Ϫ1
7
6.57 (CH, C-3), 72.77 (CH, C-12), 67.90 (CH, C-7), 61.61
cm 3399, 1653; δ (300 MHz; CDCl –CD OD) 7.21 (br s, 4H,
H 3 3
(
3
CH , OCOCH ), 39.29 (CH , CH NHCO), 34.66 (CH , C-23),
Ar–H), 4.37 (m, 4H, 2 × CH NH), 3.91 (br s, 2H, 2 × 12β-H),
2
2
2
2
2
2
ϩ
ϩ
2.85 (CH , C-22); m/z (FAB) 1109 (M ϩ Na, 4%), 1087 (M
3.80 (br s, 2H, 2 × 7β-H), 3.21 (m, 2H, 2 × 3β-H), 2.25–
1.10 (48H, steroidal H), 0.98 (br s, 6H, 2 × 21-Me), 0.86 (s, 6H,
2 × 19-Me), 0.66 (s, 6H, 2 × 18-Me); δC (75 MHz; CDCl3–
2
ϩ H, 12), 1069 (3), 966 (3), 615 (8), 436 (13), 397 (9), 380 (12),
55 (5), 337 (12), 279 (12), 253 (19), 225 (22), 119 (53), 105 (70).
3
CD OD) 174.71 (C, C-24), 138.61 (C, Ar–C), 128.51 (CH,
3
Bis(3ꢀ-O-hydroxyacetyldeoxycholyl)ethylenediamine
cyclic
Ar–CH), 126.77 (CH, Ar–CH), 72.82 (CH, C-3), 71.38 (CH,
terephthalate (deoxycholaphane) 7b. Bis-bromoacetyl-deoxy-
cholamide 5b (244 mg, 0.23 mmol) was dissolved in dry
DMF (6 ml) and treated with dicaesium terephthalate (102 mg,
C-12), 68.06 (CH, C-7), 43.01 (CH , CH NHCO), 32.36 (CH ,
2
2
2
ϩ
C-23), 31.46 (CH , C-22); m/z (FAB) 940 (M ϩ Na, 43%), 918
(M ϩ H, 43), 900 (8), 809 (8), 637 (11), 615 (11), 577 (10), 555
2
ϩ
0
.23 mmol). The work-up procedure followed was as described
(10), 525 (8), 501 (9), 473 (9), 436 (13), 355 (8), 337 (25), 289
(20), 271 (25), 253 (32), 225 (31), 199 (12), 176 (17), 119 (35),
105 (77).
for the cholaphane 7a. The residue obtained on concentration
in vacuo was purified by column chromatography [0–4% (v/v)
MeOH in CHCl ] [R 0.59 in 10% (v/v) MeOH in CHCl ] to give
3
f
3
the deoxycholaphane 7b (207 mg, 85%) as a white crystalline
solid; mp 196–199 ЊC (Found: C, 68.86; H, 8.73; N, 2.33%. Calc.
for C H N O ؒH O: C, 69.31; H, 8.63; N, 2.60%); IR ν
N,NЈ-Bisdeoxycholyl-m-xylylenediamine 8b. Succinimido
deoxycholate 3b (2.45 g, 5.02 mmol) was dissolved in dry DMF
(20 ml) and to this was added m-xylylenediamine (341 mg, 2.45
mmol). The mixture was stirred at room temperature under
nitrogen atmosphere for 10 h. The reaction mixture was worked
up as described earlier and the product was purified by column
chromatography [10% (v/v) MeOH in CHCl ] (R 0.52) to give
62
90
Ϫ1
2
12
2
max
(
KBr)/cm 3410, 1735, 1648; δH (300 MHz; CDCl –CD OD)
3
3
8
.17 (br s, 4H, Ar–H), 4.83 (br s, 6H, 2 × COCH O and 2 × 3β-
2
H), 3.98 (br s, 2H, 2 × 12β-H), 3.34 (br s, 4H, 2 × CH NHCO),
2
2
6
.40–1.03 (50H, steroidal H), 0.98 (br s, 6H, 2 × 21-Me), 0.91 (s,
H, 2 × 19-Me), 0.67 (s, 6H, 2 × 18-Me); δ (75 MHz; CDCl –
3
f
compound 8b as a white crystalline solid (1.92 g, 87%); mp 145–
146 ЊC (Found: C, 74.29; H, 10.02; N, 2.73%. Calc. for
C H N O ؒH O: C, 74.46; H, 10.04; N, 3.10%); IR ν (KBr)/
C
3
CD OD) 175.35 (C, C-24), 167.12 (C, OCOAr), 165.19 (C,
3
OCOCH ), 133.37 (C, Ar–C), 129.90 (CH, Ar–CH), 76.05 (CH,
2
56 88
2
6
2
max
Ϫ1
C-3), 72.84 (CH, C-12), 61.66 (CH , OCOCH ), 39.54 (CH ,
cm 3386, 1654; δ (300 MHz; CDCl –CD OD) 7.21 (br s, 4H,
2
2
2
H 3 3
