8
Tetrahedron
20
o
Pale yellow solid, mp: 58-60 C, 0.81 g, yie
A
ld
C
5
C
2%
E
,
P
[α
T
]
ED
=
MA
1
N
.50
U
-1
S
.65
C
(
R
m,
I
1
P
H
T
in CH ), 1.72-1.85 (m, 1H in CH ), 2.28 (s, 3H,
2 2
D
1
+
8.8 (c 1.0, CHCl ). H NMR (400 MHz, CDCl ) δ: 0.87 (d, J =
CH ), 2.67-2.81 (m, 3H, CH & 1H in CH S), 2.93-3.00 (m, 1H
3
3
3
2
2
6
.8 Hz, 3H, CH ), 0.90 (d, J = 6.8 Hz, 3H, CH ), 1.56 (dheptet, J
in CH S), 3.80-3.95 (m, 1H, CHN), 4.75 (d, J = 8.4 Hz, 1H, NH),
3
3
2
=
4.4, 6.8 Hz, 1H, CH), 1.70-1.82 (m, 2H, CH ), 2.31 (s, 3H,
5.01 (s, 2H, CH O), 5.04 (d, J = 12.4 Hz, 1H in CH O), 5.08 (d,
2
2
2
CH ), 2.78 (ddd, J = 13.6, 8.8, 7.2 Hz, 1H in CH S), 2.98 (ddd, J
J = 12.4 Hz, 1H in CH O), 6.87 (d, J = 8.4 Hz, 2H, ArH), 7.04 (d,
2
13
3
2
=
13.6, 8.8, 4.8 Hz, 1H in CH S), 3.54-3.62 (m, 1H, CHN), 4.62
J = 8.4 Hz, 2H, ArH), 7.27-7.45 (m, 10H, ArH). C NMR (100
2
(
d, J = 9.6 Hz, 1H, NH), 5.08 (d, J = 12.0 Hz, 1H in CH O), 5.11
MHz, CDCl ) δ: 25.8, 30.5, 34.1, 40.1, 51.7, 66.5, 69.9, 114.8,
2
3
1
3
(d, J = 12.0 Hz, 1H in CH O), 7.30-7.39 (m, 5H, ArH). C NMR
127.4, 127.8, 127.9, 128.0, 128.4, 128.5, 129.6, 130.3, 136.5,
2
-
1
(100 MHz, CDCl ) δ: 17.6, 18.9, 26.2, 30.6, 32.2, 32.7, 55.7,
137.0, 155.9, 157.5, 195.8. IR (vmax, cm ) 3347, 3032, 2975,
2925, 2871, 2849, 1693, 1511, 1384, 1243, 1180, 1141, 1076,
1044, 737, 698, 635. HRMS (ESI) calcd for C H NO S
3
-
1
6
3
7
3
6.7, 128.0, 128.1, 128.5, 136.6, 156.4, 195.8. IR (vmax, cm )
341, 3036, 2959, 2927, 2869, 1693, 1530, 1239, 1134, 1110,
2
7
30
4
+
+
36, 696, 626. HRMS (ESI) calcd for C H NO S [M+H] m/z:
[M+H] m/z: 464.1890; found 464.1883.
16
24
3
10.1471; found 310.1467.
4
.7 General procedure for the synthesis of N-
4
.6.4 (S)-S-3-(Benzyloxycarbonylamino)-5-methylhexyl
benzyloxycarbonyl 3-substituted homotaurines 6
ethanethioate (5d)
Pale yellow solid, mp: 60-61 C, 0.97 g, yield 60%, [α] = +1.4
o
20
D
3
0% H O (1 mL) was dissolved in 98% formic acid (5 mL)
2 2
o o
1
at 0 C and the mixture was stirred at 0 C for 1 h to afford
peroxyformic acid. Thioacetate 5 (1 mmol) was dissolved in
9
(c 1.0, CHCl ). H NMR (400 MHz, CDCl ) δ: 0.90 (d, J = 6.0
3
3
Hz, 3H, CH ), 0.91 (d, J = 6.0 Hz, 3H, CH ), 1.24-1.36 (m, 2H,
CH ), 1.59-1.67 (m, 2H, CH ), 1.71-1.82 (m, 1H, CH), 2.31 (s,
3
3
8% formic acid (2 mL), and then the solution was added
2
2
dropwise to the peroxyformic acid solution in an ice-water bath.
The resulting solution was stirred overnight at room temperature.
After removal of the solvent, the residue was purified by column
chromatography on silica gel (PE/EA: 5/1, v/v) to afford pure N-
benzyloxycarbonyl 3-substituted homotaurine 6.
