6546 Journal of Medicinal Chemistry, 2006, Vol. 49, No. 22
Wilkinson et al.
(m, 1H, H4′), 3.98-4.03 (m, 1H, H2′), 5.43 (s, 2H, CH2O), 5.48 (d,
3J1′-2′ ) 8.8 Hz, 1H, H1′), 7.91-8.12 (m, 4H, Ph), 8.37 (s, 1H,
triazole CH); 13C {1H} NMR (100 MHz, 2% D2O in DMSO-d6) δ
58.42 (CH2O), 60.38 (C6′), 68.39 (C4′), 69.24 (C2′), 73.52 (C3′),
78.46 (C5′), 88.19 (C1′), 124.01 (triazole CH), 126.21 (Ph CH),
130.10 (Ph CH), 132.16 (Ph C), 141.69 (Ph C), 148.13 (triazole
C), 164.62 (CdO); HRMS (ESI) calcd for C16H19N4O9S-
443.087 822, found 443.087 859.
Hz, 1H, NHAc CONH), 7.91-8.10 (m, 4H, Ph), 8.27 (s, 1H,
triazole CH); 13C {1H} NMR (100 MHz, DMSO-d6) δ 23.36 (NHAc
CH3), 55.20 (C2′), 58.99 (CH2O), 61.35 (C6′), 70.61 (C4′), 74.57
(C3′), 80.81 (C5′), 86.74 (C1′), 124.34 (triazole CH), 126.76 (Ph
CH), 130.69 (Ph CH), 132.76 (Ph C), 142.10 (Ph C), 148.87
(triazole C), 165.13 (CdO), 169.82 (CdO); HRMS (ESI) calcd
for C18H22N5O9S- 484.114 372, found 484.113 226.
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(2′,3′,4′-tri-O-
acetyl-â-D-glucuronic acid methyl ester)-1H-1,2,3-triazole (3e).
The title compound was prepared according to general procedure
1 and isolated as a white foam (307 mg, 92%): Rf 0.58 (2:8 hexanes:
EtOAc); 1H NMR (400 MHz, DMSO-d6) δ 1.76 (s, 3H, OAc CH3),
1.96 (s, 3H, OAc CH3), 1.99 (s, 3H, OAc CH3), 3.60 (s, 3H,
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(2′,3′,4’-tri-O-
acetyl-â-D-arabinopyranosyl)-1H-1,2,3-triazole (3c). The title
compound was prepared according to general procedure 1 and
isolated as a white foam (228 mg, 0.42 mmol, 88%): Rf 0.55 (2:8
1
hexanes:EtOAc); H NMR (400 MHz, DMSO-d6) δ 1.78 (s, 3H,
3
OAc CH3), 1.93 (s, 3H, OAc CH3), 2.13 (s, 3H, OAc CH3), 4.02
COCH3), 4.79 (d, J5′-4′ ) 10.0 Hz, 1H, H5′), 5.21-5.26 (m, 1H,
2
3
(dd, J5′-5′′ ) 13.2 Hz, J5′-4′ ) 1.6 Hz, 1H, H5′), 4.14-4.18 (m,
1H, H5′), 5.28-5.30 (m, 1H, H4′), 5.38 (dd, 3J3′-2′ ) 10.0 Hz, 3J3′-4′
) 3.6 Hz, 1H, H3′), 5.42 (s, 2H, CH2O), 5.55-5.60 (m, 1H, H2′),
6.13 (d, 3J1′-2′ ) 9.2 Hz, 1H, H1′), 7.53 (br s, 2H, SO2NH2), 7.91-
8.10 (m, 4H, Ph CH), 8.46 (s, 1H, triazole H); 13C {1H} NMR
(100 MHz, DMSO-d6) δ 20.66 (OAc CH3), 21.07 (OAc CH3), 21.40
(OAc CH3), 58.81 (CH2O), 67.18 (C5′), 68.57 (C4′), 68.69 (C2′),
70.95 (C3′), 85.52 (C1′), 125.11 (triazole CH), 126.76 (Ph CH),
130.67 (Ph CH), 132.71 (Ph C), 142.86 (Ph C), 148.91 (triazole
C), 165.11 (CdO), 169.24 (CdO), 170.20 (CdO), 170.55 (Cd
O); HRMS (ESI) calcd for C21H23N4O11S- 539.108 952, found
539.107 401. Anal. (C21H24N4O11S‚1.5H2O) C, H, N, S.
