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Med Chem Res (2008) 17:326–334
extracted with ether (4 9 25 mL), solvent was distilled off, and the crude product
was purified by column chromatography over silica gel to furnish compound 5 (660
mg, 68% yield). IR (KBr, cm-1) 1727; 1H NMR (200 MHz, CDCl3) d 0.78 (s, 3H),
0.88 (s, 3H), 1.01 (d, 3H, J = 6.8 Hz), 1.26–1.85 (m, 21H), 2.04 (s, 3H), 2.12 (s,
3H), 2.18–2.31 (m, 1H), 4.07–4.09 (m, 1H), 5.06 (bs, 1H), 9.55 (d, 1H, J = 2.9 Hz),
FAB-MS (m/z): 433 [M + H]+.
Acetic acid 3-acetoxy-17-(3-iodo-1-methyl-propyl)-10,13-dimethyl-
hexadecahydro-cyclopenta[a]phenanthren-12-yl ester (6)
A solution of diacetyl deoxycholic acid 2 (0.5 g, 1.1 mmol), Pb(OAc)4 (0.6 g, 1.2
eq.) and iodine (0.66 g, 2.5 eq.) in CCl4 (15 mL) was irradiated with a 500-W
tungsten-halogen lamp for 30 min. The reaction mixture was quenched by adding
saturated Na2S2O3 solution and extracted with dichloromethane (3 9 25 mL), dried
over Na2SO4, concentrated, and the crude product was purified by column
chromatography over silica gel to furnish compound 6 (0.2 g, 29% yield). IR (KBr,
cm-1) 1727; 1H NMR (200 MHz, CDCl3) d 0.75 (s, 3H), 0.81 (d, 3H, J = 5.8 Hz),
0.91 (s, 3H), 1.01–1.95 (m, 24H), 2.03 (s, 3H), 2.09 (s, 3H), 3.01–3.13 (m, 1H),
3.24–3.33 (m, 1H), 4.65–4.76 (m, 1H), 5.08 (bs, 1H); FAB-MS (m/z): 559 [M + H]+,
497 [M + H - AcOH]+, 439 [M + H – 2 AcOH]+.
General procedure for the preparation of compounds 8a–e (preparation of 8d as
representative)
Aldehyde 5 (300 mg, 0.7 mmol), 4-aminoquinoline 7d (330 mg, 1.4 mmol), and glacial
acetic acid (0.1 mL) in CH2Cl2 (50 mL) were stirred at room temperature for 30 min.
NaBH(OAc)3 (330 mg, 1.03 mmol) was added portionwise for over 3 h and the
reaction mixture was stirred for another 6 h. The reaction mixture was quenched with
water (50 mL) and extracted with CH2Cl2 (3 9 30 mL), solvent was removed under
reduced pressure, and the crude product was purified by column chromatography over
silica gel to furnish compound 8d (230 mg, 51% yield). mp 113–115°C. IR (KBr, cm-
1) 3399; 1H NMR (200 MHz, CDCl3) d 0.72 (s, 3H), 0.91 (s, 3H), 0.99 (d, 3H, J = 6.0
Hz), 1.08–1.84 (m, 25H), 2.03 (s, 3H), 2.09 (s, 3H), 2.48 (t, 1H, J = 8.0 Hz), 2.81 (t,
1H, J = 8.0 Hz), 3.01 (bs, 2H), 3.46 (bs, 2H), 4.70 (m, 1H), 5.07 (bs, 1H), 5.96 (bs, 1H,
NH), 6.27 (d, 1H, J = 5.8 Hz), 7.34 (dd, 1H, J = 8.8 and 1.4 Hz), 7.89 (d, 1H, J = 1.4
Hz), 8.11 (d, 1H, J = 8.8 Hz), 8.31 (d, 1H, J = 5.8 Hz); FAB-MS (m/z): 652 [M + H]+,
592 [M + H - AcOH]+, 532 [M + H – 2 AcOH]+.
Compounds 8a-c and 8e were prepared by the above procedure.
Acetic acid 12-acetoxy-10,13-dimethyl-17-(1-methyl-2-phenylamino-ethyl)-
hexadecahydro-cyclopenta[a]phenanthren-3-yl ester (8a)
1
IR (KBr, cm-1) 3433; H NMR (300 MHz, CDCl3) d: 0.73 (s, 3H), 0.89 (d, 3H,
J = 5.4 Hz), 0.90 (s, 3H), 1.01–1.88 (m, 23H), 2.03 (s, 3H), 2.09 (s, 3H), 2.29 (dd,