E. Avallone et al. / Tetrahedron 61 (2005) 10689–10698
10697
43.0, 47.3, 53.0, 55.0, 56.6, 62.0, 68.9, 70.2, 70.5, 70.8 (!
4), 71.2, 72.9, 171.0. HRES-MS, m/z: 553.4110 (calcd
4.7. Procedures for the synthesis of compounds
described in Scheme 6
553.4104 for C32H57O7) [MHC].
4.7.1. Compound 29. To a solution of 12 (0.600 g,
1.80 mmol) in dichloromethane (10 ml) at 0 8C, pyridine
(5 ml) and acetic anhydride (0.5 ml) were sequentially
added. The reaction mixture was allowed to warm to rt,
stirred overnight and quenched with a solution of HCl (2 M,
3 ml). The aqueous layer was extracted three times with
dichloromethane, the organic layer was dried over Na2SO4,
filtered, evaporated in vacuo and purified by flash
chromatography (silica gel, 10–15% ethyl acetate in
petroleum ether) to furnish 29 (0.338 g, 50%) as a white
amorphous solid.
4.6. Procedures for the synthesis of compounds
described in Scheme 5
4.6.1. Compound 28. To a solution of 27 (0.088 g,
0.146 mmol) in CH2Cl2 (0.5 ml) at rt, DMAP (0.055 g,
0.45 mmol), a solution of 23 (0.080 g, 0.163 mmol) in
CH2Cl2 (1 ml) and EDC (0.140 g, 0.73 mmol) were
sequentially added. The reaction mixture was stirred for
16 h, quenched with water (2 ml) and extracted with ethyl
acetate (4 ml). The organic layer was washed with a
saturated solution of NaHCO3, with water, dried over
Na2SO4, filtered and concentrated in vacuo. The crude was
purified by flash chromatography (silica gel, 0–1%
methanol in CHCl3) to afford 28 (0.049 g, 31%) as a
white amorphous solid.
Compound 29. RfZ0.45 (30% ethyl acetate in petroleum
ether). [a]D C12.3 (c 2.5 in CHCl3). H NMR (400 MHz,
1
CDCl3) d: 0.65 (3H, s, CH3-18), 0.78 (3H, s, CH3-19), 0.97
(3H, d, JZ6.6 Hz, CH3-21), 2.03 (3H, s, CH3CO–), 3.55
(1H, m, H-3), 3.75 (1H, dd, JZ10.6, 7.6 Hz, H-22), 4.05
(1H, dd, JZ10.6, 3.4 Hz, H0-22). 13C NMR (400 MHz,
CDCl3) d: 12.0, 12.2, 17.0, 20.9, 21.2, 24.2, 27.6, 28.6, 31.4,
32.0, 35.4, 35.5, 35.7, 37.0, 38.1, 39.8, 42.7, 44.8, 52.8,
54.3, 56.1, 69.5, 71.2, 171.3. HRES-MS, m/z: 377.3019
(calcd 377.3056 for C24H41O3) [MHC].
Compound 28. RfZ0.3 (5% methanol in CHCl3). [a]D
C14.0 (c 1.7, CHCl3). 1H NMR (400 MHz, CDCl3) d: 0.74
(3H, s, CH3-18), 0.87 (3H, s, CH3-19), 1.02 (3H, d, JZ
6.9 Hz, CH3-21), 1.05 (9H, s, (CH3)3Si–), 2.48 (1H, m,
H-20), 3.08 (1H, m, H-6 or H-7), 3.27 (1H, m, H-7 or H-6),
3.59–3.70 (15H, m, –(OCH2CH2O)3CH2– and H-3, over-
lapped), 3.81, (2H, m, –CH2OTPS), 4.04 (1H, m, H-22),
4.13 (2H, br s, OCOCH2O), 4.25 (1H, m, H0-22), 5.41 (1H,
s, H-16), 7.34–7.40 (6H, m, Ar-H), 7.66–7.68 (4H, m,
Ar-H). 13C NMR (400 MHz, CDCl3) d: 13.6, 16.1, 18.7,
19.2, 20.9, 26.8 (!3), 26.9 (!3), 31.3 (!2),, 32.2, 33.9,
34.5, 35.9, 37.1, 39.8, 47.6, 48.0, 52.2, 55.8, 63.4, 68.6,
68.7, 70.6 (!4), 70.7 (!2), 70.9, 72.4, 72.5, 74.8, 80.3,
123.5, 127.4 (!4), 127.6 (!4), 129.5 (!2), 129.6 (!2),
133.7 (!2), 134.6, 134.8, 135.6 (!4), 135.8 (!4), 155.4,
170.4; HRES-MS, m/z: 1077.6326 (calcd 1077.6307 for
C64H93O10Si2) [MHC].
