Z. S. Massen et al. / Carbohydrate Research 346 (2011) 230–237
235
(CDCl3) d 5.05 (s, 1H), 4.81 (d, J = 5.5 Hz, 1H), 4.69 (m, 2H4.24 (q,
J = 7.3 Hz, 2H), 3.37 (s, 3H), 2.30 (m, 1H), 2.05 (m, 2H), 1.70 (m,
1H), 1.50 (s, 9H), 1.46 (s, 3H), 1.32 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H);
13C NMR (CDCl3) d 169.6, 154.6, 113.3, 112.8, 109.4, 84.7, 81.6,
81.1, 61.4, 55.3, 55.1, 28.2, 26.3, 25.8, 24.9, 22.3, 14.2; HRMS (m/
z) calcd for C19H31NO9Na [(M+Na)+] 440.18910, found 440.18924.
reaction was then quenched by the addition of saturated aqueous
NaHCO3, and the mixture was extracted with CH2Cl2. The com-
bined organic extracts were washed with brine, dried over Na2SO4,
filtered, and concentrated in vacuo to afford 0.35 g of 22 (60%) as a
colorless oil. ½a D25
ꢂ45.8 (c 4.47, CHCl3); FTIR (film) 3480, 2982,
ꢃ
2940, 2873, 1738, 1715, 1455, 1372, 1314, 1212, 1161, 1020,
; d 5.04 (d, J = 5.8 Hz, 1H), 4.80
871 cmꢂ1 1H NMR (CDCl3)
3.5.2. (3aR,30S,4S,6R,6aR)-20-tert-Butyl 30-ethyl 6-((tert-
butyldimethylsilyloxy)methyl)-2,2-dimethyldihydro-3aH-
spiro[furo[3,4-d][1,3]dioxole-4,60-morpholine]-20,30-
dicarboxylate (21)
(d, J = 5.8 Hz, 1H), 4.65 (br s, 1H), 4.4 (d, J = 2.7 Hz, 1H), 4.25
(q, J = 7.1 Hz, 2H), 3.86 (d, J = 13.1 Hz, 1H), 3.68 (m, 1H), 2.37
(m, 1H), 2.08 (m, 2H), 1.65 (m, 1H), 1.50 (s, 12H), 1.35 (s, 3H),
1.29 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3) d 169.2, 155.5, 112.2,
87.6, 82.8, 81.8, 64.1, 61.8, 56.5, 28.1, 26.2, 26.1, 24.5, 22.3, 14.1;
HRMS (m/z) calcd for C19H32NO9 [(M+H)+] 418.20771, found
418.20768.
This compound was isolated in 60% yield. ½a D25
ꢂ46.4 (c 3.9,
ꢃ
CHCl3); FTIR (film) 2980, 2956, 2858, 1738, 1713, 1473, 1369,
1252, 1209, 1163, 1101, 838, 778 cmꢂ1 1H NMR (CDCl3) d 4.75
;
(two dd, J = 11.4, 6.1 Hz, 2H), 4.70 (m, 1H), 4.20 (m, 3H), 3.77 (d,
J = 8.9 Hz, 1H), 3.75 (d, J = 3.7 Hz, 1H), 2.32 (br d, J = 11.8 Hz, 1H),
2.10 (m, 1H), 2.02 (m, 1H), 1.68 (ddd, J = 18.0, 13.3, 4.9 Hz, 1H),
1.51 (s, 9H), 1.47 (s, 3H), 1.34 (s, 3H), 1.26 (t, J = 7.1 Hz, 3H), 0.88
(s, 9H), 0.06 (s, 3H), 0.05 (s, 3H); 13C NMR (75 MHz, CDCl3) d
169.4, 154.6, 112.6, 87.3, 82.4, 81.8, 81.4, 63.7, 61.5, 54.9, 28.3,
26.4, 25.9, 25.5, 25.1, 22.4, 18.2, 14.1, ꢂ5.3, ꢂ5.4; HRMS (m/z) calcd
for C25H46NO9Si [(M+H)+] 532.29364, found 532.29378.
