Efficient Synthesis of Deoxysugar Part of Versipelostatin
181.3, 171.8, 171.1, 170.7, 170.4, 170.1, 167.6, 147.2, 145.4, 140.4, 135.7,
135.5, 135.1, 129.3, 126.6, 124.1, 120.8, 116.2, 99.6, 99.3, 90.9, 88.0, 84.8,
80.0, 76.4, 75.3, 73.0, 72.6, 70.5, 69.0, 66.7, 66.0, 61.2, 57.5, 55.9, 51.6, 42.0,
39.6, 39.1, 36.9, 36.7, 36.2, 35.0, 34.7, 34.2, 33.9, 33.3, 32.9, 30.9, 30.6, 29.8,
29.7, 29.1, 26.8, 23.4, 22.8, 22.0, 21.6, 21.3, 21.2, 21.0, 20.0, 19.3, 19.0, 18.8,
18.3, 17.6, 16.4, 13.9, 11.5 ppm; IR (neat): n˜ =2933, 1789, 1740, 1681,
1591, 1524, 1457, 1368, 1347, 1243, 1100, 1065 cmꢀ1; HRMS (ESI-TOF)
calcd for C76H109NO23S [M+Na]+ m/z=1458.7009, found: 1458.6974.
3H, J=7.7 Hz), 1.07 (t, 3H, J=7.7 Hz), 1.00 (t, 3H, J=7.7 Hz), 0.98 (d,
3H, J=6.8 Hz), 0.91 (d, 3H, J=6.8 Hz), 0.87 (d, 3H, J=6.8 Hz),
0.86 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): d=206.4, 198.3, 181.2,
171.9, 170.6, 170.4, 170.2, 167.6, 140.4, 135.6, 135.5, 135.2, 126.6, 120.7,
116.1, 99.9, 99.6, 98.7, 90.8, 87.9, 81.8, 80.0, 78.5, 73.0, 72.5, 70.8, 69.2,
68.0, 67.9, 67.8, 66.0, 57.5, 57.3, 42.0, 39.6, 39.1, 37.9, 36.9, 36.1, 36.0, 35.3,
34.6, 34.1, 33.7, 33.1, 32.9, 30.9, 30.6, 29.8, 29.7, 28.9, 27.9, 26.7, 23.4, 22.8,
22.7, 22.0, 21.6, 21.3, 21.2, 21.0, 20.9, 20.0, 19.3, 18.9, 18.6, 18.3, 17.9, 17.8,
16.4, 13.9, 11.5 ppm; IR (neat): n˜ =2970, 2936, 1788, 1743, 1680, 1588,
1455, 1371, 1241, 1154, 1092, 1065, 1011 cmꢀ1; HRMS (ESI-TOF) calcd
for C81H120O25 [M+Na]+ m/z=1515.8016, found: 1515.8007.
24: DBU (20.8 mL, 139 mmol) was added to a stirred solution of 23
(20.0 mg, 13.9 mmol) in CH3CN (500 mL) at 08C. After being stirred at
RT for 3 h, the reaction mixture was poured into saturated aq. NH4Cl.