CH NHCO), 31.96 (CH , C-23), 31.57 (CH , C-22); m/z (FAB)
Ar–H), 4.36 (m, 4H, 2 × CH NH), 3.94 (br s, 2H, 2 × 12β-H),
2
2
2
2
ϩ
ϩ
1
9
078 (M ϩ Na, 33%), 1056 (M ϩ H, 52), 1036 (17), 993 (10),
58 (11), 935 (100), 919 (17), 891 (9), 857 (11), 813 (16), 796
3.43 (m, 2H, 2 × 3β-H), 2.60–1.00 (50H, steroidal H), 0.95 (d,
J = 6 Hz, 6H, 2 × 21-Me), 0.89 (s, 6H, 2 × 19-Me), 0.65 (s, 6H,
2 × 18-Me); δC (75 MHz; CDCl –CD OD) 174.64 (C-24),
(
6
(
2
36), 778 (12), 738 (28), 715 (10), 662 (70), 632 (14), 604 (40),
00 (15), 578 (76), 552 (38), 521 (12), 493 (18), 460 (18), 439
12), 413 (32), 382 (60), 357 (16), 339 (40), 289 (80), 279 (22),
55 (40), 207 (50), 119 (64), 107 (95).
3
3
138.67 (C, Ar–C), 128.93 (CH, Ar–CH), 126.80 (CH, Ar–CH),
72.92 (CH, C-3), 71.27 (CH, C-12), 43.21 (CH , CH NHCO),
2
2
32.09 (CH , C-23), 31.47 (CH , C-22), 26.99 (CH , C-7); m/z
2 2 2
ϩ ϩ
(
FAB) 908 (M ϩ Na, 28%), 886 (M ϩ H, 100), 868 (13), 850
3
ꢀ-O-Hydroxyacetylcholyl-3ꢀЈ-O-hydroxyacetyldeoxycholyl-
(9), 813 (33), 599 (7), 575 (4), 557 (10), 529 (8), 509 (15), 491
(12), 475 (25), 438 (12), 420 (15), 402 (5), 384 (17), 357 (7), 339
(22), 289 (10), 271 (10), 255 (40), 225 (18), 199 (11), 105 (82).
ethylenediamine cyclic terephthalate (cholaphane) 7c. Bis-
bromoacetylcholic-deoxycholamide 5c (190 mg, 0.17 mmol)
was dissolved in dry DMF (5 ml) and treated with dicaesium
terephthalate (76 mg, 0.17 mmol) at room temperature for 12 h.
The usual work-up gave compound 7c, which was purified by
column chromatography [0–5% (v/v) MeOH in CHCl ] [R 0.57
N,NЈ-Bis(3ꢀ-O-bromoacetylcholyl)-m-xylylenediamine
9a.
Dicholyl-m-xylylenediamine 8a (800 mg, 0.87 mmol) was
treated with bromoacetyl bromide (351 mg, 1.74 mmol) in the
presence of anhydrous K CO (241 mg, 1.74 mmol) in dry
3
f
in 10% (v/v) MeOH in CHCl ] (165 mg, 87%); mp 215 ЊC
3
2
3
(
decomp.) (Found: C, 64.99; H, 8.59; N, 2.94%. Calc. for
CHCl (20 ml). The procedure was the same as that mentioned
3
C H N O ؒ4H O: C, 65.12; H, 8.63; N, 2.45%); IR ν
for the dimers 5a–c and the crude product was purified by
62
90
2
13
Ϫ1
2
max
(
KBr)/cm 3410, 1735, 1650; δH (300 MHz; CDCl –CD OD)
3 3
column chromatography [0–5% (v/v) MeOH in CHCl ] [R 0.69
3
f
8
2
3
0
.17 (br s, 4H, Ar–H), 4.83 (br s, 4H, 2 × COCH O), 4.60 (m,
H, 2 × 3β-H), 3.97 (br s, 2H, 2 × 12β-H), 3.83 (br s, 1H, 7β-H),
in 10% (v/v) MeOH in CHCl ] to give product 9a as a semi-solid
(718 mg, 71%); IR νmax (KBr)/cm 3325, 1733, 1653; δH (300
2
3
Ϫ1
.36 (br s, 4H, 2 × CH NHCO), 2.25–1.02 (49H, steroidal H),
MHz; CDCl ) 7.18 (br s, 4H, Ar–H), 4.56 (m, 2H, 2 × 3βH),
2
3
.99 (br s, 6H, 2 × 21-Me), 0.91 (br s, 6H, 2 × 19-Me), 0.67
4.30 (m, 4H, 2 × CH NH), 3.90 (br s, 2H, 2 × 12β-H), 3.76
2
(
s, 6H, 2 × 18-Me); δ (75 MHz; CDCl –CD OD) 175.39 (C,
(br s, 2H, 2 × 7β-H), 3.70 (s, 4H, 2 × CH Br), 2.40–1.00
C
3
3
2
C-24), 167.12 (C, OCOAr), 165.19 (C, OCOCH ), 133.36
(48H, steroidal H), 0.89 (br s, 6H, 2 × 21-Me), 0.84 (br s, 6H,
2 × 19-Me), 0.60 (s, 6H, 2 × 18-Me).
