S. Arseniyadis et al. / Tetrahedron: Asymmetry 9 (1998) 4055–4071
4069
Elution with heptane:ethyl acetate, 2:1, afforded first the C-9 oxidized derivatives 15 and 16 which
served as B-like substrates (Scheme 5) in, otherwise unsuccessful, retro-aldol type II fragmentation
experiments.
1
5: mp: 188–190°C (heptane:ether). IR (film): 2987, 2967, 2939, 2875, 1737, 1460, 1381, 1372, 1226,
−1 1
1
199, 1112, 1001, 871 cm . H NMR (400 MHz): 0.92 (3H, s), 1.19 (3H, s), 1.41 (3H, s), 1.42 (3H, s),
1.45 (3H, s), 1.51 (3H, s), 1.72 (1H, t, J=13.8), 1.86 (1H, dd, J=9.5, 13.8), 1.92–2.08 (1H, m), 2.11–2.14
(
2H, m), 2.22 (1H, dd, J=1.9, 13.6), 2.76 (1H, ddd, J=1.9, 9.5, 13.8), 3.31 (1H, bs, OH), 3.33 (1H, dd,
J=4.5, 8.3), 3.77 (1H, t, J=11.1), 3.96–4.03 (4H, m), 4.16–4.24 (2H, m), 5.66 (1H, d, J=10.0), 5.84
1H, dd, J=2.4, 10.0). 13C NMR (62.9 MHz): 18.9, 24.3, 25.7, 27.2, 28.3, 29.6, 37.1, 39.3, 39.5, 41.5,
2.4, 53.8, 57.5, 59.9, 64.6, 64.7, 65.3, 69.6, 72.7, 85.3, 98.5, 109.2, 128.1, 131.6, 218.1. Anal. calcd for
C H O : C 66.94, H 8.09, found: C 66.89, H 8.12.
(
5
25
36
7
1
6: mp: 224–226°C (heptane:ether). [α] −14.3 (c 1.29). IR (film): 3469, 2987, 2968, 2939, 2876,
D
1
8
1
2
737, 1465, 1382, 1374, 1301, 1268, 1230, 1219, 1200, 1168, 1115, 1084, 1052, 1000, 948, 918, 896,
−1 1
57 cm . H NMR (300 MHz): 0.93 (3H, s), 1.20 (3H, s), 1.44 (6H, s), 1.45 (3H, s), 1.51 (3H, s),
.76 (1H, dd, J=9.1, 13.9), 1.94 (1H, dd, J=1.8, 13.4), 2.03 (1H, dd, J=13.5, 13.9), 2.04–2.09 (2H, m),
.39 (1H, dddd, J=4.1, 9.5, 11.1, 13.5), 2.71 (1H, ddd, J=1.8, 9.1, 13.5), 3.19 (1H, OH, s), 3.29 (1H,
dd, J=3.7, 9.1), 3.33 (1H, d, J=4.5), 3.37 (1H, d, J=4.5), 3.64 (1H, t, J=11.1), 3.96–4.04 (4H, m), 4.03
13
(
1H, d, J=9.5), 4.11 (1H, dd, J=4.1, 11.1). C NMR (62.9 MHz): 18.8, 24.3, 25.2, 25.6, 27.3, 29.5, 33.7,
3
6.3, 37.1, 39.3, 50.7, 52.7, 54.3, 57.2, 57.3, 60.1, 64.6, 64.8, 64.9, 70.7, 72.5, 86.1, 98.7, 109.2, 218.4.
+
CIMS: 465 ([M+H] , 100), 447 (24), 407 (24), 403 (53), 389 (30), 345 (40), 87 (99). HRCIMS: calcd for
C H O m/z 465.2488, found: 465.2479. Anal. calcd for C H O : C 64.64, H 7.81, found: C 64.39,
25
37
8
25 36
8
H 7.97.
1
7: mp: 210–212°C (heptane:EtOAc). [α] −45 (c 1.31). IR (film): 3451, 2991, 2981, 2875, 1460,
D
−1 1
1
384, 1374, 1268, 1255, 1230, 1217, 1196, 1170, 1101, 1055, 1039, 996, 755 cm . H NMR (300
MHz): 0.91 (3H, s, Me-16), 1.17 (3H, s, Me-17), 1.39 (3H, s, Me-19), 1.42 (3H, s, Me-18), 1.43 (3H,
s, Me-eq acetonide), 1.45–1.52 (2H, m, H-11, H-3), 1.48 (3H, s, Me-ax acetonide), 1.94 (1H, t, J=13.4,
H-11), 1.98–2.05 (2H, m, H-13), 2.35 (1H, m, H-4), 2.61 (1H, ddd, J=7.4, 8.0, 13.4, H-10), 2.89 (1H,
s, OH), 3.20 (1H, d, J=4.7, H-7), 3.22 (1H, dd, J=4.5, 8.1, H-14), 3.33 (1H, d, J=4.7, H-6), 3.53 (1H,
t, J=11.1, H-20ax), 3.92–4.03 (4H, m, -OCH CH O-), 3.98 (1H, d, J=9.8, H-5), 3.99 (1H, dd, J=4.7,
2
2
11.1, H-20eq), 4.27 (1H, d, J=7.4, H-9). Diagnostic NOEs: {Me-16}: Me-17 (NOE gem), H-14, H-11β,
H-10; {Me-19}: H-3, H-9, H-7, H-5; {Me-βax of acetonide}: H-20β-ax, H-5; {H-5}: H-3, H-6, Me-ax
acetonide, H-20ax; {H-6}: H-7, H-5; {H-7}: Me-19, H-6; {H-14}: Me-16, Me-17, H-13. 13C NMR (62.9
MHz): 18.7 (Me-ax acetonide), 24.1 (Me-18), 25.4 (Me-17), 27.5 (Me-16), 29.4 (Me-eq acetonide), 29.6
(Me-19), 34.2 (C-4), 34.7 (C-11), 37.0 (C-13), 37.9 (Cq), 46.3 (Cq), 53.6 (C-6), 54.3 (C-3), 56.8 (C-14),
5
8
3
7.0 (C-10), 57.6 (C-7), 64.4, 64.6 (-OCH CH O-), 65.0 (C-20), 70.6 (C-5), 72.6 (Cq-O), 82.2 (C-9),
2 2
+
7.3 (Cq-O), 98.4 (C-12), 109.2 (Cq-acetonide). CIMS: 467 ([M+H] , 96), 449 (54), 409 (17), 405 (79),
91 (57), 347 (55), 329 (23), 87(100). HRCIMS: calcd for C H O m/z 467.2645, found: 467.2640.
25
37
8
Anal. calcd for C H O : C 64.36, H 8.21, found: C 64.31, H 8.29.
25
38
8
5.13. Setting the stage for the B-ring formation: mesylation protocol
To a stirred solution of 17 (550 mg, 1.18 mmol) in pyridine (10 ml), in the presence of DMAP as
catalyst (few crystals), methanesulfonyl chloride (MsCl, 0.8 ml, 8.2 mmol) was added at 0°C and stirring
continued for 1 h at this temperature (TLC monitoring, CH Cl :MeOH, 96:4 as eluent). The reaction
2
2
was quenched with a saturated aqueous solution of sodium bicarbonate, and extracted with methylene
chloride. The combined extracts were washed with 1 N hydrochloric acid, water, sodium bicarbonate and