The aqueous layer was extracted with two portions of ethyl acetate. The
combined extract was washed with 1m HCl, saturated aq. NaHCO3, and
brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue
was chromatographed on silica gel with hexane/ethyl acetate 40:60 to
give 24 (12.8 mg, 10.5 mmol, 75%). ½aꢁ2D1 =ꢀ15.88 (c=0.625, CHCl3);
1H NMR (400 MHz, CDCl3): d=5.42 (brs, 1H), 5.40 (s, 1H), 5.28 (m,
1H), 5.25 (m, 1H), 5.15 (d, 1H, J15,16 =9.7 Hz), 4.96 (brd, 1H, J=2.4 Hz),
4.77 (m, 1H), 4.68 (d, 1H, J1,2ax =9.2 Hz), 4.11 (dd, 1H, J16,37a =2.4 Hz,
26: NaOMe (20.0 mg) was added to a stirred solution of 25 (5.50 mg,
3.68 mmol) in methanol (500 mL) at RT. After being stirred under reflux
for 24 h, the reaction mixture was neutralized with Dowex 50WX4 and
filtered. The filtrate was poured into saturated aq. NH4Cl. The aqueous
layer was extracted with two portions of ethyl acetate. The combined ex-
tract was washed with brine, dried over MgSO4, filtered, and concentrat-
ed in vacuo. The residue was chromatographed on silica gel with CHCl3/
methanol 94:6 to give 26 (3.00 mg, 2.72 mmol, 75%). ½aꢁ2D4 =ꢀ38.98 (c=
0.305, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.82 (brs, 1H), 5.27 (s,
1H), 5.08 (d, 1H, J=10.1 Hz), 5.06 (dd, 1H, J=1.9 Hz, J=9.2 Hz), 4.96
(d, 1H, J=3.4 Hz), 4.81 (dd, 1H, J=1.4 Hz, J=9.2 Hz), 4.11 (m, 1H),
4.08 (m, 1H), 3.92 (brs, 1H), 3.76–3.88 (m, 2H), 3.69 (dq, 1H, J=6.3 Hz,
J=9.2 Hz), 3.55–3.66 (m, 2H), 3.49 (ddd, 1H, J=4.8 Hz, J=11.6 Hz, J=
9.2 Hz), 3.42 (m, 1H), 3.40 (s, 3H), 3.31 (dd, 1H, J=9.2 Hz, J=9.2 Hz),
3.28 (dd, 1H, J=2.9 Hz, J=9.2 Hz), 3.22–3.27 (m, 2H), 2.87 (dd, 1H, J=
10.1 Hz, J=10.1 Hz), 2.84 (s, 1H), 2.54 (q, 1H, J=7.2 Hz), 2.39 (m, 1H),
2.25–2.35 (m, 2H), 2.23 (dd, 1H, J=4.8 Hz, J=13.0 Hz), 2.00–2.17 (m,
7H), 1.95 (m, 1H), 1.86 (dd, 1H, J=8.2 Hz, J=14.0 Hz), 1.79 (m, 1H),
1.53–1.72 (m, 15H), 1.23–1.31 (m, 8H), 1.21 (d, 3H, J=6.3 Hz), 1.11 (m,
1H), 1.05 (d, 3H, J=7.2 Hz), 1.02 (s, 3H), 0.88–0.97 (m, 12H), 0.84 (d,
3H, J=7.2 Hz), 0.66 ppm (m, 1H,); 13C NMR (100 MHz, CDCl3): d=
205.4, 203.0, 166.5, 140.1, 135.3, 135.2, 133.1, 127.5, 121.4, 103.1, 100.6,
99.2, 98.5, 91.4, 87.3, 81.3, 80.7, 78.3, 73.2, 70.7, 70.5, 69.3, 68.4, 68.3, 67.8,
65.0, 61.1, 57.5, 57.4, 48.8, 43.6, 42.0, 41.8, 38.2, 38.0, 37.4, 36.7, 35.7, 35.2,
35.1, 34.9, 33.2, 32.3, 32.0, 31.1, 29.8, 29.0, 23.7, 23.2, 23.1, 22.0, 21.5, 20.5,
20.4, 19.3, 18.1, 17.8, 17.3, 14.8, 12.7 ppm; IR (solid): n˜ =3439, 2961, 2926,
1742, 1624, 1462, 1380, 1059, 1015, 989 cmꢀ1; HRMS (ESI-TOF) calcd for
C61H96O17 [M+Na]+ m/z=1123.6545, found: 1123.6553.