2
(
C, Ar–C), 129.89 (CH, Ar–CH), 76.06 (CH, C-3), 72.84 (CH,
C-12), 67.99 (CH, C-7), 61.69 (CH , OCOCH ), 39.60 (CH ,
2
2
2
CH NHCO), 31.93 (CH , C-23), 26.86 (CH, C-7Ј); m/z (FAB)
N,NЈ-Bis(3ꢀ-O-bromoacetyldeoxycholyl)-m-xylylenediamine
9b. This was prepared by taking bis(deoxycholyl)-m-xylylene-
diamine (650 mg, 0.73 mmol), bromoacetyl bromide (295 mg,
1.46 mmol), and anhydrous K CO (202 mg, 1.46 mmol) in dry
2
2
ϩ
1071 (M ϩ H, 20%), 1018 (3), 951 (4), 811 (3), 735 (6), 460 (7),
399 (10), 382 (16), 355 (6), 337 (14), 289 (63), 273 (22), 120 (50),
107 (95).
2
3
CHCl (15 ml) and the crude product obtained after usual
3
N,NЈ-Dicholyl-m-xylylenediamine 8a. Succinimido cholate
a (2.22 g, 4.3 mmol) was dissolved in DMF (10 ml) and to this
work-up was subjected to column chromatography [0–4% (v/v)
MeOH in CHCl ] [R 0.60 in 8% (v/v) MeOH in CHCl ] to give
product 9b as a semi-solid (629 mg, 76%); IR νmax (KBr)/cm
3
3
f
3
Ϫ1
was added m-xylylenediamine (299 mg, 2.15 mmol). The reac-
tion mixture was stirred under nitrogen atmosphere at room
temperature for 10 h. The turbid mixture was then filtered. The
clear filtrate was mixed with ice-cold brine (400 ml). The white
solid that separated was filtered off, washed with cold water,
and dried under vacuum. The dried solid was purified by col-
umn chromatography [10% (v/v) MeOH in CHCl ] (R 0.40) to
3415, 1730, 1652; δH (300 MHz; CDCl ) 7.17 (m, 4H, Ar–H),
3
4.72 (m, 2H, 2 × 3β-H), 4.30 (m, 4H, 2 × CH NH), 3.90 (s, 2H,
2
2 × 12β-H), 3.74 (s, 4H, 2 × CH Br), 2.30–1.03 (50H, steroidal
2
H), 0.91 (d, J = 6 Hz, 6H, 2 × 21-Me), 0.86 (s, 6H, 2 × 19-Me),
0.60 (s, 6H, 2 × 18-Me).
3
f
yield the pure product 8a (1.78 g, 88%) as a white crystalline
solid; mp 153–155 ЊC (Found: C, 71.81; H, 9.80; N, 3.07%. Calc.
for C H N O ؒH O: C, 71.91; H, 9.69; N, 2.99%); ν (KBr)/
Bis(3ꢀ-O-hydroxyacetylcholyl)-m-xylylenediamine
terephthalate 10a. Bis(bromoacetylcholyl)-m-xylylenediamine
9a (300 mg, 0.25 mmol) was dissolved in DMF (8 ml) and to
cyclic
56
88
2
8
2
max
9
22
J. Chem. Soc., Perkin Trans. 1, 2002, 918–923