H4′), 5.43 (s, 2H, CH2O), 5.57-5.62 (m, 1H, H3′), 5.73-5.78 (m,
3
1H, H2′), 6.40 (d, J1′-2′ ) 9.2 Hz, 1H, H1′), 7.54 (br s, 2H, SO2-
NH2), 7.91-8.12 (m, 4H, Ph H), 8.65 (s, 1H, triazole H); 13C {1H}
NMR (100 MHz, DMSO-d6) δ 20.56 (OAc CH3), 20.90 (OAc CH3),
20.95 (OAc CH3), 53.30 (COCH3), 58.90 (CH2O), 69.05 (C4′), 70.48
(C3′), 72.13 (C2′), 73.56 (C5′), 84.48 (C1′), 124.90 (triazole CH),
126.77 (Ph CH), 130.69 (Ph CH), 132.67 (Ph C), 143.28 (triazole
C or Ph C), 148.92 (triazole C or Ph C), 165.09 (CdO), 167.24
(CdO), 169.10 (CdO), 169.98 (CdO), 170.19 (CdO); HRMS
(ESI) calcd for C23H25N4O13SCl- 633.091 109, found 0.633.094 227.
Anal. (C23H26N4O13S‚1.5H2O) C, H, N, S.
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(â-D-glucuron-
ic acid methyl ester)-1H-1,2,3-triazole (3e′). The title compound
was prepared according to general procedure 1 and isolated as a
hygroscopic white foam (42 mg, 0.08 mmol, 72%): Rf 0.32 (1:9
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(â-D-arabinopy-
ranosyl)-1H-1,2,3-triazole (3c′). The title compound was prepared
according to procedure 1 and isolated as a white solid (105 mg,
1
0.25 mmol, 84%): Rf 0.26 (3:7 EtOH:CHCl3); mp 184-189 °C;
CH3OH:EtOAc); H NMR (400 MHz, 2% D2O in DMSO-d6) δ
3
1H NMR (400 MHz, 2% D2O in DMSO-d6) δ 3.53 (dd, J3′-2′
)
3.27-3.32 (m, 1H, H3), 3.96-3.01 (m, 1H, H4′), 3.65 (s, 3H,
3
3
9.6 Hz, J3′-4′ ) 3.6 Hz, 1H, H3′), 3.72-3.74 (m, 2H, H4′, H5′),
COCH3), 3.84-3.88 (m, 1H, H2′), 4.63 (d, J5′-4′ ) 9.6 Hz, 1H,
3.78 (dd, 2J5′′-5′ ) 12.4 Hz, 3J5′′-4′ ) 2.0 Hz, 1H, H5′′), 3.98-4.03
H5′), 5.42 (s, 2H, CH2O), 5.72 (d, 3J1′-2′ ) 9.6 Hz, 1H, H1′), 7.91-
8.12 (m, 4H, Ph H), 8.46 (s, 1H, triazole CH); 13C {1H} NMR
(100 MHz, 2% D2O in DMSO-d6) δ 52.81 (COCH3), 58.92 (CH2O),
71.56 (C3′), 71.89 (C4′), 76.68 (C2′), 78.00 (C5′), 87.79 (C1′), 125.09
(triazole CH), 126.80 (Ph CH), 130.73 (Ph CH), 136.85 (Ph C),
142.40 (triazole C or Ph C), 148.49 (triazole C or Ph C), 165.20
(CdO), 169.35 (CdO); HRMS (ESI) calcd for C17H19N4O10S-
471.082 737, found 471.082 075.