J
gem =11.1 Hz), 3.81 (dq, 1H, J4,5 =9.2 Hz, J5,6 =6.3 Hz), 3.67–3.74 (m,
2H), 3.63 (dq, 1H, J4,5 =9.2 Hz, J5,6 =6.3 Hz), 3.39 (s, 3H, Me), 3.39 (m,
1H), 3.29 (dd, 1H, J3,4 =2.4 Hz, J4,5 =9.2 Hz), 3.20 (brd, 1H, J=6.8 Hz),
3.12 (dd, 1H, J3,4 =J4,5 =9.2 Hz), 2.59 (m, 1H), 2.54 (m, 1H), 2.47 (m,
1H), 2.28–2.42 (m, 5H), 2.25 (dd, 1H, J2eq,2ax =13.0 Hz, J2eq,3 =4.8 Hz),
2.17 (m, 1H), 2.11 (s, 3H, Ac), 2.11 (s, 3H, Ac), 2.03 (s, 3H, Ac), 1.97 (s,
3H, Ac), 1.97 (q, 1H, J35,36 =7.2 Hz), 1.91 (m, 1H), 1.86 (q, 1H, J35,36
=
7.2 Hz), 1.82 (q, 1H, J31,32 =7.2 Hz), 1.74–1.81 (m, 3H), 1.72 (m, 1H),
1.69 (s, 3H), 1.59 (s, 3H), 1.22–1.59 (m, 24H), 1.10 (s, 3H), 1.09 (d, 3H,
J
18,38 =6.8 Hz), 1.07 (t, 3H, J31,32 =7.2 Hz), 1.01 (t, 3H, J35,36 =7.2 Hz), 0.98
(d, 3H, J27,42 =6.8 Hz), 0.91 (d, 3H, J6,33 =6.3 Hz), 0.88 (d, 3H, J20,39
=
6.8 Hz), 0.85 ppm (m, H-17b); 13C NMR (67.8 MHz, CDCl3): d=198.2,
181.2, 171.8, 171.1, 170.6, 170.4, 170.3, 167.6, 140.3, 135.6, 135.5, 135.1,
126.6, 120.7, 116.1, 100.1, 99.6, 90.7, 87.9, 79.7, 78.0, 76.0, 73.0, 72.5, 70.8,
69.2, 68.5, 68.2, 65.9, 61.3, 57.5, 56.5, 41.9, 39.5, 39.1, 36.8, 36.1, 34.3, 34.1,
33.7, 33.1, 32.9, 31.6, 30.9, 30.6, 29.7, 28.8, 26.7, 23.4, 22.8, 22.7, 22.0, 21.6,
21.3, 21.2, 21.1, 21.0, 20.0, 19.3, 18.8, 18.5, 18.2, 17.7, 16.3, 13.8, 11.5 ppm;
IR (neat): n˜ =3464, 2936, 1788, 1741, 1680, 1590, 1455, 1373, 1239, 1065,
1021 cmꢀ1
1245.6913, found: 1245.6958.
25: mixture of 24 (12.8 mg, 10.5 mmol, 1.00 equiv),
;
HRMS (ESI-TOF) calcd for C68H102O19 [M+Na]+ m/z=
A
4 (13.6 mg,
28: According to the method for the synthesis of 17, 27 (0.548 g,
1.80 mmol), 22 (1.41 g, 2.71 mmol) and MS-4ꢁ (2.71 g) in CH2Cl2
(18.0 mL) were treated with a mixture of 1.00m IBr in CH2Cl2 (3.60 mL,
3.60 mmol) and TBAB (1.45 g, 4.50 mmol) at 08C for 2 h. N,N-Diisopro-
pylethylamine (0.156 mL, 0.900 mmol) was then added to the reaction
mixture. Stirring for 20 h at the same temperature gave 28 (1.15 g,
1.74 mmol, 94%, b/a=94:6) after purification. The a,b isomers were sep-
arated by chromatography on silica gel with toluene/ethyl acetate 92:8.
½aꢁ2D8 =ꢀ13.88 (c=0.910, CHCl3); 1H NMR (400 MHz, CDCl3): d=8.19
(d, 2H, J=8.7 Hz), 7.39 (d, 2H, J=8.7 Hz), 5.28 (ddd, 1H, J=3.4 Hz, J=
3.4 Hz, J=3.4 Hz), 5.01 (dd, 1H, J=1.9 Hz, J=9.2 Hz), 4.96 (d, 1H, J=
3.9 Hz), 4.18 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 3.87 (dq, 1H, J=6.3 Hz, J=
9.2 Hz), 3.85 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.62 (ddd, 1H, J=5.3 Hz,
J=9.2 Hz, J=11.1 Hz), 3.47–3.43 (m, 2H), 3.35 (dd, 1H, J=3.4 Hz, J=
9.2 Hz), 3.22–3.32 (m, 5H), 2.36 (dd, 1H, J=5.3 Hz, J=13.0 Hz), 2.12 (s,
3H), 2.09 (ddd, 1H, J=1.9 Hz, J=3.4 Hz, J=14.5 Hz), 1.75 (ddd, 1H,
J=3.4 Hz, J=9.2 Hz, J=14.5 Hz), 1.56 (ddd, 1H, J=3.4 Hz, J=11.1 Hz,
J=13.0 Hz), 1.31 (d, 3H, J=6.3 Hz), 1.25 (d, 3H, J=6.3 Hz), 0.89 (s,
9H), 0.11 (s, 3H), 0.10 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=
170.1, 147.2, 145.4, 129.3, 124.1, 99.0, 92.8, 84.8, 79.5, 75.3, 70.2, 69.3, 66.7,
55.9, 51.6, 38.4, 35.0, 29.6, 25.8, 21.2, 18.4, 18.1, 17.6, ꢀ4.1, ꢀ5.1 ppm; IR
(solid): n˜ =2933, 2859, 1736, 1607, 1523, 1451, 1316, 1243, 1173, 1065,
1002 cmꢀ1; HRMS (ESI-TOF) calcd for C29H47NO12SSi [M+Na]+ m/z=
684.2486, found: 684.2490.
