M. I. Attia, M. Timmermann, P. Högger, C. Herdeis
FULL PAPER
ArH), 8.27 (d, J = 8.8 Hz, 2 H, ArH) ppm. 13C NMR ([D6]-
10.38 (2 s, 2 H, NH and OH) ppm. 13C NMR ([D6]DMSO): δ =
DMSO): δ = 24.6 (CH3), 25.8 (CH3), 36.1 (C-2Ј), 42.4 (C-6), 50.1 24.6 (CH3), 25.8 (CH3), 34.2 (C-2), 42.6 (C-6Ј), 49.9 (C-4Ј), 63.9
(C-4), 51.3 (OCH3), 63.8 (C-7), 68.7 (-CH2-C6H4), 72.6, 73.3 (C- (C-7Ј), 69.8 (-CH2-C6H5), 72.9, 73.3 (C-3Јa, C-7Јa), 108.0 (C-2Ј)
3a, C-7a), 108.4 (C-2) 115.5, 128.7, 129.9, 131.4 (ArCH), 121.3, 115.3, 127.9, 128.1, 128.5, 129.3 (ArCH), 130.7, 136.2, 161.7 (ArC),
130.0, 135.7, 161.7 (ArC), 174.4 (O=C) ppm. C24H28N2O10
(536.55): calcd. C 53.72, H 5.26, N 5.22; found C 53.38, H 4.89, N
5.12.
S
166.5 (O=C) ppm. ESI MS: m/z = 493.4 [M + 1]+. C23H28N2O8S
(492.54): calcd. C 56.09, H 5.73, N 5.69; found C 55.84, H 5.33, N
5.36.
Methyl (3aS,4R,7R,7aR)-5-[4-(3-Chlorobenzyloxy)phenylsulfonyl]-
hexahydro-7-hydroxy-2,2-dimethyl-1,3-dioxolo[4,5-c]piperid-4-yl]-
acetate (16e): Following the general procedure 0.39 g (76%) of 16e
was obtained as white solid m.p. 65–67 °C. [α]2D5 = –16.0 (c = 0.5,
2-[(3ЈaS,4ЈR,7ЈR,7ЈaR)-Hexahydro-7Ј-hydroxy-2Ј,2Ј-dimethyl-5Ј-[4-
(2-methylbenzyloxy)phenylsulfonyl]-1Ј,3Ј-dioxolo[4,5-c]pyridin-4Ј-yl-
]acetohydroxamic Acid (4b): Following the general procedure 0.38 g
(86%) of 4b was obtained as a pale yellow solid m.p. 172–173 °C.
[α]2D5 = –19.25 (c = 0.4, MeOH). FT-IR (ATR): ν = 3418, 3258,
MeOH). FT-IR (ATR): ν = 3400–3200, 1732, 1591, 1151, 682,
˜
˜
1
609 cm–1. H NMR ([D6]DMSO): δ = 1.25 (s, 3 H, CH3), 1.39 (s,
1
1665, 1591, 1150, 745, 617 cm–1. H NMR ([D6]DMSO): δ = 1.25
3 H, CH3), 2.50–2.52 (m, 1 H, Ha-2Ј), 2.84 (dd, J = 16.2, 7.8 Hz,
1 H, Hb-2Ј), 2.99 (dd, J = 13.2, 10.5 Hz, 1 H, Ha-6), 3.37–3.39 (m,
1 H, Hb-6), 3.43–3.48 (m, 1 H, 7-H), 3.53 (s, 3 H, OCH3), 4.25–
4.27 (m, 1 H, 4-H), 4.28–4.33 (m, 2 H, 3a-H, 7a-H), 5.23 (s, 2 H,
-CH2-C6H4), 7.23 (d, J = 8.8 Hz, 2 H, ArH), 7.41–7.47 (m, 3 H,
ArH), 7.45–7.56 (m, 1 H, ArH), 7.76 (d, J = 8.8 Hz, 2 H, ArH)
ppm. 13C NMR ([D6]DMSO): δ = 24.6 (CH3), 25.4 (CH3), 36.0 (C-
2Ј), 42.3 (C-6), 50.1 (C-4), 51.3 (OCH3), 63.9 (C-7), 68.8 (-CH2-
C6H4), 72.7, 73.3 (C-3a, C-7a), 108.4 (C-2), 115.5, 126.4, 127.5,
128.0, 129.1, 130.4 (ArCH), 131.1, 133.2, 138.8, 161.5 (ArC), 170.9
(O=C) ppm. C24H28ClNO8S (525.99): calcd. C 54.80, H 5.37, N
2.66; found C 54.73, H 5.26, N 2.54.
