Vol. 64, No. 7 (2016)
Chem. Pharm. Bull.
877
q, quartet; m, multiplet; br, broaden peak. The numbering of
Acetate 16 Ac O (130µL, 1.4mmol) was added to a solu-
2
compounds corresponds to that of ryanodine (1). High resolu- tion of benzyl ether 15 (7.9mg, 14µmol) and DMAP (5mg,
tion (HR)-MS were measured JEOL JMS-T100LP. 40µmol) in pyridine (1.4mL) at room temperature. After
Boronate 10 A solution of (+)-ryanodol (2, 8.2mg, being stirred for 1h at room temperature, the reaction mix-
0µmol) and PhB(OH) (7.5mg, 61µmol) in benzene (1mL) ture was quenched with saturated aqueous NaHCO (5mL) at
2
2
3
and MeOH (1mL) was stirred for 5min at room temperature. 0°C. The resultant solution was extracted with CHCl –i-PrOH
3
The reaction mixture was concentrated. The residue was 3:1 (5mL×7). The combined organic layers were dried over
loaded on PTLC for 40h at room temperature to complete the Na SO and concentrated. The residue was purified by PTLC
2
4
conversion to boronate 10. Then, the PTLC was developed on silica gel (CHCl –MeOH 50:1, ×2) to afford acetate 16
3
(
CHCl –MeOH 10:1) to obtain boronate 10 (9.1mg, 19µmol) (5.0mg, 8.1µmol) in 59% yield: colorless solid; mp 91–92°C;
3
2
3
24
in 91% yield: colorless solid; mp >300°C; [α]D −25 (c=0.46, [α]D +16 (c=0.25, MeOH); IR (film) 3502, 2962, 2931, 2876,
MeOH); IR (film) 3366, 2955, 2925, 2854, 1736, 1714, 1458, 1718, 1331, 1254, 1127cm ; H-NMR (400MHz, CD OD)
1
−1
1
3
−1
1
375, 1259cm ; H-NMR (400MHz, CD OD) δ: 1.045 (3H, δ: 0.90 (3H, d, J=6.3Hz, H21), 1.03 (3H, d, J=6.8Hz, H18),
3
d, J=6.3Hz, H18) 1.049 (3H, d, J=6.3Hz, H21), 1.08 (3H, s, 1.08 (3H, d, J=6.8Hz, H19), 1.11 (3H, s, H20), 1.36 (3H,
H20), 1.12 (3H, d, J=6.8Hz, H19), 1.33 (3H, s, H17), 1.41 (1H, s, H17), 1.50 (1H, ddd, J=12.7, 4.1, 2.3Hz, H7a), 1.74 (1H,
ddd, J=12.7, 4.1, 2.3Hz, H7a), 1.66 (1H, dddd, J=12.2, 5.0, dddd, J=13.1, 5.0, 4.5, 2.3Hz, H8a), 1.86 (1H, dddd, J=13.1,
4
.5, 2.3Hz, H8a), 1.75 (1H, dddd, J=12.2, 12.2, 12.2, 4.1Hz, 12.7, 12.7, 4.1Hz, H8b), 2.04 (3H, s, COCH ), 2.05 (1H, ddqd,
3
H8b), 1.83 (1H, ddqd, J=12.2, 10.0, 6.3, 4.5Hz, H9), 1.92 (1H, J=12.7, 10.9, 6.3, 4.5Hz, H9), 2.07 (1H, ddd, J=12.7, 12.7,
d, J=13.1Hz, H14a), 2.03 (1H, ddd, J=12.7, 12.2, 5.0Hz, H7b), 5.0Hz, H7b), 2.23 (1H, qq, J=6.8, 6.8Hz, H13), 2.35 (1H,
2
.24 (1H, qq, J=6.8, 6.3Hz, H13), 2.59 (1H, d, J=13.1Hz, d, J=13.6Hz, H14a), 2.44 (1H, d, J=13.6Hz, H14b), 4.38