4.7.2. Compound 30. To a solution of 29 (0.116 g,
0.308 mmol) in CH2Cl2 (1 ml) at rt, DMAP (0.123 g,
1.00 mmol), a solution of 23 (0.200 g, 0.407 mmol) in
CH2Cl2 (1 ml) and EDC (0.321 g, 1.67 mmol) were
sequentially added. The reaction mixture was stirred for
24 h, quenched with water (2 ml) and extracted with ethyl
acetate (4 ml). The organic layer was washed with a
saturated solution of NaHCO3, with water, dried over
Na2SO4, filtered and concentrated in vacuo. The crude was
purified by flash chromatography (silica gel, 10–40% ethyl
acetate in petroleum ether) to afford 30 (0.214 g, 82%) as a
white amorphous solid.
Compound 30. RfZ0.3 (30% ethyl acetate in petroleum
ether). [a]D C4.4 (cZ1.1 in CHCl3). H NMR (400 MHz,
1
4.6.2. Compound 4. To a solution of 28 (0.060 g,
0.056 mmol) in pyridine (0.3 ml) at 0 8C, a solution of
70% hydrofluoric acid in pyridine (200 ml, 7.00 mmol) was
added. The reaction mixture was stirred for 1.5 h and
concentrated under a stream of N2. The residue was purified
by flash chromatography (silica gel, 30–70% ethyl acetate in
petroleum ether) to afford 4 (0.017 g, 51%) as a white
amorphous solid.
CDCl3) d: 0.67 (3H, s, CH3-18), 0.81 (3H, CH3-19), 1.00
(3H, d, JZ6.7 Hz, CH3-21), 1.04 (9H, s, (CH3)3Si–), 2.04
(3H, s, CH3CO), 3.63–3.74 (14H, m, (OCH2CH2O)3CH2–),
3.76, (1H, m, H-22), 3.80 (2H, m, –CH2OTPS), 4.07 (1H, m,
H0-22), 4.09 (2H, br s, COCH2O), 4.76 (1H, m, H-3), 7.34–
7.41 (6H, m, Ar-H), 7.66–7.68 (4H, m, Ar-H). 13C NMR
(400 MHz, CDCl3) d: 12.0, 12.2, 17.0, 19.1, 20.9, 21.1,
24.2, 26.8 (!3), 27.4, 27.6, 28.5, 31.8, 33.9, 35.4 (!2),
35.7, 36.6, 39.7, 42.7, 44.5, 52.8, 54.1, 56.0, 63.4, 68.8,
69.4, 70.5(!4), 70.7, 70.8, 72.4, 74.2, 127.5 (!4), 129.5
(!2), 133.7 (!2), 135.5(!4), 169.9, 171.2. HRES-MS,
m/z: 849.5341 (calcd 849.5337 for C50H77O9Si) [MHC].
Compound 4. RfZ0.1 (8% methanol in CHCl3). [a]D C41.3
(c 0.8 in CHCl3). 1H NMR (400 MHz, CDCl3) d: 0.75 (3H,
s, CH3-18), 0.87 (3H, s, CH3-19), 1.04 (3H, d, JZ6.8 Hz,
CH3-21), 2.46 (1H, m, H-20), 3.09 (1H, m, H-6 or H-7), 3.24
(1H, m, H-7 or H-6), 3.54 (1H, m, H-3), 3.58 (2H, m,
CH2OH), 3.67–3.71 (14H, m, –(OCH2CH2O)3CH2–), 3.99
(1H, dd, JZ10.5, 7.9 Hz, H-22), 4.12 (2H, s, COCH2O),
4.21 (1H, dd, JZ10.5, 6.4 Hz, H0-22), 5.42 (1H, s, H-16).
13C NMR (400 MHz, CDCl3) d: 13.6, 16.1, 18.7, 21.0, 30.7,
31.4, 32.3, 33.9, 34.6, 35.9, 37.1, 39.8, 47.7, 48.1, 52.3,
55.9, 61.6, 68.6, 68.7, 70.2, 70.4 (!4), 70.8, 72.1, 72.6,
74.6, 80.1, 123.7, 155.3, 170.5. HRES-MS, m/z: 601.3948
(calcd 601.3952 for C32H57O10) [MHC].
4.7.3. Compound 5. To a solution of 30 (0.214 g,
0.252 mmol) in pyridine (0.4 ml) at 0 8C a solution of
70% hydrofluoric acid in pyridine (200 ml, 7.00 mmol) was
added. The reaction mixture was stirred for 1.5 h and
concentrated under a stream of N2. The residue was purified
by flash chromatography (silica gel, 30–70% ethyl acetate in
petroleum ether) to afford 5 (0.126 g, 82%) as a white
amorphous solid.