Wennekes et al.
CH2 pentyl, CH2 butyl), 1.30 (m, 2H, CH2 butyl), 0.94 (t, JH-H
)
2900.7, 2846.7, 1666.4, 1458.1, 1365.5, 1249.8, 1103.2, 1041.5,
7.4 Hz, 3H, CH3 butyl). 13C NMR (100 MHz, CD3OD, HMQC):
δ 83.0 (OCH2-adamantane), 79.6, 79.2 (C-2, C-3), 72.6 (OCH2
pentyl), 72.1 (C-4), 71.7 (OCH2 pentyl), 67.1 (C-5), 59.4 (C-6),
55.2 (C-1), 53.6 (NCH2 butyl), 40.9 (3×CH2 adamantane), 38.4
(3×CH2 adamantane), 35.1 (Cq adamantane), 31.0, 30.7 (2×CH2
pentyl), 29.8 (3×CH adamantane), 27.3 (CH2 butyl), 23.9 (CH2
pentyl), 21.8 (CH2 butyl), 14.4 (CH3 butyl). ATR-IR (thin film):
3371.3, 2900.7, 2846.7, 2090.7, 1689.5, 1458.1, 1365.5, 1149.5,
902.6, 817.8 cm-1. [R]20 -2.5° (c 0.40, CHCl3/MeOH, 1:1).
D
HRMS: found 454.3539 [M + H]+, calcd for [C26H47NO5 + H]+
454.3527.
3-O-[5-(Adamantane-1-yl-methoxy)-pentyl]-1-deoxynojirimy-
1
cin (14): H NMR (400 MHz, CDCl3/CD3OD, 2:1, COSY): δ
3.93-3.80 (m, 4H, CH2-6, OCH2 pentyl), 3.76 (m, 1H, H-2), 3.57
(dd, JH-H ) 9.1 Hz, 1H, H-4), 3.42 (t, JH-H ) 6.5 Hz, 2H, OCH2
pentyl), 3.31 (dd, JH1a-H2 ) 4.4 Hz, JH1a-H1b ) 12.4 Hz, 1H, H-1a),
3.19 (m, 1H, H-3), 2.99 (s, 2H, OCH2-adamantane), 2.98 (m, 1H,
H-5), 2.78 (dd, JH-H ) 11.9 Hz, 1H, H-1b), 1.96 (br s, 3H, 3×CH
adamantane), 1.75-1.57 (m, 10H, 3×CH2 adamantane, 2×CH2
pentyl), 1.54 (br d, JH-H ) 2.3 Hz, 6H, 3×CH2 adamantane), 1.42
(m, 2H, CH2-3′ pentyl). 13C NMR (100 MHz, CDCl3/CD3OD,
2:1): δ 84.2, 81.5, 72.8, 71.2, 67.7, 67.0, 60.3, 57.7, 46.0, 39.1,
36.6, 33.6, 29.4, 28.7, 27.8, 21.9. ATR-IR (thin film): 3357.8,
2900.7, 2846.7, 1674.1, 1596.9, 1448.4, 1344.3, 1186.1, 1103.2,
1103.2, 902.6, 825.5, 663.5 cm-1. [R]20 +28.1° (c 0.32, CHCl3/
D
MeOH, 2:1). HRMS: found 454.3551 [M + H]+, calcd for [C26H47-
NO5 + H]+ 454.3527.