3
H, CH ), 2.82 (ddd, J = 14.0, 8.8, 7.2 Hz, 1H in CH S), 2.96
3
2
(ddd, J = 14.0, 9.2, 5.6 Hz, 1H in CH S), 3.71-3.85 (m, 1H,
2
CHN), 4.54 (d, J = 9.2 Hz, NH), 5.09 (s, 2H, CH O), 7.30-7.41
2
13
(m, 5H, ArH). C NMR (100 MHz, CDCl ) δ: 22.1, 23.0, 24.8,
3
2
1
1
5.7, 30.6, 35.9, 44.7, 49.0, 66.6, 128.01, 128.0, 128.5, 136.6,
-1
56.0, 195.9. IR (vmax, cm ) 3337, 3031, 2954, 2926, 2868, 1693,
4
.7.1 (S)-3-Benzyloxycarbonylamino-4-phenylbutane-1-sulfonic
acid (6a)
White solid, mp: 69-71 C, 341 mg, yield 94%, [α] = -9.1 (c
530, 1257, 1232, 1111, 1041, 730, 695, 630. HRMS (ESI) calcd
+
for C H NO S [M+H] m/z: 324.1628; found 324.1624.
o
20
D
17
26
3
1
1
6
.0, CHCl ). H NMR (400 MHz, D O) δ: 2.13 (dddd, J = 14.4,
3
2
4
.6.5
(3R,4S)-S-3-(Benzyloxycarbonylamino)-4-methylhexyl
.4, 4.4, 2.8 Hz, 1H in CH ), 2.35 (ddt J = 14.4, 11.2, 7.6 Hz, 1H
2
ethanethioate (5e)
Pale yellow solid, mp: 42-43 C, 0.92 g, yield 57%, [α]
+
in CH ), 2.79 (dd, J = 13.6, 9.6 Hz, 1H in CH ), 3.15-3.25 (m,
o
20
D
2
2
=
2
1
H, CH S), 3.28 (dd, J = 13.6, 4.0 Hz, 1H in CH ), 4.32-4.41 (m,
1
2
2
18.0 (c 1.0, CHCl ). H NMR (400 MHz, CDCl ) δ: 0.86 (d, J =
3
3
H, CHN), 5.32 (d, J = 12.8 Hz, 1H in CH O), 5.34 (d, J = 12.8
2
6
1
1
2
1
1
7
1
1
1
.8 Hz, 3H, CH ), 0.90 (t, J = 7.2 Hz, 3H, CH ), 1.08 (ddq, J =
13
3
3
Hz, 1H in CH O), 7.15-7.48 (m, 10H, ArH). C NMR (100 MHz,
2
3.2, 7.6, 7.2 Hz, 1H in CH ), 1.37-1.42 (m, 1H in CH ), 1.48-
2
2
CDCl ) δ: 22.2, 38.9, 47.4, 57.9, 68.7, 127.2, 127.9, 128.4, 128.6,
3
.60 (m, 2H, CH ), 1.71-1.82 (m, 1H, CH), 2.31 (s, 3H, CH ),
-1
2
3
1
2
28.8, 129.4, 135.0, 136.0, 150.9. IR (vmax, cm ) 3368, 3029,
.76 (ddd, J = 14.0, 8.8, 7.6 Hz, 1H in CH S), 3.00 (ddd, J =
2
953, 2869, 1725, 1497, 1455, 1307, 1151, 1065, 746, 699.
4.0, 9.2, 4.8 Hz, 1H in CH S), 3.65 (ddd, J = 14.0, 9.6, 4.4 Hz,
+
2
HRMS (ESI) calcd for C H NO S [M+H] m/z: 364.1213;
18
22
5
H, CHN), 4.68 (d, J = 9.2 Hz, 1H, NH), 5.10 (s, 2H, CH O),
2
found 364.1207.
13
.28-7.42 (m, 5H, ArH). C NMR (100 MHz, CDCl ) δ: 11.7,
3
4.9, 25.2, 26.2, 30.6, 31.7, 38.9, 54.8, 66.6, 128.0, 128.5, 136.6,
-
1
4.7.2 (S)-3-Benzyloxycarbonylaminobutane-1-sulfonic acid (6b)
56.3, 195.9. IR (vmax, cm ) 3337, 3033, 2962, 2929, 2860, 1691,
20
D
Coloress liquid, 184 mg, yield 64%, [α] = +9.1 (c 1.0, CHCl3).
528, 1240, 1130, 1047, 733, 694, 624. HRMS (ESI) calcd for
1
+
H NMR (400 MHz, CDCl ) δ: 1.40 (d, J = 6.4 Hz, 3H, CH ),
3
3
C H NO S [M+H] m/z: 324.1628; found 324.1634.
