Page 19 of 21
The Journal of Organic Chemistry
Na2SO4, filtered, and concentrated under reduced pressure to
15.8, 15.7, 14.86, 14.83, 14.7, 12.4, 11.8, 11.1, 11.0 (Six sig-
nals are missing due to overlap.); HRMS (ESI+) m/z: calcd. for
1
2
3
4
5
6
7
8
give a crude material, which was purified by preparative TLC
(CH2Cl2-acetone = 20:1) to afford a 3:2 mixture of 39 and its
C2’ epimer 40 (1.2 mg, 1.9 μmol, 48%) as a pale yellow solid
with recovery of β-hydroxy ester 52 (0.90 mg, 1.4 μmol, 36%).
Rf = 0.45 (CH2Cl2-acetone = 10:1); The physical data of 3:2
mixture of 39 and 40; IR (neat, cm–1): 3400, 2963, 2924, 2874,
2853, 1738, 1712, 1693, 1680, 1674, 1666, 1658, 1645, 1385,
C36H50N2O9S2Na 741.2855 [M+Na+], found 741.2835.
β-hydroxy ester 53. A screw cap test tube was charged with
the THP protected β-hydroxy ester S9 (4.0 mg, 5.6 μmol),
MeOH (28 μL), and CH2Cl2 (28 μL). To the solution was add-
ed PPTS (2.8 mg, 11 μmol). After stirring at 50 °C for 1.5 h,
the reaction mixture was diluted with CH2Cl2. The separated
organic layer was washed twice with 13.2% aqueous sodium
chloride, dried over Na2SO4, filtered, and concentrated under
reduced pressure to give a crude material, which was purified
by preparative TLC (CH2Cl2-acetone = 20:1) to afford β-
hydroxy ester 53 (2.7 mg, 4.3 μmol, 76%) as a pale yellow
solid. Rf = 0.34 (CH2Cl2-acetone = 10:1); [α]D22 –253 (c 0.530,
CHCl3); IR (neat, cm–1): 3468, 2962, 2924, 2876, 1732, 1693,
1
1339, 1194, 1126, 1003, 752; H NMR (600 MHz, CDCl3): δ
6.62–6.58 (m, 1H), 6.53 (s, 1H), 6.32 (dd, J = 8.4, 2.4 Hz,
0.6H), 6.29 (dd, J = 8.4, 2.4 Hz, 0.4H), 6.22 (dd, J = 8.4, 2.4
Hz, 1H), 5.92 (ddd, J = 8.4, 2.4, 2.4 Hz, 0.4H), 5.74 (ddd, J =
7.8, 2.4, 2.4 Hz, 0.6H), 5.27–5.22 (m, 0.6H), 5.12–5.08 (m,
0.4H), 4.95–4.92 (m, 1H), 4.92–4.88 (m, 1H), 4.72 (dd, J = 8.4,
1.8 Hz, 0.6H), 4.71–4.65 (m, 1H), 4.60 (dd, J = 8.4, 1.8 Hz,
0.4H), 4.49–4.44 (m, 0.6H), 4.42–4.37 (m, 0.4H), 3.72 (q, J =
7.2 Hz, 0.4H), 3.64 (q, J = 7.2 Hz, 0.6H), 3.13–2.98 (m, 4.4H),
2.90 (dq, J = 13.8, 6.6 Hz, 0.6H), 2.33–2.31 (m, 3H), 2.30 (s,
1.8H), 2.29 (s, 1.2H), 1.82 (ddd, J = 13.8, 8.4, 5.4 Hz, 0.4H),
1.67 (ddd, J = 13.2, 7.8, 6.0 Hz, 0.6H), 1.40 (d, J = 7.2 Hz,
1.8H), 1.40–1.24 (m, 3H), 1.33 (d, J = 7.2 Hz, 1.2H), 1.13 (d, J
= 7.2 Hz, 1.8H), 1.12 (d, J = 7.2 Hz, 1.2H), 1.11–1.03 (m, 1H),