4-O-[5-(Adamantane-1-yl-methoxy)-pentyl]-1-deoxynojirimy-
cin (11): 1H NMR (400 MHz, CD3OD, COSY): δ 3.89-3.85 (m,
1H, OCHH pentyl), 3.79 (dd, JH-H ) 2.5 Hz, JH-H ) 10.8 Hz,
1H, H-6a), 3.62-3.52 (m, 2H, H-6b, OCHH pentyl), 3.42-3.36
(m, 3H, H-2, OCH2 pentyl), 3.28 (dd, JH-H ) 9.2 Hz, 1H, H-3),
3.07 (dd, JH1a-H2 ) 5.1 Hz, JH1a-H1b ) 12.2 Hz, 1H, H-1a), 3.00
(dd, JH-H ) 9.6 Hz, 1H, H-4), 2.96 (s, 2H, OCH2-adamantane),
2.47 (ddd, JH-H ) 2.5 Hz, JH-H ) 5.6 Hz, JH-H ) 9.6 Hz, 1H,
H-5), 2.40 (dd, JH1b-H2 ) 10.8 Hz, JH1b-H1a ) 12.2 Hz, 1H, H-1b),
1.94 (br s, 3H, 3×CH adamantane), 1.77-1.66 (m, 6H, 3×CH2
adamantane), 1.64-1.55 (m, 10H, 3×CH2 adamantane, 2×CH2
pentyl), 1.43 (m, 2H, CH2-3′ pentyl). 13C NMR (100 MHz, CD3-
OD, HMQC): δ 83.0 (OCH2-adamantane), 81.2 (C-4), 80.6 (C-3),
72.8 (C-2), 73.9, 72.6 (2×OCH2 pentyl), 62.4 (C-6), 62.3 (C-5),
50.8 (C-1), 40.4 (3×CH2 adamantane), 38.3 (3×CH2 adamantane),
35.1 (Cq adamantane), 31.2, 30.5 (2×CH2 pentyl), 29.7 (3×CH
adamantane), 23.9 (CH2-3′ pentyl). ATR-IR (thin film): 3371.3,
2900.7, 2846.7, 2476.4, 2067.5, 1674.1, 1450.4, 1365.5, 1257.5,
1026.1, 732.9, 623.0 cm-1. [R]20 +17.4° (c 0.46, MeOH).
D
HRMS: found 398.2892 [M + H]+, calcd for [C22H39NO5 + H]+
398.2901.
N-Methyl-3-O-[5-(adamantane-1-yl-methoxy)-pentyl]-1-deox-
ynojirimycin (15): 1H NMR (600 MHz, CD3OD): δ 4.04 (d,
JH6a-H6b ) 12.2 Hz, 1H), 3.88 (dd, JH6b-H6a ) 12.2 Hz, JH6b-H5
)
2.7 Hz, 1H), 3.85 (m, 2H), 3.70 (m, 1H), 3.60 (dd, JH-H ) 9.7 Hz,
1H), 3.38 (t, JH-H ) 6.4 Hz, 2H), 3.32 (dd, JH1a-H2 ) 4.7 Hz,
JH1a-H1b ) 12.1 Hz, 1H), 3.15 (dd, JH-H ) 9.2 Hz, 1H), 2.96 (s,
2H), 2.95-2.83 (m, 5H), 1.93 (br s, 3H), 1.76-1.63 (m, 8H), 1.60-
1.55 (m, 8H), 1.44 (m, 2H). 13C NMR (150 MHz, CD3OD): δ
86.6, 83.1, 74.5, 72.7, 69.3, 68.7, 68.0, 58.9, 41.3, 40.8, 38.3, 35.2,
31.1, 30.5, 29.7, 23.7. ATR-IR (thin film): 3350.7, 2902.7, 2846.7,
1195.8, 1095.5, 1049.2, 979.8, 879.5, 840.9, 717.5 cm-1. [R]20
1656.7, 1454.2, 1357.8, 1101.3, 1039.6, 1020.3, 958.6, 611.4 cm-1
.
D
+16.9° (c 1.08, MeOH). HRMS: found 398.2905 [M + H]+, calcd
[R]20D +6.9° (c 0.58, MeOH). HRMS: found 412.3047 [M + H]+,
for [C22H39NO5 + H]+ 398.2901.
calcd for [C23H42NO5 + H]+ 412.3058.
