
1.400(4)
N(002)-C(017)
1.464(4)
N(003)-C(004)
1.360(4)
N(003)-C(012)
1.444(4)
N(003)-C(022)
1.463(5)
C(005)-C(015)
1.520(5)
C(005)-C(013)
1.540(5)
C(005)-C(012)
1.549(5)
O(6)-C(019)
1.192(4)
C(007)-O(10)
1.193(4)
C(007)-C(018)
1.528(5)
C(007)-C(012)
1.539(5)
O(8)-C(019)
1.338(5)
O(8)-C(026)
1.439(5)
O(9)-C(014)
1.217(4)
C(011)-C(021)
1.374(5)
C(011)-C(016)
1.384(5)
C(011)-C(017)
1.496(5)
C(012)-C(014)
1.531(5)
C(013)-C(018)
1.526(5)
C(013)-C(026)
1.522(6)
C(015)-C(027)
1.377(5)
C(015)-C(024)
1.388(5)
C(016)-C(033)
1.383(7)
C(018)-C(023)
1.530(5)
C(018)-C(019)
1.531(5)
C(020)-C(036)
1.360(7)
S24
C(020)-C(025)
1.369(6)
C(020)-C(022)
1.496(6)
C(021)-C(031)
1.375(6)
C(024)-C(028)
1.391(6)
C(025)-C(032)
1.386(9)
C(027)-C(034)
1.393(6)
C(028)-C(030)
1.364(7)
C(029)-C(033)
1.363(7)
C(029)-C(031)
1.377(7)
C(030)-C(034)
1.360(8)
C(032)-C(035)
1.331(12)
C(035)-C(039)
1.347(13)
C(036)-C(039)
1.371(10)
C(014)-N(002)-C(004)
111.6(3)
C(014)-N(002)-C(017)
126.8(3)
C(004)-N(002)-C(017)
121.1(3)
C(004)-N(003)-C(012)
111.9(3)
C(004)-N(003)-C(022)
121.3(3)
C(012)-N(003)-C(022)
125.4(3)
O(1)-C(004)-N(003)
127.9(3)
O(1)-C(004)-N(002)
124.7(3)
N(003)-C(004)-N(002)
107.4(3)
C(015)-C(005)-C(013)
115.7(3)
C(015)-C(005)-C(012)
116.4(3)
C(013)-C(005)-C(012)
104.5(3)
O(10)-C(007)-C(018)
126.0(3)
O(10)-C(007)-C(012)
125.2(3)
C(018)-C(007)-C(012)
108.7(3)
C(019)-O(8)-C(026)
110.8(3)
C(021)-C(011)-C(016)
118.4(4)
C(021)-C(011)-C(017)
122.3(4)
S25
C(016)-C(011)-C(017)
119.3(4)
N(003)-C(012)-C(014)
101.9(3)
N(003)-C(012)-C(007)
113.9(3)
C(014)-C(012)-C(007)
109.8(3)
N(003)-C(012)-C(005)
116.6(3)
C(014)-C(012)-C(005)
112.6(3)
C(007)-C(012)-C(005)
102.3(3)
C(018)-C(013)-C(026)
103.3(3)
C(018)-C(013)-C(005)
106.7(3)
C(026)-C(013)-C(005)
113.4(4)
O(9)-C(014)-N(002)
127.1(3)
O(9)-C(014)-C(012)
126.1(3)
N(002)-C(014)-C(012)
106.8(3)
C(027)-C(015)-C(024)
118.3(4)
C(027)-C(015)-C(005)
119.4(4)
C(024)-C(015)-C(005)
122.3(4)
C(011)-C(016)-C(033)
120.0(5)
N(002)-C(017)-C(011)
112.2(3)
C(013)-C(018)-C(007)
105.6(3)
C(013)-C(018)-C(023)
117.0(3)
C(007)-C(018)-C(023)
110.7(3)
C(013)-C(018)-C(019)
103.6(3)
C(007)-C(018)-C(019)
109.4(3)
C(023)-C(018)-C(019)
110.1(3)
O(6)-C(019)-O(8)
122.4(4)
O(6)-C(019)-C(018)
127.5(4)
O(8)-C(019)-C(018)
110.1(4)
C(036)-C(020)-C(025)
118.4(5)
C(036)-C(020)-C(022)
121.1(4)
C(025)-C(020)-C(022)
120.4(4)
C(031)-C(021)-C(011)
121.8(5)
S26
N(003)-C(022)-C(020)
114.3(3)
C(015)-C(024)-C(028)
120.6(5)
C(020)-C(025)-C(032)
119.1(7)
O(8)-C(026)-C(013)
105.9(3)
C(015)-C(027)-C(034)
120.2(5)
C(030)-C(028)-C(024)
120.4(5)
C(033)-C(029)-C(031)
120.2(5)
C(028)-C(030)-C(034)
119.3(5)
C(021)-C(031)-C(029)
119.0(5)
C(035)-C(032)-C(025)
121.6(8)
C(029)-C(033)-C(016)
120.5(5)
C(030)-C(034)-C(027)
121.2(5)
C(032)-C(035)-C(039)
119.6(8)
C(039)-C(036)-C(020)
121.2(7)
C(035)-C(039)-C(036)
120.0(8)
_____________________________________________________________
S27
Table S4.
Anisotropic displacement parameters (A^2 x 10^3) for shelxl.
