Dom´ınguez et al.
R-D-r ibofu r a n ose (5). Likewise, 5 (0.135 g, 0.29 mmol), K2CO3
(0.06 g, 0.44 mmol), and CH3I (0.04 mL, 0.59 mmol) in acetone
(5 mL) for 22 h gave, after flash chromatography (EtOAc/
petroleum ether, 1:4), 3-amino-5-O-benzyl-3-C-cyano-3-deoxy-
1,2-O-isopropylidene-3-N-phenylmethanesulfonyl-R-D-ribofura-
nose (10) (0.039 g, 28%) and 5-O-benzyl-1,2-O-isopropylidene-
3-spiro-(4′-amino-2′,3′-dihydro-2′-N-methyl-1′,1′-dioxide-5′-
phenyl-isothiazolyl)-R-D-ribofuranose (11) (0.039 g, 28%) as
(C-2), 75.8 (C-4), 73.6 (CH2C6H5), 69.6 (C-3), 66.4 (C-5), 44.7
(NCH2C6H5), 26.5, 25.9 (2 × CH3); MS (ES) 549 [M + 1]+, 571
[M + Na]+, 1119 [2M + Na]+. Anal. Calcd for C30H32N2O6S
(548.65 g/mol): C, 65.68; H, 5.88; N, 5.11; S, 5.84. Found: C,
65.59; H, 5.97; N, 5.02; S, 5.62.
N-Meth yla tion of 3-Am in o-5-O-ben zoyl-3-C-cya n o-3-
d e oxy-3-N -p h e n ylm e t h a n e su lfon yl-1,2-O-isop r op yli-
d en e-r-D-r ibofu r a n ose (5a ). Likewise, 5a (0.30 g, 0.64
mmol), K2CO3 (0.132 g, 0.95 mmol), and CH3I (0.08 mL, 1.28
mmol) refluxing in acetone (10 mL) for 2 h gave, after flash
chromatography (EtOAc/petroleum ether, 1:9), 3-amino-5-O-
benzoyl-3-C-cyano-3-deoxy-1,2-O-isopropylidene-3-N-methyl-
3-N-phenylmethanesulfonyl-R-D-ribofuranose (10a ) (240 mg,
76%) and 11a (21 mg, 7%) as colorless solids. 10a : mp 51-53
colorless solids. 10: mp 46-49 °C; [R]25 +72 (c 0.39, CHCl3);
D
IR (KBr) ν 3436, 1630, 1353, 1153, 1029 cm-1; 1H NMR (CDCl3,
200 MHz) δ 7.36-7.30 (m, 10 H, OCH2C6H5, SO2CH2C6H5),
5.92 (d, J 1,2 ) 3.9 Hz, 1 H, H-1), 5.14 (d, 1 H, H-2), 4.70 (d,
J A,B ) 12.1 Hz, 1 H, H-A, OCH2C6H5), 4.59 (d, 1 H, H-B,
OCH2C6H5), 4.57 (dd, J 4,5a ) 4.4 Hz, J 4,5b ) 5.8 Hz, 1 H, H-4),
4.40 (s, 2 H, SO2CH2C6H5), 3.92 (dd, J 4,5b) 5.8 Hz, J 5a,5b ) 11.0
Hz, 1 H, H-5b), 3.84 (dd, 1 H, H-5a), 2.63 (s, 3 H, NCH3), 1.56
(s, 3 H, CH3), 1.36 (s, 3 H, CH3); 13C NMR (CDCl3, 50 MHz) δ
137.3-127.9 (OCH2C6H5, SO2CH2C6H5), 115.6 (CN), 113.4
[OC(CH3)2], 103.2 (C-1), 84.9 (C-2), 77.3 (C-4), 74.0 (OCH2C6H5),
69.2 (C-5), 66.5 (C-3), 60.0 (SO2CH2C6H5), 36.0 (NCH3), 26.4
(CH3), 26.3 (CH3); MS (ES) 473.2 [M + 1]+, 490.3 [M + NH4]+,
495.1 [M + Na]+, 967.3 [2M + Na]+. Anal. Calcd for
°C; [R]25 +53 (c 0.27, CHCl3); IR (KBr) ν 3435, 1723, 1273,
D
1110 cm-1; 1H NMR (CDCl3, 200 MHz) δ 8.12-7.41 (m, 10 H,