3
(m, 1H, H2′), 5.41 (d, J1′-2′ ) 10.0 Hz, 1H, H1′), 5.43 (s, 2H,
CH2O), 8.36 (s, 1H, triazole CH), 7.91-8.12 (m, 4H, Ph); 13C {1H}
NMR (100 MHz, 2% D2O in DMSO-d6) δ 59.06 (CH2O), 69.03
(C4′), 69.96 (C5′, C2′), 73.86 (C3′), 89.10 (C1′), 124.59 (triazole CH),
126.79 (Ph CH), 130.70 (Ph CH), 132.74 (Ph C), 142.25 (triazole
C or Ph C), 148.81 (triazole C or Ph C), 165.21 (CdO); HRMS
(ESI) calcd for C15H17N4O8S- 413.077 258, found 413.076 552.
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(2′-acetamido-
2′-deoxy-3′,4′,6′-tri-O-acetyl-â-D-glucopyranosyl)-1H-1,2,3-tria-
zole (3d). The title compound was prepared according to the general
procedure 1 and isolated as a white solid (292 mg, 0.60 mmol,
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(hepta-O-acetyl-
â-D-maltosyl)-1H-1,2,3-triazole (3f). The title compound was
prepared according to general procedure 1 and isolated as a white
foam (185 mg, 0.21 mmol, 91%): Rf 0.46 (2:8 hexanes:EtOAc);
1H NMR (400 MHz, DMSO-d6) δ 1.71 (s, 3H, OAc CH3), 1.93 (s,
6H, 2×OAc CH3), 1.96 (s, 3H, OAc CH3), 1.97 (s, 3H, OAc CH3),
1.99 (s, 3H, OAc CH3), 2.02 (s, 3H, OAc CH3), 3.97-4.02 (m,
2H, GlcR H5′, Glcâ H6′), 4.07-4.17 (m, 3H, GlcR H6′′, Glcâ H4′,
1
89%): Rf 0.45 (100% EtOAc); mp 217-218 °C; H NMR (400
MHz, DMSO-d6) δ 1.55 (s, 3H, NHAc CH3), 1.92 (s, 3H, OAc
CH3), 1.97 (s, 3H, OAc CH3), 1.98 (s, OAc CH3), 4.03 (dd, 2J6′-6′′
) 12.4 Hz, 3J6′-5′ ) 2.0 Hz, 1H, H6′), 4.12 (dd, 2J6′′-5′ ) 12.8 Hz,
3
3
3J6′′-5′ ) 5.6 Hz, 1H, H6′), 4.23 (ddd, J5′-4′ ) 10.0 Hz, J5′-6′′
)
Glcâ H6′), 4.32 (ddd, 3J5′-4′ ) 10.0 Hz, 3J5′-6′ ) 5.6 Hz, 3J5′-6′′
2.4 Hz, 1H, Glcâ H5′), 4.42 (dd, 2J6′′-6′ ) 12.4 Hz, 3J6′′-5′ ) 2 Hz,
)
5.6 Hz, 3J5′-6′ ) 2.0 Hz, 1H, H5′), 4.56-4.64 (m, 1H, H2′), 5.06-
5.10 (m, 1H, H4′), 5.30-5.35 (m, 1H, H3′), 5.38-5.45 (m, 2H,
CH2O), 6.11 (d, J1′-2′ ) 9.6 Hz, 1H, H1′), 7.54 (s, 2H, SO2NH2),
7.91-8.12 (m, 4H, Ph H), 8.05 (d, JNH-2 ) 9.6 Hz, 1H, NHAc
3
3
1H, Glcâ H6′′), 4.89 (dd, 1H, J2′-3′ ) 10.4 Hz, J2′-1′ ) 3.6 Hz,
1H, GlcR H2′), 4.96-5.01 (m, 1H, GlcR H4′), 5.19-5.24 (m, 1H,
GlcR H3′), 5.33 (d, 3J1′-2′ ) 4.0 Hz, 1H, GlcR H1′), 5.38-5.45 (m,
2H, CH2O), 5.49-5.53 (m, 1H, Glcâ H2′), 5.55-5.60 (m, 1H, Glcâ
3
3
CONH), 8.44 (s, triazole H); 13C {1H} NMR (100 MHz, DMSO-
d6) δ 20.96 (OAc CH3), 21.10 (OAc CH3), 21.20 (OAc CH3), 22.97
(NHAc CH3), 52.74 (C2′), 58.96 (CH2O), 62.45 (C6′), 68.66 (C3′),
72.99 (C4′), 74.10 (C5′), 85.45 (C1′), 124.49 (triazole CH), 126.75
(Ph CH), 130.70 (Ph CH), 132.71 (Ph CH), 142.64 (Ph C), 148.91
(triazole C), 165.10 (CdO), 170.02 (CdO), 170.10 (CdO), 170.27
(CdO), 170.71 (CdO); HRMS (ESI) calcd for C24H28N5O12S-
610.146 066, found 610.145 354. Anal. (C24H29N5O12S‚0.5H2O) C,
H, N, S.