0.92–0.84 (m, 6H); 13C NMR (150 MHz, CDCl3): δ 210.20,
210.17, 169.6, 169.3, 166.82, 166.79, 164.3, 164.2, 139.9,
139.6, 138.1, 138.0, 137.7, 110.8, 109.4, 109.3, 107.9, 107.8,
105.3, 105.0, 73.0, 72.62, 72.57, 71.9, 70.44, 70.38, 69.5, 69.4,
64.2, 64.1, 60.7, 60.4, 52.0, 50.4, 44.0, 43.3, 40.5, 40.4, 40.3,
40.2, 39.7, 32.1, 29.7, 29.5, 20.2, 19.52, 19.49, 17.3, 17.0,
14.91, 14.88, 14.77, 14.6, 13.0, 12.9, 11.2, 11.1 (Five signals
are missing due to overlap.); HRMS (ESI+) m/z: calcd. for
C31H40N2O8S2Na 655.2124 [M+Na+], found 655.2120.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
1680, 1666, 1651, 1393, 1384, 1337, 1192, 1128, 756; H
NMR (500 MHz, CDCl3): δ 6.61–6.57 (m, 1H), 6.54–6.51 (m,
1H), 6.31 (dd, J = 8.5, 2.5 Hz, 1H), 6.22 (dd, J = 8.0, 2.5 Hz,
1H), 5.79 (ddd, J = 8.0, 2.0, 2.0 Hz, 1H), 5.19 (d, J = 8.5 Hz,
1H), 4.93 (dd, J = 8.5, 2.0 Hz, 1H), 4.89 (d, J = 7.5 Hz, 1H),
4.71–4.66 (m, 1H), 4.64 (dd, J = 8.0, 2.0 Hz, 1H), 4.42 (d, J =
6.0 Hz, 1H), 3.67 (dd, J = 7.0, 6.0 Hz, 1H), 3.14–2.95 (m, 4H),
2.69 (ddd, J = 14.0, 7.5, 4.5 Hz, 1H), 2.30 (s, 3H), 2.29 (s, 3H),
1.68–1.59 (m, 1H), 1.50–1.37 (m, 2H), 1.27–1.19 (m, 1H), 1.22
(d, J = 7.0 Hz, 3H), 1.06–0.92 (m, 2H), 0.98 (d, J = 6.5 Hz,
3H), 0.88–0.83 (m, 6H); 13C NMR (125 MHz, CDCl3): δ 175.3,
166.8 164.3, 139.8, 138.00, 137.95, 137.6, 110.9, 109.6, 107.8,
105.6, 75.5, 72.6, 72.1, 70.4, 69.4, 64.1, 60.4, 42.3, 40.6, 40.4,
40.2, 33.3, 31.3, 28.1, 20.0, 15.1, 14.84, 14.80, 11.0, 10.9;
HRMS (ESI+) m/z: calcd. for C31H42N2O8S2Na 657.2280
[M+Na+], found 657.2268.
THP protected β-hydroxy ester S9. A screw cap test tube was
charged with 35 (14 mg, 31 μmol), 50 (8.9 mg, 31 μmol), and
CH2Cl2 (80 μL). To the solution was added DMAP (3.8 mg, 31
μmol) and WSCD·HCl (11.9 mg, 62.1 μmol) at 0 °C. After
stirring at reflux for 2 h, the reaction was quenched with 1 M
aqueous HCl. The resulting mixture was extracted with CH2Cl2
three times. The combined organic extracts were washed with
H2O and brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure. The residue was purified by prepara-
tive TLC (CH2Cl2-acetone = 20:1) to afford the desired THP
protected β-hydroxy ester S9 (8.0 mg, 11 μmol, 36%) as a pale
yellow solid with recovery of 35 (7.0 mg, 16 μmol, 50%). Rf =
β-Keto ester 40. A screw cap test tube was charged with the β-
hydroxy ester 53 (2.7 mg, 4.3 μmol) and dry CH2Cl2 (70 μL).
