J. Ombouma et al. / Bioorg. Med. Chem. 22 (2014) 6353–6359
6357
5.3.2.3. Compound 3c. We introduced 0.200 g of 2c and we
obtained 0.431 g (yield : 88%) and 0.441 g (MW: 90%). HRMS
23H31N2O6SSi [M+H]+: 491.1672, found 491.1675
(d, J = 9.2 Hz, 1H, NHCH), 7.74–7.68 (m, 4H, 4Â CHortho), 7.50–7.44
(m, 2H, 2Â CHpara), 7.44–7.37 (m, 4H, 4Â CHmeta), 5.84–5.80 (m, 2H,
H-2, H-3), 5.34 (br s, 1H, H-1), 4.90–4.88 (m, 1H, H-4), 3.92 (d,
J = 6.2 Hz, 1H, H-5), 2.07 (s, 3H, CH3), 1.08 (s, 9H, 3Â CH3), 1.07
(s, 3H, CH3COO). 13C NMR (101 MHz, DMSO-d6) d 170.0 (C@O),
135.6 (CHortho), 132.1 (CSi), 130.3 (C-2), 129.9 (CHpara), 128.9 (C-
3), 127.5 (CHmeta), 78.8 (C-1), 71.7 (C-5), 69.4 (C-4), 26.8
(C(CH3)3), 20.8 (CH3COO), 19.1 (C(CH3)3), 18.3 (CH3).
D
calcd for
(0.3 mDa).
C
5.3.2.3.1. N-[1-(4-O-Acetyl-5-anhydro-2,3-dideoxy-
pent-2-enopyranosyl)]-N-(O-tert-butyldiphenylsilyl)sulfamide
anomer
, 60%). 1H NMR (400 MHz, DMSO-d6) d 9.13 (s, 1H,
a
-D-erythro-
(3c,
a
NHOSi), 8.86 (d, J = 9.0 Hz, 1H, NHCH), 7.74–7.67 (m, 4H, 4Â
CHortho), 7.50–7.44 (m, 2H, 2Â CHpara), 7.44–7.37 (m, 4H, 4Â
CHmeta), 6.04 (tdd, J = 9.9, 4.9, 1.3 Hz, 1H, H-3), 5.99–5.96 (m, 1H,
H-2), 5.35–5.31 (m, 1H, H-1), 4.90–4.84 (m, 1H, H-4), 4.18 (dd,
J = 13.1, 1.3 Hz, 1H, H-5a), 3.74 (dd, J = 13.1, 1.3 Hz, 1H, H-5b),
2.03 (s, 3H, CH3COO), 1.07 (s, 9H, 3Â CH3). 13C NMR (101 MHz,
DMSO-d6) d 170.2 (C@O), 135.9 (CHortho), 132.3 (CSi), 130.9 (C-2),
130.2 (CHpara), 127.79 (CHmeta), 125.1 (C-3), 75.5 (C-1), 63.2 (C-4),
61.8 (C-5), 26.95 (C(CH3)3), 21.04 (CH3COO), 19.3 (C(CH3)3).
5.3.2.5.2.
N-[1-(4-O-Acetyl-6-anhydro-2,3-dideoxy-b-L-erythro-
hex-2-enopyranosyl)]-N-(O-tert-butyldiphenylsilyl)sulfamide (3e, ano-
mer b, 16%). 1H NMR (400 MHz, DMSO-d6) d 9.10 (s, 1H, NHOSi),
8.97 (d, J = 8.9 Hz, 1H, NHCH), 7.74–7.68 (m, 4H, 4Â CHortho), 7.50–
7.44 (m, 2H, 2Â CHpara), 7.44–7.37 (m, 4H, 4Â CHmeta), 5.90–5.85
(m, 2H, H-2, H-3), 5.32 (br s, 1H, H-1), 4.88–4.85 (m, 1H, H-4),
3.94 (d, J = 6.2 Hz, 1H, H-5), 2.07 (s, 3H, CH3), 1.08 (s, 9H, 3Â CH3),
1.07 (s, 3H, CH3COO). 13C NMR (101 MHz, DMSO-d6) d 170.0
(C@O), 135.6 (CHortho), 132.1 (CSi), 130.3 (C-2), 129.9 (CHpara),
128.9 (C-3), 127.5 (CHmeta), 76.2 (C-1), 69.6 (C-4), 65.0 (C-5), 26.8
(C(CH3)3), 20.8 (CH3COO), 19.1 (C(CH3)3), 18.3 (CH3).