3.7. (3aR,30S,4S,6R,6aR)-20-tert-Butyl 30-ethyl 6-(acetoxymethyl)-
2,2-dimethyldihydro-3aH-spiro[furo[3,4-d][1,3]dioxole-4,60-
tetrahydrooxazine]-20,30-dicarboxylate (23)
To a solution of 22 (0.2 g 0.48 mmol) in dry pyridine, were
added 0.07 mL (1.5 equiv) Ac2O at 0 °C, and the reaction mixture
was stirred under argon atmosphere, at room temperature for
8 h. Pyridine was then concentrated in vacuo and the residue
was dissolved in CH2Cl2 and washed with saturated aqueous NaH-
CO3. The organic layer was dried over Na2SO4, concentrated, and on
a silica gel column with hexane/ethyl acetate 1:7 as the eluent to
3.5.3. (3R,6R,8S,9R,10R,11S)-2-tert-Butyl 3-ethyl 9,10,11-
tris(benzyloxy)-8-methoxy-1,7-dioxa-2-azaspiro[5.5]undecane-
2,3-dicarboxylate (31)
This compound was isolated in 50% yield. ½a D25
ꢃ
+48.1 (c 0.52,
give 0.21 g of the acetylated derivative 23 in 95% yield. ½a D25
ꢃ
CHCl3). FTIR (film) 2925, 2851, 1738, 1712, 1455, 1367, 1313,
ꢂ39.6 (c 6.6, CHCl3); FTIR (film) 2982, 2940, 1747, 1712, 146,
1254, 1158, 1097 cmꢂ1
;
1H NMR (CDCl3) d 7.29 (m, 15H), 4.84 (d,
1372, 1312, 1211, 1163, 1097, 1038, 1020, 973 cmꢂ1 1H NMR
;
J = 11.6 Hz, 1H), 4.83 (d, J = 8.9 Hz, 1H), 4.77 (d, J = 11.6 Hz, 1H),
4.75 (s, 1H), 4.70 (d, J = 8.9 Hz, 1H), 4.69 (d, J = 12.2 Hz, 1H), 4.59
(d, J = 11.3 Hz, 1H), 4.38 (dd, J = 6.1, 4.6 Hz, 1H), 4.25 (m, 2H),
3.98 (m, 2H), 3.80 (d, J = 5.5 Hz, 1H), 3.47 (s, 3H), 2.28 (m, 1H),
2.02 (m, 2H), 1.84 (m, 1H), 1.42 (s, 9H), 1.27 (t, J = 7.0 Hz, 3H);
13C NMR (CDCl3) d 179.1, 155.2, 138.5, 138.2, 138.1, 128.4, 128.3,
128.1, 127.9, 127.7, 127.6, 105.2, 98.1, 82.1, 81.4, 78.3, 78.2, 74.6,
73.8, 73.5, 61.3, 58.0, 56.5, 28.1, 27.4, 21.7, 14.1; HRMS (m/z) calcd
for C38H48NO10 [(M+H)+] 678.32782, found 678.32777.
(CDCl3) d 4.83 (d, J = 6.1 Hz, 1H), 4.75 (d, J = 6.1 Hz, 1H), 4.70 (d,
J = 4.0 Hz, 1H), 4.37 (dd, J = 8.6, 6.1 Hz, 1H), 4.32 (m, 2H), 4.23 (q,
J = 7.2 Hz, 2H), 2.36 (m, 1H), 2.13 (m, 1H), 2.08 (s, 3H), 1.99 (m,
1H), 1.72 (m, 1H), 1.51 (s, 9H), 1.49 (s, 3H), 1.35 (s, 3H), 1.28 (t,
J = 7.2 Hz, 2H); 13C NMR (CDCl3) d 170.3, 169.2, 154.6, 113.0,
112.7, 84.1, 82.4, 82.1, 81.3, 64.5, 61.5, 54.9, 28.2, 28.0, 25.0,
22.3, 20.7, 14.1; HRMS (m/z) calcd for C21H34NO10 [(M+H)+]
460.21827, found 460.21812.
3.8. (3S,6R,8R,9R,10S,11R)-2-tert-Butyl 3-ethyl 9,10,11-
triacetoxy-8-(acetoxymethyl)-1,7-dioxa-2-
azaspiro[5.5]undecane-2,3-dicarboxylate (36)
3.5.4. (3S,6R,8R,9R,10S,11R)-2-tert-Butyl 3-ethyl 9,10,11-
tris(benzyloxy)-8-(benzyloxymethyl)-1,7-dioxa-2-
azaspiro[5.5]undecane-2,3-dicarboxylate (35)
This compound was isolated in 50% yield. ½a D25
ꢃ
+26.1 (c 0.98,
To a solution of 35 (30 mg, 0.04 mmol) in MeOH, a catalytic
amount of Pd/C was added, and the mixture was stirred overnight
under hydrogen atmosphere at the boiling point of the solvent.