31.4 mmol) and pulverized activated MS-4ꢁ (30.0 mg) in dry toluene
(0.300 mL) was stirred at RT for 30 min under argon to remove a trace
amount of water. The reaction mixture was then cooled to ꢀ948C
(hexane–liquid N2 bath). After 5 min, a solution of iodine (9.29 mg,
36.6 mmol) in toluene (50.0 mL) and triisopropylsilane (0.430 mL,
2.09 mmol) was added to the reaction mixture. After being stirred for
1.5 h, the reaction mixture was neutralized with triethylamine at ꢀ948C
and filtered through Celite. Immediately the filtrate was poured into a
mixture of saturated aq. NaHCO3 and saturated aq. Na2S2O3, with cool-
ing. The aqueous layer was extracted with two portions of ethyl acetate.
The combined extract was washed with brine, dried over MgSO4, filtered,
and concentrated in vacuo. The residue was chromatographed on silica
gel with hexane/ethyl acetate 50:50 and further purified by gel permea-
tion chromatography (GPC) to give 25 (12.7 mg, 8.50 mmol, 81%, b/a=
94:6). The b/a ratio was determined by 1H NMR analysis (400 MHz).
½aꢁ2D5 =ꢀ4.218 (c=0.700, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.42
(brs, 1H), 5.39 (s, 1H), 5.39 (m, 1H), 5.22–5.26 (m, 2H), 5.15 (d, 1H, J=
9.7 Hz), 5.05 (dd, 1H, J=1.4 Hz, J=9.7 Hz), 4.92 (brd, 1H, J=2.9 Hz),
4.76 (m, 1H), 4.66 (brd, 1H, J=8.7 Hz), 4.54 (dd, 1H, J=2.9 Hz, J=
9.7 Hz), 4.10 (dd, 1H, J=2.9 Hz, J=11.1 Hz), 3.89 (dq, 1H, J=6.3 Hz,
J=9.7 Hz), 3.80 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.71 (m, 1H), 3.71 (m,
1H), 3.56 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.44 (ddd, 1H, J=4.8 Hz, J=
9.7 Hz, J=11.6 Hz), 3.36 (s, 3H), 3.26 (dd, 1H, J=2.9 Hz, J=9.7 Hz),
3.23 (dd, 1H, J=9.7 Hz, J=9.7 Hz), 3.20 (m, 1H), 2.40–2.84 (m, 8H),
2.28–2.39 (m, 3H), 2.22 (dd, 1H, J=4.8 Hz, J=13.0 Hz), 2.19 (m, 1H),
2.18 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 2.05 (m, 1H), 2.03 (s, 3H), 1.97 (s,
3H), 1.95 (q, 1H, J=7.7 Hz), 1.90 (m, 1H), 1.88 (q, 1H, J=7.7 Hz), 1.83
(q, 1H, J=7.7 Hz), 1.70–1.82 (m, 4H), 1.69 (s, 3H), 1.65 (s, 1H), 1.58 (s,
3H), 1.20–1.58 (m, 24H), 1.17 (d, 3H, J=6.3 Hz), 1.10 (s, 3H), 1.07 (d,
29: DBU was added to a stirred solution of 28 (1.12 g, 1.69 mmol) in
CH3CN (8.45 mL) (252 mL, 1.69 mmol) at 08C. After being stirred at RT
for 6 h, the reaction mixture was poured into saturated aq. NH4Cl. The
aqueous layer was extracted with two portions of ethyl acetate. The com-
bined extract was washed with 1m HCl, saturated aq. NaHCO3, and
Chem. Asian J. 2009, 4, 1114 – 1125
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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