5.3.2.3.2. N-[1-(4-O-Acetyl-5-anhydro-2,3-dideoxy-b-D-threo-pent-
2-enopyranosyl)]-N-(O-tert-butyldiphenylsilyl)sulfamide (3c, anomer
b, 40%). 1H NMR (400 MHz, DMSO-d6) d 9.15 (s, 1H, NHOSi), 8.96
(d, J = 9.0 Hz, 1H, NHCH), 7.74–7.67 (m, 4H, 4Â CHortho), 7.50–7.44
(m, 2H, 2Â CHpara), 7.44–7.37 (m, 4H, 4Â CHmeta), 6.01–5.99 (m,
1H, H-3), 5.88 (ddd, J = 10.1, 2.2, 1.3 Hz, 1H, H-2), 5.26 (dd, J = 9.0,
2.0 Hz, 1H, H-1), 5.10–5.04 (m, 1H, H-4), 3.81 (dd, J = 11.8, 4.9 Hz,
1H, H-5a), 3.80 (dd, J = 11.8, 5.8 Hz, 1H, H-5b), 2.03 (s, 3H, CH3COO),
1.07 (s, 9H, 3Â CH3). 13C NMR (101 MHz, DMSO-d6) d 170.3 (C@O),
135.9 (CHortho) 132.3 (CSi), 130.6 (C-2), 130.2 (CHpara), 127.8 (C-3),
127.8 (CHmeta), 77.2 (C-1), 64.1 (C-4), 62.2 (C-5), 26.98 (C(CH3)3),
21.0 (CH3COO), 19.3 (C(CH3)3).
5.3.3. General procedure for the synthesis of compound 4
To a solution of compound 3 (0.63 mmol) in 7 ml of CH3CN was
added 1.7 equiv of HFÁpyr complex (70%) at room temperature for
3 h. The reaction was then quenched by addition of Et3N (5 ml) and
the mixture was concentrated under vacuum. The crude product
was then purified by silica gel column chromatography using
diethyl ether and pentane as eluent (4a, 4b and 4e: Et2O/pentane
7:3; 4c and 4d Et2O/pentane 8:2). The expected compound 4 (mix-
ture
a/b) are obtained in 85% yield.
5.3.2.4. Compound 3d.
We introduced 0.200 g of 2d and we
obtained 0.421 g (yield
D
: 86%) and 0.441 g (MW: 90%). HRMS
5.3.3.1. Compound 4a. We introduced 0.353 g of 3a and we
+
calcd for
(0.0 mDa).
C23H31N2O6SSi [M+H]
:
491.1672, found 491.1672
obtained 0.173 g (yield: 85%). HRMS calcd for C10H17N2O8S
[M+H]+: 325.0706, found 325.0703 (À0.3 mDa).
5.3.2.4.1. N-[1-(4-O-Acetyl-5-anhydro-2,3-dideoxy-
pent-2-enopyranosyl)]-N-(O-tert-butyldiphenylsilyl)sulfamide
anomer
, 60%). 1H NMR (400 MHz, DMSO-d6) d 9.13 (s, 1H,
a
-L
-erythro-
5.3.3.1.1. N-[1-(4,6-Di-O-acetyl-2,3-dideoxy-
a-D
-erythro-hex-2-
77%). 1H
(3d,
eno-pyranosyl)]-N-hydroxysulfamide (4a, anomer
a,
a
NMR (400 MHz, DMSO-d6) d 6.92 (s, 1H, NHOH), 6.69 (s, 1H,
NHCH), 5.87 (td, J = 10.5, 1.8 Hz, 1H, H-3), 5.79 (ddd, J = 10.5, 3.2,
2.5 Hz, 1H, H-2), 5.24 (ddd, J = 9.2, 2.9, 1.8 Hz, 1H, H-1), 5.12–
5.10 (m, 1H, H-4), 4.12 (dd, J = 12.0, 4.1 Hz, 1H, H-6a), 4.12–4.08
(m, 1H, NHOH), 4.08–4.05 (m, 1H, H-5), 4.03 (dd, J = 11.6, 4.3 Hz,
1H, H-6b), 2.05 (s, 3H, CH3COO), 2.02 (s, 3H, CH3COO). 13C NMR
(101 MHz, DMSO-d6) d 170.0 (C@O), 169.8 (C@O), 130.4 (s, 1H, C-
3), 127.0 (C-2), 87.5 (C-1), 65.8 (C-5), 64.8 (C-4), 62.8 (C-6), 20.4
(CH3COO).
NHOSi), 8.86 (d, J = 9.0 Hz, 1H, NHCH), 7.75–7.67 (m, 4H, 4Â
CHortho), 7.50–7.44 (m, 2H, 2Â CHpara), 7.44–7.38 (m, 4H, 4Â
CHmeta), 6.04 (tdd, J = 10.1, 4.9, 1.4 Hz, 1H, H-3), 6.02–5.99 (m,
1H, H-2), 5.33 (dd, J = 9.0, 1.8 Hz, 1H, H-1), 4.89–4.84 (m, 1H, H-
4), 4.18 (dd, J = 13.2, 2.9 Hz, 1H, H-5a), 3.74 (dd, J = 13.2, 1.4 Hz,
1H, H-5b), 2.03 (s, 3H, CH3COO), 1.07 (s, 9H, 3Â CH3). 13C NMR
(101 MHz, DMSO-d6) d 170.3 (C@O), 135.87 (CHortho), 132.26
(CSi), 130.9 (C-2), 130.2 (CHpara), 127.80 (CHmeta), 125.1 (C-3),
75.5 (C-1), 63.2 (C-4), 61.8 (C-5), 26.96 (C(CH3)3), 21.05 (CH3COO),
19.30 (C(CH3)3).