17
26
3
2
.01 (dddd, J = 13.6, 7.2, 6.8, 3.6 Hz, 1H in CH ), 2.55 (dddd, J
2
=
13.6, 10.4, 6.4, 4.8 Hz, 1H in CH ), 3.28 (ddd, J = 13.2, 7.2,
2
4
(
.6.6 (S)-S-3,7-Di(benzyloxycarbonylamino)heptyl ethanethioate
5f)
Scale: 2 mmol, pale yellow solid, mp: 103-105 C, 0.83 g, yield
4
.8 Hz, 1H in CH S), 3.39 (ddd, J = 13.2, 10.4, 6.8 Hz, 1H in
2
o
CH S), 4.28 (ddq, J = 6.4, 3.6, 6.4 Hz, 1H, CHN), 5.27 (d, J =
12.4 Hz, 1H in CH O), 5.32 (d, J = 12.4 Hz, 1H in CH O), 7.27-
2
20
1
2
2
8
1
1
2
8%, [α]D = +3.7 (c 1.0, CHCl ). H NMR (400 MHz, CDCl ) δ:
3
3
13
7
4
3
1
2
.60 (m, 5H, ArH). C NMR (100 MHz, CDCl ) δ: 19.7, 25.6,
7.4, 53.3, 68.4, 127.7, 128.2, 128.5, 135.0, 150.7. IR (vmax, cm )
332, 3034, 2977, 2927, 2850, 1727, 1529, 1455, 1301, 1252,
061, 738, 697. HRMS (ESI) calcd for C H NO S [M+H] m/z:
3
.29-1.37 (m, 2H, CH ), 1.38-1.53 (m, 4H, 2CH ), 1.56-1.67 (m,
2
2
-1
H in CH ), 1.67-1.78 (m, 1H in CH ), 2.29 (s, 3H, CH ), 2.73-
2
2
3
.83 (m, 1H in CH S), 2.93 (ddd, J = 13.6, 8.4, 5.6 Hz, 1H in
2
+
12
18
5
CH S), 3.07-3.21 (m, 2H, CH N), 3.58-3.73 (m, 1H, CHN), 4.86
2
2
88.0900; found 288.0889.
(d, J = 8.8 Hz, 1H, NH), 4.98 (br, 1H, NH), 5.05 (d, J = 11.2 Hz,
2
1
3
1
3
1
H in 2CH O), 5.08 (d, J = 11.2 Hz, 2H in CH O), 7.27-7.44 (m,
2
2
13
4
.7.3 (R)-3-Benzyloxycarbonylamino-4-methylpentane-1-
0H, ArH). C NMR (100 MHz, CDCl ) δ: 22.6, 25.6, 29.4,
3
sulfonic acid (6c)
Coloress liquid, 170 mg, yield 54%, [α]
CHCl ). H NMR (400 MHz, CDCl ) δ: 0.93 (d, J = 6.8 Hz, 6H,
2
0.5, 34.6, 35.3, 40.5, 50.4, 66.4, 66.5, 127.91, 127.95, 128.36,
20
D
-
1
= +15.7 (c 1.0,
28.37, 136.4, 136.5, 156.2, 156.4, 195.8. IR (vmax, cm ) 3322,
086, 3067, 3030, 2916, 2850, 1689, 1520, 1454, 1383, 1246,
180, 1141, 1075, 1026. HRMS (ESI) calcd for C H N O S
1
3
3
CH ), 2.13-2.22 (m, 1H in CH ), 2.26-2.40 (m, 2H, CH & 1H in
3
2
25
33
2
5
+
CH ), 3.24 (ddd, J = 13.2, 7.2, 6.0 Hz, 1H in CH S), 3.30-3.37
[
M+H] m/z: 473.2105; found 473.2106.
2
2
(m, 1H in CH S), 4.07 (dt, J = 7.6, 4.8 Hz, 1H, CHN), 5.27 (d, J
2
=
12.4 Hz, 1H in CH O), 5.32 (d, J = 12.4 Hz, 1H in CH O),
2 2
13
4
.6.7
(S)-S-3-(Benzyloxycarbonylamino)-4-[4-
7
.27-7.50 (m, 5H, ArH). C NMR (100 MHz, CDCl ) δ: 16.2,
3
(benzyloxy)phenyl]butyl ethanethioate (5g)
o
18.3, 19.3, 29.7, 48.3, 61.6, 68.5, 127.7, 128.2, 128.4, 135.0,
151.2. IR (vmax, cm ) 3369, 3034, 2964, 2924, 2866, 1725, 1455,
Scale: 4 mmol; white solid, mp: 87-88 C, 1.18 g, yield 64%,
-1
20
1
[
α]D = +20.7 (c 1.0, CHCl ). H NMR (400 MHz, CDCl ) δ:
3
3