H14b), 3.65 (1H, d, J=10.0Hz, H10), 4.42 (1H, s, H3), 7.32 (1H, s, H3), 4.76 (1H, d, J=11.3Hz, PhCH H ), 4.80 (1H, d,
A
B
(
2H, ddd, J=7.3, 7.3, 0.9Hz, m-H C H B), 7.42 (1H, tt, J=7.3, J=11.3Hz, PhCH H ), 5.16 (1H, d, J=10.9Hz, H10), 7.27 (1H,
2 6 3 A B
1
.4Hz, p-HC H B), 7.78 (2H, dd, J=7.3, 1.4Hz, o-H C H B); tt, J=6.3, 1.4Hz, p-HC H CH ), 7.30–7.42 (6H, m, aromatic),
6 4 2 6 3 6 4 2
1
3
C-NMR (100MHz, CD OD) δ: 10.2, 13.6, 19.0, 19.4, 19.5, 7.43 (1H, tt, J=6.3, 1.4Hz, p-HC H B), 7.81 (2H, dd, J=8.2,
3
6
4
13
2
5.7, 29.4, 30.9, 35.4, 40.9, 46.9, 64.6, 72.6, 85.5, 87.3, 88.2, 1.4Hz, o-H C H B); C-NMR (100MHz, CD OD) δ: 10.6,
2 6 3 3
89.0, 92.5, 97.2, 103.7, 128.5 (2C), 131.9, 135.1 (2C) (ipso car- 13.9, 18.4, 19.36, 19.39, 21.4, 25.8, 29.1, 31.1, 34.4, 36.3, 46.8,
bon peak of phenyl boronate was not observed); HR-MS (elec- 66.5, 67.0, 74.1, 85.6, 87.8, 88.1, 88.5, 92.7, 96.6, 106.8, 128.37,
+
trospray ionization (ESI)) Calcd for C H BNaO [M+Na]
128.44 (2C), 128.5 (2C), 129.2 (2C), 131.9, 135.2 (2C), 140.2,
172.8 (ipso carbon peak of phenyl boronate was not observed);
2
6
35
8
509.2317. Found 509.2324.
Benzyl Ether 15 NaH in mineral oil (purity 50–72%) was HR-MS (ESI) Calcd for C H BNaO [M+Na]+ 641.2892.
washed with n-hexane, and dried in vacuo. The purified NaH Found 641.2899.
35
43
9
(18mg, 0.76mmol) was added to a solution of boronate 10
Bis-boronate 17 PhB(OH) (10mg, 82µmol) was added
2
(7.4mg, 15µmol) in DMF (1.5mL) at –40°C. After the resul- to a solution of acetate 16 (5.0mg, 8.1µmol) in benzene
tant mixture was stirred for 10min at the same temperature, (2mL). The reaction mixture was stirred for 5min at room
BnCl (18µL, 0.15mmol) was added. The reaction mixture was temperature, and then concentrated. The crude was dissolved
stirred for 20h at −15°C. The reaction was quenched with sat- in benzene (2mL) and concentrated three times to complete
urated aqueous NH Cl (2mL). The resultant solution was ex- the boronate formation. The residue was purified by PTLC
4
tracted with CHCl –i-PrOH 3:1 (3mL×7), and the combined on silica gel (CHCl –MeOH 50:1) to afford bis-boronate 17
3
3
organic layers were dried over Na SO and concentrated. The (3.6mg, 5.1µmol) in 63% yield: colorless solid; mp 93–94°C;
2
4
2
7
residue was purified by PTLC on silica gel (CHCl –MeOH [α] −32 (c=0.18, CHCl ); IR (film) 3491, 2962, 2930, 2877,
0:1) to afford benzyl ether 15 (7.9mg, 14µmol) in 90% yield: 1719, 1335, 1250, 1094cm ; H-NMR (400MHz, CDCl3)