OCOC6H5, SO2CH2C6H5), 5.98 (d, J 1,2 ) 3.8 Hz, 1 H, H-1), 5.19
(d, 1 H, H-2), 4.90 (dd, J 4,5a ) 1.7 Hz, J 5a,5b ) 12.1 Hz, 1 H,
H-5a), 4.67 (dd, J 4,5b ) 7.9 Hz, 1 H, H-4), 4.50 (m, 3 H, H-5b,
SO2CH2C6H5), 2.79 (s, 3 H, NCH3),1.56 (s, 3 H, CH3), 1.38 (s,
3 H, CH3); 13C NMR (CDCl3, 50 MHz) δ 166.3 (CO), 133.5-
128.2 (OCOC6H5, SO2CH2C6H5), 115.3 (CN), 113.6 [OC(CH3)2],
103.4 (C-1), 84.7 (C-2), 76.3 (C-4), 65.8 (C-3), 63.4 (C-5), 60.1
(SO2CH2C6H5), 35.9 (NCH3), 26.4 (CH3), 26.2 (CH3); MS (ES)
504 [M + NH4]+, 509 [M + Na]+, 995 [2M + Na]+. Anal. Calcd
for C24H26N2O7S (486.54 g/mol): C, 59.25; H, 5.39; N, 5.76; S,
6.59. Found: C, 59.11; H, 5.60; N, 5.49; S, 6.35. 11a : mp 200-
202 °C; [R]26D +24 (c 0.34, CHCl3); IR (KBr) ν 3457, 2930, 1711,
C
24H28N2O6S (472.56 g/mol): C, 61.00; H, 5.97; N, 5.93; S, 6.78.
Found: C, 61.23; H, 5.81; N, 5.78; S, 6.99. 11: mp 61-62 °C;
[R]25 +52 (c 0.5, CHCl3); IR (KBr) ν 3459, 3368, 2926, 1650,
D
1377, 1273, 1155, 1057 cm-1 1H NMR (CDCl3, 200 MHz) δ
;
7.43-7.28 (m, 10 H, OCH2C6H5, CH2C6H5), 5.80 (d, J 1,2 ) 3.8
Hz, 1 H, H-1), 4.63 (d, 1 H, H-2), 4.57 (dd, J 4,5a ) 2.9 Hz, J 4,5b
) 5.9 Hz, 1 H, H-4), 4.44 (s, 2 H, CH2C6H5), 4.32 (br s, 2 H,
NH2), 3.73 (dd, J 4,5a ) 2.9 Hz, J 5a,5b ) 11.3 Hz, 1 H, H-5a),
3.59 (dd, J 4,5b ) 5.9 Hz, J 5a,5b ) 11.3 Hz, 1 H, H-5b), 2.94 (s, 3
H, NCH3), 1.54 (s, 3 H, CH3), 1.25 (s, 3 H, CH3); 13C NMR
(CDCl3, 50 MHz) δ 146.5 (C-4′), 137.7-128.2 (OCOC6H5,
CH2C6H5), 126.8 (C-5′), 113.8 [OC(CH3)2], 104.2 (C-1), 85.0
(C-2), 75.4 (C-4), 74.3 (CH2C6H5), 69.6 (C-3), 67.2 (C-5), 27.3
(NCH3), 26.6, 26.3 (2 × CH3); MS (ES) 473 [M + 1]+, 967 [2M
+ Na]+. Anal. Calcd for C24H28N2O6S (472.56 g/mol): C, 61.00;
H, 5.97; N, 5.93; S, 6.78. Found: C, 59.92; H, 6.06; N, 5.98; S,
6.85.
1660, 1272, 1058, 719 cm-1 1H NMR (CDCl3, 200 MHz) δ
;
8.07-7.43 (m, 10 H, OCOC6H5, CH2C6H5), 5.95 (d, J 1,2) 3.8
Hz, 1 H, H-1), 4.88 (dd, J 4,5a ) 3.3 Hz, J 4,5b ) 7.5 Hz, 1 H,
H-4), 4.83 (d, 1 H, H-2), 4.62 (m, 4 H, H-5a, H-5b, NH2), 3.17
(s, 3 H, NCH3), 1.68 (s, 3 H, CH3), 1.39 (s, 3 H, CH3); 13C NMR
(CDCl3, 50 MHz) δ 166.5 (CO), 144.5 (C-4′), 133.3-128.4
(OCOC6H5, CH2C6H5), 126.5 (C-5′), 113.6 [OC(CH3)2], 103.9
(C-1), 84.7 (C-2), 73.7 (C-4), 69.4 (C-3), 61.6 (C-5), 27.1 (NCH3),
26.2, 25.9 (2 × CH3); MS (ES) 487 [M + 1]+, 995 [2M + Na]+.