To the solution was added Dess-Martin periodinane (2.1 mg,
8.5 μmol) at 0 °C. After stirring at 0 °C for 1.5 h, the reaction
mixture was diluted with CH2Cl2. The separated organic layer
was washed with saturated aqueous NaHCO3 and brine, dried
over Na2SO4, filtered, and concentrated under reduced pressure
to give a crude material, which was purified by preparative
TLC (CH2Cl2-acetone = 10:1) to afford a 5:1 mixture of β-keto
ester 40 and its C2’ epimer, 39 (1.0 mg, 1.6 μmol, 37%) as a
pale yellow solid with recovery of the β-hydroxy ester 53 (1.2
mg, 1.9 μmol, 44%). The physical data of a 5:1 mixture of 39
27
0.41 (CH2Cl2-acetone = 10:1); [α]D –229 (c, 0.515, CHCl3);
27
and 40; Rf = 0.43 (CH2Cl2-acetone = 10:1); [α]D –246 (c
IR (neat, cm–1): 3400, 2957, 2928, 2874, 1732, 1693, 1681,
1666, 1658, 1651, 1385, 1198, 1128, 1026, 754, 667; 1H NMR
(500 MHz, CDCl3): δ 6.61–6.57 (m, 1H), 6.54–6.49 (m, 1H),
6.33–6.25 (m, 1H), 6.22–6.18 (m, 1H), 5.90 (ddd, J = 8.0, 2.5,
2.5 Hz, 0.4H), 5.88 (ddd, J = 8.0, 2.5, 2.5 Hz, 0.6H), 5.23–5.10
(m, 1H), 4.93 (dd, J = 8.0, 2.0 Hz, 0.6H), 4.92–4.85 (m, 1H),
4.83 (dd, J = 8.0, 2.0 Hz, 0.4H), 4.70–4.63 (m, 1.2H), 4.62–
4.57 (m, 0.8H), 4.42 (br s, 1H), 3.95–3.84 (m, 1H), 3.84–3.80
(m, 1H), 3.48–3.42 (m, 0.5H), 3.42–3.36 (m, 0.5H), 3.14–2.95
(m, 4H), 2.75–2.65 (m, 1H), 2.30–2.26 (m, 6H), 1.85–1.75 (m,
1H), 1.75–1.65 (m, 3H), 1.65–1.42 (m, 6H), 1.42–1.33 (m, 1H),
1.23 (d, J = 7.0 Hz, 1.2H), 1.17 (d, J = 7.0 Hz, 1.8H), 1.10–
0.93 (m, 2H), 0.96 (d, J = 7.0 Hz, 1.8H), 0.94 (d, J = 7.0 Hz,
1.2H), 0.90–0.78 (m, 7H); 13C NMR (125 MHz, CDCl3): δ
175.0, 174.4, 167.0, 166.9, 164.10, 164.07, 139.8, 139.4,
137.95, 137.86, 137.82, 137.61, 137.57, 110.8, 109.6, 109.5,
108.0, 107.9, 105.9, 105.6, 100.5, 99.4, 83.1, 81.1, 72.6, 71.5,
71.2, 70.51, 70.48, 64.12, 64.10, 63.2, 63.0, 60.7, 60.5, 41.8,
41.4, 41.1, 41.0, 40.6, 40., 40.4, 40.2, 34.4, 34.0, 31.7, 31.5,
30.95, 30.93, 28.9, 28.4, 25.44, 25.40, 20.2, 20.1, 20.0, 19.6,
0.210, CHCl3); IR (neat, cm–1): 3400, 2963, 2926, 2876, 1747,
1713, 1693, 1682, 1666, 1651, 1634, 1396, 1385, 1194, 1124,
1003, 754; 1H NMR (600 MHz, CDCl3): δ 6.60 (s, 1H), 6.53 (s,
1H), 6.29 (dd, J = 8.4, 2.4 Hz, 1H), 6.22 (dd, J = 8.4, 2.4 Hz,
1H), 5.96–5.92 (m, 1H), 5.14–5.09 (m, 1H,), 4.94 (dd, J = 8.4,
1.2 Hz, 1H), 4.93–4.87 (d, J = 7.8 Hz, 1H), 4.71–4.65 (m, 1H),
4.61 (dd, J = 8.4, 1.8 Hz, 1H), 4.39 (br s, 1H), 3.72 (q, J = 7.2
Hz, 1H), 3.14–2.98 (m, 5H), 2.31 (s, 3H), 2.29 (s, 3H), 1.87–
1.79 (m, 1H), 1.43–1.25 (m, 2H), 1.33 (d, J = 7.2 Hz, 3H),
1.19–1.03 (m, 5H), 0.96–0.84 (m, 6H); 13C NMR (150 MHz,
CDCl3): δ 210.2, 169.3, 166.8, 164.3, 139.9, 138.1, 138.0,
137.6, 110.8, 109.4, 107.9, 105.0, 72.6, 71.9, 70.4, 69.5, 64.1,
60.7, 50.4, 44.0, 40.5, 40.2, 39.7, 32.1, 29.5, 19.5, 17.3, 14.9,
14.6, 13.0, 11.2; HRMS (ESI+) m/z: calcd. for C31H40N2O8S2Na
655.2124 [M+Na+], found 655.2123.
THP protected β-hydroxy ester 55. A screw cap test tube was
charged with (–)-deacetylaranotin (5) (4.3 mg, 10 μmol), THP
protected β-hydroxy carboxylic acid 54 (2.3 mg, 8.2 μmol),
and CH2Cl2 (200 μL). To the solution was added DMAP (1.2
ACS Paragon Plus Environment