colorless solid; mp 96–97°C; [α]D −0.43 (c=0.40, MeOH); IR δ: 0.96 (3H, d, J=6.8Hz, H21), 1.13 (3H, s, H20), 1.28 (3H,
film) 3446, 2960, 2928, 2876, 1455, 1440, 1360, 1330cm ; d, J=6.8Hz, H18), 1.29 (3H, d, J=6.8Hz, H19), 1.34 (3H,
H-NMR (400MHz, CD OD) δ: 1.05 (3H, d, J=6.3Hz, H18), s, H17), 1.57 (1H, m, H7a), 1.77 (1H, m, H8a), 1.84 (3H, s,
.06 (3H, d, J=6.3Hz, H21), 1.09 (3H, d, J=6.8Hz, H19), 1.11 COCH ), 1.93 (1H, dddd, J=12.7, 12.7, 12.7, 4.1Hz, H8b),
3H, s, H20), 1.39 (3H, s, H17), 1.46 (1H, ddd, J=12.7, 4.1, 2.08 (1H, m, H9), 2.08 (1H, ddd, J=12.7, 12.7, 4.5Hz, H7b),
.3Hz, H7a), 1.70 (1H, dddd, J=12.7, 5.0, 4.5, 2.3Hz, H8a), 2.19 (1H, qq, J=6.8, 6.8Hz, H13), 2.20 (1H, d, J=6.3Hz,
3
D
3
−1
1
1
2
4
−1
(
1
3
1
(
2
1
3
.77 (1H, dddd, J=12.7, 12.7, 12.2, 4.1Hz, H8b), 1.90 (1H, OH), 2.42 (1H, d, J=13.6Hz, H14a), 2.85 (1H, d, J=13.6Hz,
ddqd, J=12.7, 10.4, 6.3, 4.5Hz, H9), 2.04 (1H, ddd, J=12.7, H14b), 4.66 (1H, d, J=6.3Hz, H3), 4.79 (1H, d, J=11.3Hz,
1
2.2, 5.0Hz, H7b), 2.25 (1H, qq, J=6.8, 6.3Hz, H13), 2.34 PhCH H ), 4.89 (1H, d, J=11.3Hz, PhCH H ), 5.42 (1H, d,
A B A B
(
1H, d, J=13.1Hz, H14a), 2.43 (1H, d, J=13.1Hz, H14b), J=10.9Hz, H10), 7.28–7.46 (11H, m, aromatic), 7.72–7.80 (4H,
13
3
.68 (1H, d, J=10.4Hz, H10), 4.44 (1H, s, H3), 4.75 (1H, d, m, aromatic); C-NMR (100MHz, CDCl ) δ: 10.3, 13.1, 17.0,
3
J=11.8Hz, PhCH H ), 4.80 (1H, d, J=11.8Hz, PhCH H ), 17.4, 17.8, 21.1, 24.7, 27.9, 31.6, 32.9, 35.3, 45.6, 62.8, 65.9, 71.7,
A
B
A
B
7.25 (1H, tt, J=6.3, 1.4Hz, aromatic), 7.30–7.40 (6H, m, aro- 85.3, 85.6, 87.6, 90.9, 93.9, 96.3, 105.8, 127.0 (2C), 127.4, 127.5
matic), 7.42 (1H, tt, J=6.3, 1.4Hz, p-HC H B), 7.78 (2H, dd, (2C), 127.6 (2C), 128.3 (2C), 131.07, 131.14, 134.2 (2C), 134.4
6
4
13
J=7.7, 1.4Hz, o-H C H B); C-NMR (100MHz, CD OD) δ: (2C), 138.2, 170.0 (two ipso carbon peaks of phenyl boronate
2
6
3
3
1
6
0.5, 13.8, 19.0, 19.4 (2C), 25.8, 29.4, 31.1, 35.4, 36.4, 46.9, were not observed); HR-MS (ESI) Calcd for C H B NaO
41
46
2
9
+
6.3, 66.9, 72.6, 85.5, 88.0, 88.2, 88.9, 92.5, 97.2, 106.7, 128.3 [M+Na] 727.3220. Found 727.3236.
(3C), 128.5 (2C), 129.2 (2C), 131.9, 135.1 (2C), 140.2 (ipso car-
Glycine Ester 18 2,4,6-Trichlorobenzoyl chloride (24µL,
bon peak of phenyl boronate was not observed); HR-MS (ESI) 0.15mmol) was added to a suspension of bis-boronate 17
+
Calcd for C H BNaO [M+Na] 599.2787. Found 599.2794.
(3.6mg, 5.1µmol), N,N-Boc -glycine (A, 28mg, 0.10mmol),
2
33
41
8