Anal. Calcd for C24H26N2O7S (486.54 g/mol): C, 59.25; H, 5.39;
N, 5.76; S, 6.59. Found: C, 58.19; H, 5.42; N, 5.58; S, 6.88.
N-Ben zyla tion of 3-Am in o-5-O-ben zyl-3-C-cya n o-3-
deoxy-3-N-ph en ylm eth a n esu lfon yl-1,2-O-isop r op yliden e-
r-D-r ib ofu r a n ose (5). Likewise, 5 (0.105 g, 0.23 mmol),
K2CO3 (50 mg, 0.35 mmol), and C6H5CH2Br (0.06 mL, 0.46
mmol) was refluxed in acetone (7 mL) for 4 h gave, after flash
chromatography (EtOAc/petroleum ether, 1:4), 3-amino-3-N-
benzyl-5-O-benzyl-3-C-cyano-3-deoxy-1,2-O-isopropylidene-3-
N-phenylmethanesulfonyl-R-D-ribofuranose (12) (67 mg, 53%)
and 5-O-benzyl-1,2-O-isopropylidene-3-spiro-(4′-amino-2′-N-
benzyl-2′,3′-dihydro-1′,1′-dioxide-5′-phenyl-isothiazolyl)-R-D-ri-
bofuranose (13) (44 mg, 35%) as colorless solids. 12: mp 45-
N-Ben zyla tion of 3-Am in o-5-O-ben zoyl-3-C-cya n o-3-
deoxy-3-N-p h en ylm eth a n esu lfon yl-1,2-O-isopr op ylid en e-
r-D-r ibofu r a n ose (5a ). Likewise, 5a (0.29 g, 0.61 mmol),
K2CO3 (0.130 g, 0.92 mmol), and C6H5CH2Br (0.15 mL, 1.22
mmol) refluxing in acetone (15 mL) for 6 h gave, after flash
chromatography (EtOAc/petroleum ether, 1:4), 3-amino-3-N-
benzyl-5-O-benzoyl-3-C-cyano-3-deoxy-1,2-O-isopropylidene-3-
N-phenylmethanesulfonyl-R-D-ribofuranose (12a ) (162 mg,
47%) and 5-O-benzoyl-1,2-O-isopropylidene-3-spiro-(4′-amino-
2′-N-benzyl-2′,3′-dihydro-l′,1′-dioxide-5′-phenyl-isothiazolyl)-R-
D-ribofuranose (13a ) (10 mg, 3%) as colorless solids. 12a : mp
46 °C; [R]25 +70 (c 0.4, CHCl3); IR (KBr) ν 3435, 2989, 2935,
63-65 °C; [R]25 +79 (c 0.26, CHCl3); IR (KBr) ν 3436, 2927,
D
D
1630, 1496, 1455, 1355, 1154, 1096, 1026 cm-1 1H NMR
;
1721, 1627, 1272, 1096, 1024 cm-1; 1H NMR (CDCl3, 200 MHz)
δ 8.11-7.28 (m, 15 H, OCOC6H5, SO2CH2C6H5, CH2C6H5), 5.93
(d, J 1,2 ) 3.8 Hz, 1 H, H-1), 5.17 (d, J 1,2 ) 3.8 Hz, 1 H, H-2),
4.82 (m, 2 H, H-4, H-5a), 4.46 (m, 5 H, H-5b, CH2C6H5,
SO2CH2C6H5), 1.33 (s, 3 H, CH3), 1.22 (s, 3 H, CH3); 13C NMR
(CDCl3, 50 MHz) δ 166.3 (CO), 136.0-128.0 (OCOC6H5, SO2-
CH2C6H5, CH2C6H5), 115.9 (CN), 113.8 [OC(CH3)2], 103.2
(C-1), 84.4 (C-2), 77.3 (C-4), 66.9 (C-3), 64.2 (C-5), 60.5
(SO2CH2C6H5), 52.6 (CH2C6H5), 26.5 (CH3), 25.9 (CH3); MS
(ES) 580.3 [M + NH4]+, 585.2 [M + Na]+, 1148.3 [2M + Na]+.
