Molecules 2019, 24, 3477
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3.4. (5S,5aR,8S,8aS,13bR,14S)-8-((tert-butyldimethylsilyl)oxy)-5a-hydroxy-10,14-dimethoxy-
1,2,5,5a,6,7,8,8a-octahydro-5,13-methanobenzo[2,3]benzofuro[4,3a-c]azepin-3(4H)-one (epi-15)
To as stirred solution of hemiketal 17 (10 mg, 0.02 mmol) in MeOH (1.0 mL) at 0 ◦C was added
NaBH4 (10 mg, 0.26 mmol). The reaction mixture was stirred at this temperature of 15 min, then it
was diluted with acetone (1.0 mL), water (1.0 mL), and Et2O (5 mL). The layers were separated and
the aqueous phase was further extracted with Et2O (2
washed with brine, dried over anhydrous MgSO4, filtered and concentrated to afford a crude solid
product (7 mg, 72.5% yield). Comparison of 1HNMR data for 15 and epi-15 clearly indicated their
×
5 mL). The combined organic extracts were
relationship as epimeric compounds.
1
epi-15: H NMR (300 MHz, CDCl3)
δ 6.95 (d, J = 8.4 Hz, 1H), 6.88(d, J = 8.4 Hz, 1H), 6.62 (br s,
1H), 4.88 (s, 1H), 4.43 (d, J = 6.6 Hz, 1H), 3.89 (s, 3H), 3.43–3.49 (m, 1H), 2.97 (d, J = 17.4 Hz, 1H), 2.43
(d, J = 17.4 Hz, 1H), 1.74–2.04 (m, 1H), 1.52–1.65 (m, 3H), 0.90 (s, 9H), 0.10 (s, 3H), 0.00 (s, 3H) ppm.
3.5. (4bR,5S,6S,8aR,9S,10R)-9-azido-6-((tert-butyldimethylsilyl)oxy)-4,5-epoxy3-methoxy-12-oxo-
5,6,7,8,9,10-hexahydro-8a,4b-(epoxyethano)phenanthren-10-yl nitrate (14)
To a stirred solution of lactone 3 [17b] (50 mg, 0.12 mmol) in AcN (5 mL) at 0 ◦C was added NaN3
(50 mg, 0.77 mmol) followed by CAN (220 mg, 0.40 mmol). After 30 min, the reaction mixture was
diluted with Et2O/satd. NaHCO3 (10 mL/5 mL). The layers were separated and the aqueous layer
was further extracted with Et2O (2
×
10 mL). The organic layers were combined, dried over MgSO4,
filtered and concentrated to afford a residue that was used as crude in the next step. A small sample of
azido nitrate 14 was subjected to purification by preparative TLC (SiO2 gel, 2:1 hex/EtOAc as eluent)
for characterization purposes. It was found to have limited stability.
14
:
[α]2D0
=
−
35.8 (c = 0.6, CH2Cl2); Rf = 0.44 (4:1; hexanes/EtOAc); IR (film) v 3434, 2955, 2929,
6.99 (d, J = 8.4 Hz,
2855, 2116, 1796, 1645, 1508, 1440, 1274, 837 cm−1; 1H NMR (300 MHz, CDCl3)
δ
1H), 6.96 (d, J = 8.4 Hz, 1H), 6.30 (d, J = 1.8 Hz, 1H), 4.40 (d, J = 7.8 Hz, 1H), 4.10 (d, J = 1.8 Hz, 1H),
3.95 (s, 3H), 3.25–3.29 (m, 1H), 3.04 (d, J = 17.7 Hz, 1H), 2.94 (d, J = 17.7 Hz, 1H), 2.13–2.17 (m, 1H),
1.68–1.77 (m, 3H), 0.89 (s, 9H), 0.10 (s, 3H), 0.00 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3)
δ
173.6, 151.8,
146.2, 128.9, 122.6, 116.5, 115.3, 99.4, 82.9, 80.5, 69.8, 67.5, 56.8, 49.6, 43.4, 29.7, 28.7, 26.7, 25.7, 18.0, 4.8,
5.2 ppm; MS (EI) m/z (%) 416(15), 386(60), 358(100), 328(30), 288(75), 272(45); HRMS (EI) calcd for
−
−
C19H21O8N4Si [M − C4H9-H2O], 461.1123 found 461.1118.
3.6. (4bR,5S,6S,8aR,9S,10S)-9-azido-6-((tert-butyldimethylsilyl)oxy)4,5-epoxy-3-methoxy-12-oxo-
5,6,7,8,9,10-hexahydro-8a,4b-(epoxyethano)phenanthren-10-yl acetate (2)
To the crude azido nitrate 14 (obtained from the previous step) dissolved in HOAc (1.5 mL)
◦
was added NaOAc (150 mg, 1.83 mmol) and the reaction mixture was heated to 100 C for 2 h.
After cooling to room temperature, the mixture was carefully diluted with satd NaHCO3/EtOAc
(
(
5 mL/5 mL). The layers were separated and the aqueous phase was further extracted with EtOAc
2 × 5 mL). The combined organic extracts were washed with brine, dried over anhydrous MgSO4,
filtered and concentrated to afford a residue that was subjected to chromatography on silica gel using
hexanes/EtOAc (2:1) as eluent to afford the product 2 as an oil (52 mg, 84% yield over two steps).
2:
[α]2D0
=
−
2.4 (c = 1.0, CH2Cl2); Rf = 0.50 (2:1; hexanes/EtOAc); IR (film) v 2954, 2928, 2855, 2113,
1796, 1747, 1632, 1507, 1441, 1264, 1125, 838, 738 cm−1; 1H NMR (300 MHz, CDCl3)
δ
6.92 (d, J = 8.4 Hz,
1H), 6.87 (d, J = 8.4 Hz, 1H), 6.20 (d, J = 2.7 Hz, 1H), 4.42 (d, J = 7.8 Hz, 1H), 3.94 (s, 3H), 3.90 (d, J = 2.7
Hz, 1H), 3.28–3.36 (m, 1H), 3.13 (d, J = 17.7 Hz, 1H), 3.04 (d, J = 17.7 Hz, 1H), 2.19–2.25 (m, 1H), 2.12 (s,
3H), 1.66–1.79 (m, 3H), 0.90 (s, 9H), 0.12 (s, 3H), 0.02 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3)
δ
173.9,
169.9, 145.8, 145.7, 127.8, 121.4, 120.4, 116.3, 99.3, 83.5, 71.3, 70.3, 69.1, 56.8, 49.8, 43.7, 29.7, 29.3, 26.8,
25.7, 21.1, 18.0, 4.7, 5.2 ppm; MS (EI) m/z (%) 458(80), 430(20), 398(40), 370(100), 343(40), 328(80),
300(45), 254(45), 117(90); HRMS (EI) calcd for C21H24O7N3Si [M − C4H9], 458.1378 found 458.1373.
−
−