The anisotropic displacement factor exponent takes the form:
-2 pi^2 [ h^2 a*^2 U11 + ... + 2 h k a* b* U12 ]
_______________________________________________________________________
U11
U22
U33
U23
U13
U12
_______________________________________________________________________
O(1)
51(2)
80(2)
81(2)
-2(1)
27(1)
2(1)
N(002)
53(2)
52(2)
58(2)
-1(1)
16(1)
-7(1)
N(003)
50(2)
47(2)
66(2)
1(1)
21(1)
-2(1)
C(004)
49(2)
60(2)
52(2)
-4(2)
15(2)
-2(2)
C(005)
44(2)
62(2)
56(2)
-6(2)
14(2)
-2(2)
O(6)
73(2)
66(2)
106(2)
-6(2)
24(2)
-10(1)
C(007)
58(2)
59(2)
54(2)
-6(2)
17(2)
-6(2)
O(8)
68(2)
114(3)
81(2)
-2(2)
28(2)
-20(2)
O(9)
64(2)
65(2)
83(2)
7(1)
12(1)
7(1)
O(10)
66(2)
86(2)
71(2)
-26(2)
24(1)
-13(1)
C(011)
62(3)
53(2)
66(3)
4(2)
19(2)
-9(2)
C(012)
44(2)
53(2)
54(2)
-5(2)
14(2)
0(2)
C(013)
51(3)
71(3)
66(3)
-13(2)
17(2)
-2(2)
C(014)
53(3)
56(2)
54(2)
-7(2)
9(2)
-1(2)
C(015)
54(2)
76(3)
62(3)
-16(2)
22(2)
0(2)
C(016)
71(3)
63(3)
97(4)
1(2)
27(3)
-4(2)
C(017)
71(3)
62(3)
73(3)
10(2)
23(2)
-11(2)
C(018)
46(2)
65(2)
59(2)
-9(2)
14(2)
-6(2)
C(019)
42(2)
80(3)
73(3)
2(2)
14(2)
1(2)
C(020)
63(3)
57(2)
80(3)
3(2)
22(2)
14(2)
C(021)
77(3)
72(3)
71(3)
1(2)
14(3)
-19(2)
C(022)
69(3)
53(3)
76(3)
-1(2)
25(2)
3(2)
C(023)
65(3)
70(3)
69(3)
-4(2)
13(2)
-1(2)
C(024)
68(3)
80(3)
73(3)
-20(2)
20(2)
-4(2)
C(025)
136(5)
59(3)
88(4)
-1(2)
54(3)
-14(3)
S28
C(026)
55(3)
136(5)
78(4)
-28(3)
24(3)
-12(3)
C(027)
66(3)
100(4)
72(3)
-27(3)
4(2)
15(2)
C(028)
80(3)
89(4)
97(4)
-34(3)
33(3)
-7(3)
C(029)
97(4)
65(3)
104(5)
12(3)
-17(4)
-15(3)
C(030)
73(3)
127(5)
108(4)
-62(4)
23(3)
-10(3)
C(031)
96(4)
71(3)
80(4)
4(2)
10(3)
-15(3)
C(032)
250(10)
63(3)
100(6)
15(3)
93(7)
5(5)
C(033)
61(3)
72(3)
135(5)
14(3)
16(3)
-10(2)
C(034)
77(4)
143(5)
91(4)
-56(4)
-7(3)
19(3)
C(035)
223(11)
138(6)
85(6)
9(5)
22(7)
100(7)
C(036)
68(4)
195(6)
98(4)
27(4)
18(3)
22(3)
C(039) 115(6)
314(12)
96(6)
14(6)
4(5)
90(7)
_______________________________________________________________________
S29
Table S5.
Hydrogen coordinates ( x 10^4) and isotropic
displacement parameters (A^2 x 10^3) for shelxl.
________________________________________________________________
x
y
z
U(eq)
________________________________________________________________
H(1)
2790(60)
1270(30)
5390(40)
127(18)
H(2)
-2270(40)
1120(20)
2140(30)
72(12)
H(3)
1470(50)
350(20)
4330(30)
105(16)
H(4)
5180(80)
-950(40)
5020(50)
200(30)
H(5)
1950(40)
2090(20)
850(30)
74(13)
H(6)
2280(50)
2490(30)
5160(40)
130(17)
H(7)
480(60)
-1320(30)
3330(40)
150(20)
H(8)
6670(50)
2950(20)
3620(30)
99(14)
H(9)
3770(70)
-1250(40)
5790(50)
180(30)
H(10)
1460(50)
-1500(30)
4890(30)
87(17)
H(11)
-250(30)
56(18)
3030(20)
56(9)
H(12)
-4290(40)
693(18)
650(20)
67(11)
H(13)
-640(40)
1982(19)
2650(30)
74(11)
H(14)
5100(40)
2070(20)
950(30)
78(13)
H(15)
-3550(40)
230(20)
-60(30)
86(13)
H(16)
850(40)
-950(20)
1890(20)
78(11)
H(17)
4500(50)
2650(20)
3950(30)
108(18)
H(18)
-2970(40)
1030(20)
330(30)
78(11)
H(19)
470(50)
2830(30)
3850(40)
126(19)
H(20)
-3760(50)
540(20)
2780(30)
84(14)
H(21)
2490(40)
-830(20)
1850(30)
75(12)
H(22)
2720(40)
2087(17)
2790(20)
57(10)
H(23)
4430(60)
-450(20)
3400(40)
114(17)
H(24)
6950(60)
2660(20)
2020(30)
112(17)
H(25)
3030(40)
1530(20)
440(30)
89(12)
H(26)
-2450(40)
240(20)
3570(30)
89(13)
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