(s, 3 H, CH3), 1.42 (s, 3 H, CH3), 2.34 (s, 3 H, H3C-C6H4), 2.51–
2.53 (m, 2 H, 2-H), 3.01 (dd, J = 14.3, 12.3 Hz, 1 H, Ha-6Ј), 3.29–
3.35 (m, 2 H, Hb-6Ј, 7Ј-H), 4.17–4.22 (m, 1 H, 4Ј-H), 4.23–4.33 (m,
2 H, 3Јa-H, 7Јa-H), 5.03 (d, J = 5.6 Hz, 1 H, OH), 5.19 (s, 2 H,
-CH2-C6H5), 7.23 (d, J = 8.8 Hz, 2 H, ArH), 7.26–7.27 (m, 3 H,
ArH), 7.43–7.44 (m, 1 H, ArH), 7.77 (d, J = 8.8 Hz, 2 H, ArH),
8.72, 10.37 (2 s, 2 H, NH and OH) ppm. 13C NMR ([D6]DMSO):
δ = 18.4 (H3C-C6H4), 24.6 (CH3), 25.8 (CH3), 34.2 (C-2), 42.6 (C-
6Ј), 49.9 (C-4Ј), 63.9 (C-7Ј), 68.4 (-CH2-C6H5), 72.9, 73.3 (C-3Јa,
C-7Јa), 108.0 (C-2Ј), 115.3, 128.7, 129.3, 130.2 (ArCH), 130.7,
134.1, 136.7, 161.8 (ArC), 166.5 (O=C) ppm. ESI MS: m/z = 507.4
[M + 1]+. C24H30N2O8S (506.57): calcd. C 56.90, H 5.97, N 5.53;
found C 56.83, H 5.76, N 5.28.
Methyl (3aS,4R,7R,7aR)-2-[Hexahydro-7-hydroxy-5-(4-methoxy-
phenylsulfonyl)-2,2-dimethyl-1,3-dioxolo[4,5-c]pyridin-4-yl]acetate
(16f): Following the general procedure 0.33 g (80%) of 16f was ob-
tained as colorless viscous oil. [α]2D5 = –20.6 (c = 0.5, MeOH). FT-
2-[(3ЈaS,4ЈR,7ЈR,7ЈaR)-5Ј-[4-(4-Bromobenzyloxy)phenylsulfonyl]-
hexahydro-7Ј-hydroxy-2Ј,2Ј-dimethyl-1Ј,3Ј-dioxolo[4,5-c]pyridin-4Ј-
yl]acetohydroxamic Acid (4c): Following the general procedure
0.35 g (71%) of 4c was obtained as a white solid m.p. 193–194 °C.
IR (ATR): ν = 3499, 1733, 1596, 1150, 805, 672 cm–1. 1H NMR
˜
([D6]DMSO): δ = 1.25 (s, 3 H, CH3), 1.39 (s, 3 H, CH3), 2.51–2.53
(m, 1 H, Ha-2Ј), 2.83 (dd, J = 16.3, 8.2 Hz, 1 H, Hb-2Ј), 2.99 (dd,
J = 13.1, 10.4 Hz, 1 H, Ha-6), 3.33–3.45 (m, 2 H, Hb-6, 7-H), 3.55
(s, 3 H, CO2CH3), 3.86 (s, 3 H, OCH3), 4.24–4.26 (m, 1 H, 4-H),
4.28–4.32 (m, 2 H, 3a-H, 7a-H), 5.14 (d, J = 5.3 Hz, 1 H, OH),
7.14 (d, J = 8.8 Hz, 2 H, ArH), 7.75 (d, J = 8.8 Hz, 2 H, ArH)
ppm. 13C NMR ([D6]DMSO): δ = 24.5 (CH3), 25.4 (CH3), 36.1 (C-
2Ј), 42.4 (C-6), 50.1 (C-4), 51.3 (CO2CH3), 55.7 (OCH3), 63.8 (C-
7), 72.7, 73.2 (C-3a, C-7a), 108.4 (C-2), 114.7, 129.1, (ArCH),
130.6, 162.7 (ArC), 170.9 (O=C) ppm. C18H25NO8S (415.46):
calcd. C 52.04, H 6.07, N 3.37; found C 51.75, H 5.99, N 3.18.