Anal. Calcd for C30H30N2O7S (562.64 g/mol): C, 64.04; H, 5.37;
N, 4.98; S, 5.70. Found: C, 63.95; H, 5.17; N, 4.84; S, 5.98.
(CDCl3, 200 MHz) δ 7.41-7.28 (m, 15 H, OCH2C6H5, SO2-
CH2C6H5, NCH2C6H5), 5.83 (d, J 1,2 ) 3.8 Hz, 1 H, H-1), 5.11
(d, 1 H, H-2), 4.70-4.35 (m, 5 H, H-4, OCH2C6H5, SO2CH2C6H5),
4.21 (s, 2 H, NCH2C6H5), 3.91 (d, 2 H, J ) 4.5 Hz, 2 H-5), 1.27
(s, 3 H, CH3), 1.06 (s, 3 H, CH3); 13C NMR (CDCl3, 50 MHz) δ
137.0-127.9 (OCH2C6H5, SO2CH2C6H5, NCH2C6H5), 116.1
(CN), 113.4 [OC(CH3)2O], 100.8 (C-1), 84.4 (C-2), 76.7 (C-4),
73.8 (OCH2C6H5), 69.9 (C-5), 67.5 (C-3), 59.9 (SO2CH2C6H5),
52.3 (NCH2C6H5), 26.3 (CH3), 25.5 (CH3); EM (ES) 549 [M +
1]+, 571 [M + Na]+. Anal. Calcd for C30H32N2O6S (548.6
g/mol): C, 65.68; H, 5.88; N, 5.11; S, 5.84. Found: C, 65.73;
H, 5.94; N, 5.03; S, 5.71. 13: mp 64-66 °C; [R]25 +91 (c 0.53,
13a : mp 210-212 °C; [R]25 +47 (c 0.38, CHCl3); IR (KBr) ν
D
D
3336, 1722, 1644, 1455, 1376, 1271, 1062 cm-1 1H NMR
;
CHCl3); IR (KBr) ν 3434, 3349, 2991, 1659, 1605, 1274, 1163,
1050 cm-1; 1H NMR (CDCl3, 200 MHz) δ 7.49-7.09 (m, 15 H,
NCH2C6H5, OCH2C6H5, CH2C6H5), 5.80 (d, J 1,2 ) 3.8 Hz, 1 H,
H-1), 4.74 (br s, 3 H, H-2, NCH2C6H5), 4.39 (br s, 3 H, H-4,
NH2), 4.22 (d, J ) 6.9 Hz, 2 H, OCH2C6H5), 3.39 (m, 2 H, 2
H-5), 1.60 (s, 3 H, CH3), 1.30 (s, 3 H, CH3); 13C NMR (CDCl3,
50 MHz) δ 146.5 (C-4′), 137.4-127.8 (NCH2C6H5, OCH2C6H5,
CH2C6H5), 126.5 (C-5′), 113.6 [OC(CH3)2], 103.9 (C-1), 84.8
(CDCl3, 200 MHz) δ 7.92-7.28 (m, 15 H, NCH2C6H5, OCOC6H5,
C6H5), 5.94 (d, J 1,2 ) 3.7 Hz, 1 H, H-1), 4.95 (s, 2 H, CH2C6H5),
4.94 (d, 1 H, H-2), 4.64 (br s, 2 H, NH2), 4.62 (m, 1 H, H-4),
4.41(dd, J 4,5a ) 7.7 Hz, J 5a,5b ) 12.4 Hz, 1 H, H-5a), 4.23 (dd,
J 4,5b ) 1.8 Hz, J 5a,5b ) 12.4 Hz, 1 H, H-5b), 1.77 (s, 3 H, CH3),
1.44 (s, 3 H, CH3); 13C NMR (CDCl3, 50 MHz) δ 166.0 (CO),
144.9 (C-4′), 137.3-128.1 (OCOC6H5, CH2C6H5, C6H5), 126.2
852 J . Org. Chem., Vol. 69, No. 3, 2004