5.3.3.1.2. N-[1-(4,6-Di-O-acetyl-2,3-dideoxy-b-D-threo-hex-2-eno-
pyranosyl)]-N-hydroxysulfamide (4a, anomer b, 23%). 1H NMR
(400 MHz, DMSO-d6): d 6.90 (s, 1H, NHOH), 6.68 (s, 1H, NHCH),
5.84 (td, J = 10.5, 1.6 Hz, 1H, H-3), 5.79 (td, J = 10.5, 1.3 Hz, 1H,
H-2), 5.33–5.28 (m, 1H, H-1), 5.14–5.12 (m, 1H, H-4), 4.12–4.08
(m, 3H, NHOH, H-6a, H-6b), 3.89 (ddd, J = 8.2, 4.7, 3.2 Hz, 1H,
H-5), 2.04 (s, 3H, CH3COO), 2.03 (s, 3H, CH3COO). 13C NMR
(101 MHz, DMSO-d6) d 170.0 (C@O), 169.8 (C@O), 132.9 (C-3),
126.0 (C-2), 90.3 (C-1), 72.1 (C-5), 64.3 (C-4), 62.9 (C-6), 20.6
(CH3COO).
5.3.2.4.2. N-[1-(4-O-Acetyl-5-anhydro-2,3-dideoxy-b-L-thréo-pent-
2-enopyranosyl)]-N-(O-tert-butyldiphenylsilyl)sulfamide (3d, anomer
b, 40%). 1H NMR (400 MHz, DMSO-d6) d 9.15 (s, 1H, NHOSi), 8.95
(d, J = 9.0 Hz, 1H, NHCH), 7.75–7.67 ((m, 4H, 4Â CHortho), 7.50–7.44
(m, 2H, 2Â CHpara), 7.44–7.38 (m, 4H, 4Â CHmeta), 5.99–5.97 (m,
1H, H-3), 5.90 (ddd, J = 10.1, 2.1, 1.3 Hz, 1H, H-2), 5.26 (dd, J = 9.0,
1.9 Hz, 1H, H-1), 5.12–5.03 (m, 1H, H-4), 3.82 (dd, J = 11.7, 6.0 Hz,
1H, H-5a), 3.79 (dd, J = 11.7, 4.7 Hz, 1H, H-5b), 2.03 (s, 2H), 2.03 (s,
3H, CH3COO), 1.08 (s, 9H, 3Â CH3). 13C NMR (101 MHz, DMSO-d6)
d 170.2 (C@O), 135.85 (CHortho), 132.3 (CSi), 130.6 (C-2), 130.1
(CHpara), 127.82 (C-3), 127.80 (CHmeta), 77.2 (C-1), 64.1 (C-4), 62.2
(C-5), 26.98 (C(CH3)3), 21.00 (CH3COO), 19.30 (C(CH3)3).
5.3.3.2. Compound 4b. We introduced 0.357 g of 3b and we
obtained 0.175 g (yield: 85%). HRMS calcd for
C10H17N2O8S
[M+H]+: 325.0706, found 325.0703 (À0.3 mDa).
5.3.3.2.1. N-[1-(4,6-Di-O-acetyl-2,3-dideoxy-
a
-
D
-threo-hex-2-eno-
5.3.2.5. Compound 3e. We introduced 0.214 g of 2e and we
pyranosyl)]-N-hydroxysulfamide (4b, anomer a
, 77%). 1H NMR
obtained 0.444 g (yield
calcd for
24H33N2O6SSi [M+H]+: 505.1829 found 505.1826
(À0.3 mDa).
5.3.2.5.1. N-[1-(4-O-Acetyl-6-anhydro-2,3-dideoxy-
2-enopyranosyl)]-N-(O-tert-butyldiphenylsilyl)sulfamide (3e, anomer
, 84%). 1H NMR (400 MHz, DMSO-d6) d 9.16 (s, 1H, NHOSi), 8.78
D
: 88%) and 0.454 g (MW: 90%). HRMS
(400 MHz, DMSO-d6) d 6.92 (s, 1H, NHOH), 6.69 (s, 1H, NHCH),
6.07 (ddd, J = 9.9, 5.3, 1.4 Hz, 1H, H-3), 6.02 (dd, J = 9.9, 3.3 Hz,
1H, H-2), 5.42–5.38 (m, 1H, H-1), 4.96 (dd, J = 5.2, 2.5 Hz, 1H, H-
4), 4.40 (dd, J = 6.5, 2.5 Hz, 1H, H-5), 4.13–4.10 (m, 1H, NHOH),
4.09 (dd, J = 12.0, 4.1 Hz, 1H, H-6a), 4.06 (dd, J = 11.2, 6.5 Hz, 1H,
H-6b), 1.95 (s, 6H, 2Â CH3COO). 13C NMR (101 MHz, DMSO-d6) d
C
a-L-threo-hex-
a