N-Methyl-4-O-[5-(adamantane-1-yl-methoxy)-pentyl]-1-deox-
ynojirimycin (12): 1H NMR (400 MHz, CD3OD, COSY): δ 3.94-
3.89 (m, 1H, OCHH pentyl), 3.82 (dd, JH6a-H5 ) 2.3 Hz, JH6a-H6b
N-Butyl-3-O-[5-(adamantane-1-yl-methoxy)-pentyl]-1-deox-
ynojirimycin (16): 1H NMR (600 MHz, CD3OD/acetone-d6, 3:1):
δ 4.09 (m, 1H), 3.90 (m, 1H), 3.83 (m, 2H), 3.77 (m, 1H), 3.66
(m, 1H), 3.43 (m, 1H), 3.38 (m, 3H), 3.24-3.20 (m, 2H, H-3),
3.09 (m, 1H), 3.01 (m, 1H), 2.96 (s, 2H), 1.94 (br s, 3H), 1.76-
) 11.9 Hz, 1H, CH-6a), 3.74 (dd, JH6b-H5 ) 2.1 Hz, JH6b-H6a
)
11.9 Hz, 1H, CH-6b), 3.65-3.60 (m, 1H, OCHH pentyl), 3.47 (m,
1H, H-2), 3.38 (t, JH-H ) 6.3 Hz, 2H, OCH2 pentyl), 3.23-3.21
(m, 2H, H-3, H-4), 2.96 (s, 2H, OCH2-adamantane), 2.89 (dd, JH-H
) 4.8 Hz, JH-H ) 11.1 Hz, 1H, H-1a), 2.33 (s, 3H, NCH3), 2.03
(dd, JH-H ) 10.8 Hz, 1H, H-1b), 1.93 (br s, 3H, 3×CH adaman-
tane), 1.76-1.65 (m, 7H, H-5, 3×CH2 adamantane), 1.63-1.55
(m, 10H, 3×CH2 adamantane, 2×CH2 pentyl), 1.44 (m, 2H, CH2-
3′ pentyl). 13C NMR (100 MHz, CD3OD): δ 83.1, 80.7, 79.5, 74.1,
72.6, 70.7, 69.8, 62.1, 58.5, 42.3, 40.8, 38.3, 35.2, 31.2, 30.6, 29.6,
23.9. ATR-IR (thin film): 3386.8, 2900.7, 2846.7, 2792.7, 2106.1,
1666.4, 1458.1, 1357.8, 1249.8, 1095.5, 1041.5, 987.5, 918.1, 825.5
1.64 (m, 10H), 1.58-1.55 (m, 8H), 1.43 (m, 4H), 1.00 (t, JH-H
)
7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3/CD3OD, 2:1): δ 81.6,
71.3, 66.8, 65.8, 39.2, 36.7, 33.7, 29.5, 28.8, 27.9, 22.0, 19.4, 12.8.
ATR-IR (thin film): 3340.5, 2902.7, 2846.7, 1672.2, 1456.2,
1363.6, 1103.2, 1029.9, 1029.9, 607.5 cm-1. [R]20D +2.8° (c 0.50,
MeOH). HRMS: found 454.3510 [M + H]+, calcd for [C26H47-
NO5 + H]+ 454.3527.
(1S)-1-C-[5-(Adamantan-1-yl-methoxy)-pentyl]-1-deoxynojiri-
1
mycin (17). H NMR (300 MHz, CD3OD, COSY): δ 3.91 (dd,
JH6a-H5 ) 3.0 Hz, JH6a-H6b ) 10.9 Hz, 1H, H-6a), 3.49 (dd, JH6b-H5
) 7.8 Hz, JH6b-H6a ) 10.9 Hz, 1H, H-6b), 3.38 (t, JH-H ) 6.4 Hz,
2H, OCH2-5′ pentyl), 3.19 (dd, JH-H ) 8.9 Hz, 1H, H-3), 3.10
(dd, JH-H ) 9.1 Hz, 1H, H-4), 3.00-2.96 (m, 3H, H-2, OCH2-
adamantane), 2.53 (m, 1H, H-5), 2.41 (m, 1H, H-1), 1.95-1.85
(m, 5H, 3×CH adamantane, CH2 pentyl), 1.76-1.66 (m, 6H,
3×CH2 adamantane), 1.58-1.50 (m, 8H, 3×CH2 adamantane, CH2
pentyl), 1.45-1.25 (m, 4H, 2×CH2 pentyl). 13C NMR (75 MHz,
CD3OD, HMQC): δ 83.1 (OCH2-adamantane), 79.1 (C-3), 74.2
(C-2), 72.5 (OCH2-5′ pentyl), 70.4 (C-4), 62.2 (C-5), 60.7 (C-1),
60.1 (C-6), 40.8 (3×CH2 adamantane), 38.3 (3×CH2 adamantane),
35.2 (Cq adamantane), 31.7, 30.5 (2×CH2 pentyl), 27.8 (3×CH
adamantane), 27.4, 26.7 (2×CH2 pentyl). ATR-IR (thin film):
3309.6, 2900.7, 2846.7, 1450.4, 1365.5, 1311.5, 1257.5, 1149.5,
1095.5, 1018.3, 910.3, 825.5, 732.9, 671.2 cm-1. [R]20D -12.5° (c
0.40, CHCl3). HRMS: found 398.2905 [M + H]+, calcd for
[C22H39NO5 + H]+ 398.2901.