After total removal of all protecting benzyl groups, the catalyst
was filtered through Celite and the filtrate was concentrated. With-
out further purification the crude residue was dissolved in 2 mL of
pyridine. To this solution, 0.02 mL Ac2O (2.5 equiv/JY group) were
added at 0 °C. The reaction mixture was stirred at room tempera-
ture and under inert atmosphere for 8 h, then pyridine was re-
moved under reduced pressure and the residue was diluted with
CH2Cl2 and washed with brine. The aqueous phase was extracted
with ethyl acetate and the combined organic layers were dried
over Na2SO4 and concentrated. The residue was flash chromato-
graphed to give 16 mg of the total acetylated derivative 36, in
70% yield for the two steps. FTIR (film) 2927, 2854, 1755, 1369,
CHCl3); FTIR (film) 3064, 3031, 2977, 2931, 2852, 1747, 1732,
1714, 1497, 1455, 1367, 1327, 1093 cmꢂ1 1H NMR (CDCl3) d 7.20
;
(m, 20H), 4.96 (d, J = 11.3 Hz, 1H), 4.88 (s, 2H), 4.86 (d,
J = 13.5 Hz, 1H), 4.39 (m, 1H), 4.59 (m, 4H), 4.26 (dd, J = 7.3,
3.6 Hz, 1H), 3.75 (d, J = 9.15 Hz, 1H), 3.72 (d, J = 10.2 Hz, 1H), 3.47
(d, J = 9.5 Hz, 1H), 1.65 (m, 3H), 1.49 (m, 1H), 1.43 (s, 9H), 1.23 (t,
J = 7.1 Hz, 3H); 1H NMR (CDCl3/C6D6, 3:2) d 7.20 (m, 20H), 4.85
(d, J = 11.3 Hz, 1H), 4.82 (s, 2H), 4.80 (d, J = 10.8 Hz, 1H), 4.54 (m,
3H), 4.40 (m, 1H), 4.20 (dd, J = 7.3, 4.2 Hz, 1H), 4.14 (t, J = 9.7 Hz,
1H), 4.04 (m, 2H), 3.69 (m, 3H), 3.37 (d, J = 9.7 Hz, 1H), 2.05 (m,
1H), 1.75 (m, 2H), 1.60 (m, 1H), 1.36 (s, 9H), 1.08 (t, J = 7.1 Hz,
3H); 13C NMR (CDCl3) d 170.4, 138.8, 138.8, 138.6, 138.4, 137.6,
128.8, 128.5, 128.4, 128.3, 128.2, 127.9, 127.7, 127.3, 127.2,
103.4, 83.3, 83.0, 82.1, 78.4, 76.0, 75.8, 74.4, 73.3, 72.6, 68.5,
61.0, 58.5, 29.7, 28.2, 22.8, 14.1; HRMS (m/z) calcd for
1219, 1035 cmꢂ1 1H NMR (CDCl3) d 5.5 (t, J = 9.6 Hz, 1H), 5.17
;
C
45H54NO10 [(M+H)+] 768.37477, found 768.37483.
(d, J = 9.8 Hz, 1H), 5.13 (dd, J = 10.1, 3.7 Hz, 1H), 4.59 (m, 1H),
4.25 (m, 2H), 4.22 (q, J = 7.0 Hz, 2H), 4.10 (d, J = 12.5 Hz, 1H), 2.10
(s, 3H), 2.09 (s, 3H), 2.02 (s, 3H), 2.00 (m, 3H), 1.99 (s, 3H), 1.88
(m, 1H), 1.51 (s, 9H), 1.28 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3) d
170.9, 170.0 (two peaks), 169.8, 169.7, 154.7, 101.8, 82.8, 73.1,
71.0, 69.3, 68.3, 61.7, 61.3, 58.3, 29.8, 28.1, 27.7, 22.1, 20.8, 20.7,
14.1; HRMS (m/z) calcd for C25H38NO14 [(M+H)+] 576.22923, found
576.22929.
3.6. (3aR,30S,4S,6R,6aR)-20-tert-Butyl 30-ethyl 6-
(hydroxymethyl)-2,2-dimethyldihydro-3aH-spiro[furo[3,4-d
][1,3]dioxole-4,60-tetrahydrooxazine]-20,30-dicarboxylate (22)
Compound 21 (0.446 g, 0.82 mmol) was dissolved in THF/AcOH/
H2O (4:13:7 v/v/v) and the mixture was stirred for 4 h at rt. The