PAPER
Synthesis of Polycyclic b-Lactams from D-Glucose Derived Chiral Template
2973
J = 3.2 Hz, 1 H, H-8), 6.04–6.10 (m, 1 H, H-13), 6.51 (d, J = 15.6
Hz, 1 H, H-14), 7.16–7.29 (m, 10 H, aromatic).
13C NMR (CDCl3, 125.76 MHz): d = 19.6, 26.7, 43.3, 56.5, 73.3,
80.5, 81.6, 81.7, 103.5, 112.2, 122.9, 126.6, 127.8, 128.0, 128.5,
128.6, 134.1, 136.2, 137.2, 167.5.
1H NMR (CDCl3, 200 MHz): d = 1.40 (s, 3 H, CH3), 1.53 (s, 3 H,
CH3), 2.27–2.40 (m, 1 H, H-13), 2.52–2.81 (m, 4 H, H-6, H-12, H-
14), 3.45 (dd, J = 5.4, 13.3 Hz, 1 H, H-12), 3.65 (t, J = 4.3 Hz, 1 H,
H-4), 4.71 (s, 2 H, PhCH2O), 4.67–4.80 (m, 3 H, H-3, H-5, H-7),
5.92 (d, J = 4.3 Hz, 1 H, H-8), 7.14–7.38 (m, 10 H, aromatic).
13C NMR (CDCl3, 50.32 MHz): d = 27.1, 27.5, 35.7, 37.3, 38.8,
47.5, 54.4, 72.6, 72.7, 81.8, 82.1, 105.5, 112.9, 126.6, 128.1, 128.4,
128.6, 129.0, 136.4, 138.5, 166.9.
MS: m/z = 562 [M + 1].
Anal. Calcd for C26H28NO5I: C, 55.62; H, 5.03; N, 2.49. Found: C,
55.43; H, 5.25; N, 2.56.
MS: m/z = 437 [M+].
Compound 23b
Anal. Calcd for C26H24NO5: C, 71.70; H, 6.71; N, 3.22. Found: C,
71.89; H, 6.85; N, 3.40.
White solid; mp 142–143 °C; [a]D25 +20.8 (c = 0.62, CHCl3).
IR (CHCl3): 1754 cm–1.
Radical Cyclization of 23a
1H NMR (200 MHz, CDCl3): d = 1.36 (s, 3 H, CH3), 1.53 (s, 3 H,
CH3), 3.87–4.00 (m, 2 H, H-6, H-12), 4.05 (t, J = 4.3 Hz, 1 H, H-4),
4.26 (dd, J = 5.8, 15.8 Hz, 1 H, H-12), 4.42–4.53 (m, 2 H, H-5, H-
7), 4.73–4.81 (m, 2 H, PhCHaHbO, H-3), 4.95 (d, J = 11.8 Hz, 1 H,
PhCHaHbO), 5.80 (d, J = 3.5 Hz, 1 H, H-8), 6.03–6.18 (m, 1 H, H-
13), 6.55 (d, J = 15.8 Hz, 1 H, H-14), 7.27–7.40 (m, 10 H, aromatic).
According to the general procedure the radical cyclization of b-lac-
tam 23a (0.175 g, 0.32 mmol) and purification by column chroma-
tography gave 25a (86 mg, 64%). It was found to be a
diastereomeric mixture (42:58) by 1H NMR spectrum.
Compound 25a
13C NMR (CDCl3, 125.76 MHz): d = 21.9, 26.5, 26.6, 43.9, 56.6,
73.1, 79.4, 80.7, 81.5, 103.4, 111.9, 123.0, 126.4, 127.8, 128.1,
128.3, 128.7, 134.3, 136.1, 137.1, 167.3.
White crystalline solid; mp 165–166 °C.
IR (CHCl3): 1763 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.28 (s, 3 H, CH3), 1.29 (s, 3 H,
CH3), 1.32 (s, 3 H, CH3), 1.39 (s, 3 H, CH3), 2.04 (dd, J = 2.8, 11.0
Hz, 1 H, H-13), 2.28–2.30 (m, 1 H, H-13), 2.32–2.64 (m, 4 H, H-6,
H-14), 2.75–2.95 (m, 2 H, H-14), 3.06 (d, J = 8.0 Hz, 2 H, H-12),
3.66–3.86 (m, 3 H, H-12, H-4), 4.23 (t, J = 3.9 Hz, 1 H, H-4), 4.53
(d, J = 3.5 Hz, 1 H, H-5), 4.60 (d, J = 5.8 Hz, 1 H, H-5), 4.76 (d,
J = 3.9 Hz, 1 H, H-3), 5.30 (d, J = 3.9 Hz, 1 H, H-3), 5.39 (d, J = 3.9
Hz, 1 H, H-7), 5.86 (d, J = 3.5 Hz, 1 H, H-7), 5.93 (d, J = 3.5 Hz, 1
H, H-8), 5.93 (d, J = 3.5 Hz, 1 H, H-8), 6.99–7.32 (m, aromatic).
13C NMR (CDCl3, 50.32 MHz): d = 26.1, 26.4, 26.9, 32.9, 34.8,
36.5, 38.3, 40.2, 40.5, 47.0, 48.0, 52.9, 70.9, 73.9, 79.5, 80.8, 81.5,
82.1, 104.9, 105.5, 111.2, 115.5, 115.6, 122.0, 126.7, 128.6, 128.7
128.9, 129.3, 137.5, 138.6, 157.5, 157.6, 163.9, 168.2.