3
H3′), 6.31 (d, J1′-2′ ) 8.8 Hz, 1H, Glcâ H1′), 7.54 (s, 2H, SO2-
NH2), 7.91-8.10 (m, 4H, Ph CH), 8.47 (s, 1H, triazole H); 13C
{1H} NMR (100 MHz, DMSO-d6) δ 20.57 (OAc CH3), 20.95 (OAc
CH3), 21.01 (OAc CH3), 21.02 (OAc CH3), 21.12 (OAc CH3), 21.19
(OAc CH3), 21.25 (OAc CH3), 58.91 (CH2O), 62.06 (GlcR C6′),
63.45 (Glcâ C6′), 68.37 (GlcR C4′), 68.85 (Glcâ C4′), 69.58 (GlcR
C3′), 70.11 (GlcR C2′), 71.38 (Glcâ C3′), 73.94 (GlcR C5′), 74.58
(Glcâ C5′), 74.96 (Glcâ C5′), 79.85 (Glcâ C2′), 84.16 (Glcâ C1′),
96.41 (GlcR C1′), 124.74 (triazole CH), 126.76 (Ph CH), 130.67
(Ph CH), 132.68 (Ph C), 143.06 (Ph C), 148.91 (triazole C), 165.09
(CdO), 169.36 (CdO), 169.84 (CdO), 170.19 (CdO), 170.35 (Cd
O), 170.53 (CdO), 170.67 (CdO), 170.78 (CdO); HRMS (ESI)
calcd for C36H43N4O21S- 899.214 599, found 899.211 425. Anal.
(C36H44N4O21S‚1.5H2O) C, H, N, S.
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(2′-acetamido-
2′-deoxy-â-D-glucopyranosyl)-1H-1,2,3-triazole (3d′). The title
compound was prepared according to the general procedure 1 and
isolated as an off-white solid (180 mg, 0.38 mmol, 68%) Rf 0.09
1
(3:7 EtOH:CHCl3); mp 205-208 °C (dec); H NMR (400 MHz,
2% D2O in DMSO-d6) δ 1.57 (s, 3H, NHAc CH3), 3.22-3.27 (m,
1H, H4′), 3.68-3.46 (m, 2H, H5′, H6′), 3.49-3.54 (m, 1H, H3′),
3.65-3.69 (m, 1H, H6′′), 4.01-4.08 (m, 1H, H2′), 5.39 (s, 2H,
4-({[4-(Aminosulfonyl)benzoyl]oxy}methyl-1-(â-D-maltosyl)-
1H-1,2,3-triazole (3f′). The title compound was prepared according
to general procedure 1 and isolated as a white foam (161 mg, 0.26
3
3
CH2O), 5.71 (d, J1′-2′ ) 9.6 Hz, 1H, H1′), 7.85 (d, JNH-2 ) 9.2