cm-1. [R]20 +11.5° (c 0.35, CHCl3/MeOH, 2:1). HRMS: found
D
412.3074 [M + H]+, calcd for [C23H42NO5 + H]+ 412.3058.
N-Butyl-4-O-[5-(adamantane-1-yl-methoxy)-pentyl]-1-deox-
1
ynojirimycin (13): H NMR (400 MHz, CD3OD): δ 3.94-3.89
(m, 1H, OCHH pentyl), 3.83 (dd, JH6a-H5 ) 2.1 Hz, JH6a-H6b
)
11.8 Hz, 1H, CH-6a), 3.75 (dd, JH6b-H5 ) 2.2 Hz, JH6b-H6a ) 11.8
Hz, 1H, CH-6b), 3.65-3.59 (m, 1H, OCHH pentyl), 3.44 (ddd,
JH-H ) 4.7 Hz, JH-H ) 10.0 Hz, JH-H ) 14.6 Hz, 1H, H-2), 3.38
(t, JH-H ) 6.3 Hz, 2H, OCH2 pentyl), 3.24-3.19 (m, 2H, H-3,
H-4), 2.97-2.93 (m, 3H, H-1a, OCH2-adamantane), 2.76 (m, 1H,
NCHH butyl), 2.58 (m, 1H, NCHH butyl), 2.15-2.07 (m, 2H, H-1b,
H-5), 1.94 (br s, 3H, 3×CH adamantane), 1.77-1.55 (m, 16H,
6×CH2 adamantane, 2×CH2 pentyl), 1.48-1.41 (m, 4H, CH2
pentyl, CH2 butyl), 1.30 (m, 2H, CH2 butyl), 0.94 (t, JH-H ) 7.2
Hz, 3H, CH3 butyl). 13C NMR (100 MHz, CD3OD, HMQC): δ
83.0 (OCH2-adamantane), 80.7, 79.9 (C-3, C-4), 74.0, 72.6
(2×OCH2 pentyl), 71.0 (C-2), 66.6 (C-5), 58.5 (C-6), 57.5 (C-1),
53.3 (NCH2 butyl), 40.8 (3×CH2 adamantane), 38.3 (3×CH2
adamantane), 35.2 (Cq adamantane), 31.2, 30.6 (2×CH2 pentyl),
29.8 (3×CH adamantane), 27.3 (CH2 butyl), 23.9 (CH2 pentyl),
21.8 (CH2 butyl), 14.4 (CH3 butyl). ATR-IR (thin film): 3363.6,
(1S)-N-Methyl-1-C-[5-(adamantan-1-yl-methoxy)-pentyl]-1-
deoxynojirimycin (18): 1H NMR (400 MHz, CD3OD, COSY): δ
3.90 (dd, JH6a-H6b ) 11.8 Hz, JH6a-H5 ) 3.0 Hz, 1H, H-6a), 3.82
(dd, JH6b-H6a ) 11.8 Hz, JH6b-H5 ) 3.9 Hz, 1H, H-6b), 3.40-3.35
(m, 3H, H-3, OCH2-5′ pentyl), 3.22 (dd, JH-H ) 9.3 Hz, 1H, H-2),
1096 J. Org. Chem., Vol. 72, No. 4, 2007