MS: m/z = 562 [M + 1].
Anal. Calcd for C26H28NO5I: C. 55.62; H, 5.03; N, 2.49. Found: C,
55.48; H, 5.22; N, 2.68.
Radical Cyclization of N-Cinnamyl-b-lactams 22a; Typical Pro-
cedure
To a refluxing solution of iodo b-lactam 22a (0.231 g, 0.42 mmol)
in toluene (40 mL) was added a solution of Bu3SnH (0.183 g, 0.63
mmol) and AIBN (13 mg) in toluene (20 mL) slowly through a sy-
ringe pump in 2 h. The reaction mixture was further refluxed for 4
h. The solvent was evaporated under reduced pressure and the crude
material was purified by flash chromatography (10% acetone–pe-
troleum ether). A pale yellow solid was obtained, which was further
purified by washing with anhyd EtOH to get exo cyclized tetracy-
clic b-lactam 24a (64.4 mg, 36%).
MS: m/z = 422 [M + 1].
Radical Cyclization of 23b
b-Lactam 23b (0.12 g, 0.214 mmol) also gave an inseparable dia-
stereomeric mixture (55:45) of cyclized product 25b (52 mg, 56%).
Compound 24a
White solid; mp 160–161 °C; [a]D25 +25.87 (c = 1.55, CHCl3)
IR (CHCl3): 1763 cm–1.
Compound 25b
1H NMR (CDCl3, 200 MHz): d = 1.37 (s, 3 H, CH3), 1.43 (s, 3 H,
CH3), 2.31–2.43 (m, 1 H, H-13), 2.54–2.87 (m, 4 H, H-6, H-12, H-
14), 3.51 (dd, J = 5.5 Hz, 13.3 Hz, 1 H, H-12), 3.90 (t, J = 3.9 Hz, 1
H, H-4), 4.76–4.84 (m, 2 H, H-5, H-7), 5.31 (d, J = 3.9 Hz, 1 H, H-
3), 5.91 (d, J = 3.9 Hz, 1 H, H-8), 7.01–7.35 (m, 10 H, aromatic).
13C NMR (CDCl3, 125.76 MHz): d = 27.1, 27.3, 35.5, 37.3, 39.1,
47.5, 55.0, 72.5, 81.3, 82.00, 106.5, 115.7, 122.5, 126.7, 128.7,
129.0, 129.6, 138.4, 157.0, 165.7.
White crystalline solid; mp 190–191 ºC.
IR (CHCl3): 1757 cm–1.
1H NMR (CDCl3, 500 MHz): d = 1.26 (s, 3 H, CH3), 1.27 (s, 3 H,
CH3), 1.43 (s, 3 H, CH3), 1.47 (s, 3 H, CH3), 1.87–1.90 (dd, J = 2.8,
11.0 Hz, 1 H, H-13), 1.95–2.03 (m, 3 H, H-13, H-6), 2.26 (dd, J =
10.1, 13.8 Hz, 2 H, H-14), 2.40 (t, J = 6.0 Hz, 1 H, H-14), 2.47 (dd,
J = 10.6, 13.8 Hz, 1 H, H-14), 2.64 (dd, J = 5.0 Hz, 13.7 Hz, 1 H,
H-12), 2.83 (dd, J = 4.2 Hz, 12.4 Hz, 1 H, H-12), 2.89–2.95 (m, 2
H, H-12), 3.32 (t, J = 3.2 Hz, 1 H, H-4), 3.54 (dd, J = 5.0, 13.7 Hz,
1 H, H-12), 4.08 (br s, 2 H, PhCH2O), 4.24 (d, J = 5.5 Hz, 1 H, H-
4), 4.46 (d, J = 3.7 Hz, 1 H, H-5), 4.50 (d, J = 5.0 Hz, 1 H, H-3),
4.52 (d, J = 5.0 Hz, 1 H, H-3), 4.66 (d, J = 3.2 Hz, 2 H, H-5, H-7),
4.68 (d, J = 11.5 Hz, 1 H, PhCH2O), 4.72 (t, J = 3.9 Hz, 1 H, H-7),
4.77 (d, J = 11.5 Hz, 1 H, PhCH2O), 5.86 (d, J = 3.6 Hz, 2 H, H-8),
6.99–7.44 (m, aromatic).
MS: m/z = 422 [M + 1].
Anal. Calcd for C25H27NO5: C, 71.24; H, 6.45; N, 3.32. Found: C,
71.38; H, 6.60; N, 3.18.
Radical Cyclization of 22b
The radical cyclization of b-lactam 22b (0.233 g, 0.42 mmol) was
carried out using the above procedure and the crude product was pu-
rified by chromatography to afford 24b (50 mg, 28%).
13C NMR (125 MHz, CDCl3): d = 25.9, 26.3, 26.5, 27.0, 32.9, 34.9,
36.3, 38.3, 39.9, 40.3, 47.1, 48.3, 53.0, 53.2, 71.4, 73.8, 73.9, 81.0,
81.6, 82.0, 83.6, 105.2, 105.5, 126.5, 126.7, 128.0, 128.4, 128.6,
128.7, 128.8, 128.9, 128.9, 136.8, 137.1, 137.6, 138.7, 165.3, 169.5.
Compound 24b
Pale yellow solid; mp 135–136 °C; [a]D25 +34.14 (c = 1.60, CHCl3).
IR (CHCl3): 1760 cm–1.
MS: m/z = 436 [M + 1].
Synthesis 2004, No. 18, 2965–2974 © Thieme Stuttgart · New York