[α]2D5 = –20.75 (c = 0.4, MeOH). FT-IR (ATR): ν = 3509, 3247,
˜
1
1645, 1589, 1153, 723, 634 cm–1. H NMR ([D6]DMSO): δ = 1.25
(s, 3 H, CH3), 1.42 (s, 3 H, CH3), 2.50–2.53 (m, 2 H, 2-H), 3.01
(dd, J = 14.4, 12.38 Hz, 1 H, Ha-6Ј), 3.28–3.39 (m, 2 H, Hb-6Ј, 7Ј-
H), 4.16–4.21 (m, 1 H, 4Ј-H), 4.22–4.36 (m, 2 H, 3Јa-H, 7Јa-H),
5.02 (d, J = 5.3 Hz, 1 H, OH), 5.19 (s, 2 H, -CH2-C6H5), 7.20 (d,
J = 8.8 Hz, 2 H, ArH), 7.45 (d, J = 8.5 Hz, 2 H, ArH), 7.62 (d, J
= 8.5 Hz, 2 H, ArH), 7.76 (d, J = 8.8 Hz, 2 H, ArH), 8.71, 10.36
(2 s, 2 H, NH and OH) ppm. 13C NMR ([D6]DMSO): δ = 24.6
(CH3), 25.8 (CH3), 34.2 (C-2), 42.6 (C-6Ј), 49.9 (C-4Ј), 63.9 (C-7Ј),
69.9 (-CH2-C6H5), 72.9, 73.3 (C-3Јa, C-7Јa), 108.0 (C-2Ј), 115.3,
129.3, 130.0, 131.4 (ArCH), 121.3, 130.1, 135.7, 161.5 (ArC), 166.5
(O=C) ppm. ESI MS: m/z = 572.2 [M + 1]+. C23H27BrN2O8S
(571.44): calcd. C 48.34, H 4.76, N 4.90; found C 47.98, H 4.69, N
4.76.
General Procedure for the Synthesis of [(3ЈaS,4ЈR,7ЈR,7ЈaR)-5Ј-(4-
Arylsulfonyl)-7Ј-hydroxy-2Ј,2Ј-dimethyl-1Ј,3Ј-dioxolo[4,5-c]pyridine-
4Ј-yl]acetohydroxamic Acid Derivatives 4a–f: A solution of 1.25
NH2OK (2 mL; prepared from NH2OH·HCl and KOH as de-
scribed in the literature[13]) was added dropwise to a stirred solution
of the appropriate methyl ester 16a–f (0.86 mmol) in methanol
(4 mL). The resulting reaction mixture was stirred at room tem-
perature for 18 h. The solvent was evaporated under reduced pres-
sure and the residue was recrystallized from chloroform to give 4a–
f.
2-[(3ЈaS,4ЈR,7ЈR,7ЈaR)-Hexahydro-7Ј-hydroxy-2Ј,2Ј-dimethyl-5Ј-[4-
(4-nitrobenzyloxy)phenylsulfonyl]-1Ј,3Ј-dioxolo[4,5-c]pyridin-4Ј-yl]-
acetohydroxamic Acid (4d): Following the general procedure 0.36 g
(77%) of 4d was obtained as a yellow solid m.p. 138–140 °C. [α]2D5
= –23.75 (c = 0.4, MeOH). FT-IR (ATR): ν = 3442, 1663, 1594,
˜
1153, 702, 647 cm–1. 1H NMR ([D6]DMSO): δ = 1.25 (s, 3 H, CH3),
2-[(3ЈaS,4ЈR,7ЈR,7ЈaR)-5Ј-(4-Benzyloxyphenylsulfonyl)-hexahydro- 1.42 (s, 3 H, CH3), 2.50–2.54 (m, 2 H, 2-H), 2.97–3.03 (m, 1 H,
7Ј-hydroxy-2Ј,2Ј-dimethyl-1Ј,3Ј-dioxolo[4,5-c]pyridin-4Ј-yl]acetohy-
droxamic Acid (4a): Following the general procedure 0.3 g (71%)
of 4a was obtained as a white solid m.p. 173–175 °C. [α]2D5 = –20.25
Ha-6Ј), 3.27–3.33 (m, 2 H, Hb-6Ј, 7Ј-H), 4.17–4.20 (m, 1 H, 4Ј-H),
4.22–4.32 (m, 2 H, 3Јa-H, 7Јa-H), 5.03 (d, J = 5.3 Hz, 1 H, OH),
5.39 (s, 2 H, -CH2-C6H5), 7.23 (d, J = 8.8 Hz, 2 H, ArH), 7.75–
7.79 (m, 4 H, ArH), 8.28 (d, J = 8.8 Hz, 2 H, ArH), 8.71, 10.36 (2
(c = 0.4, MeOH). FT-IR (ATR): ν = 3515, 3443, 1667, 1589, 1152,
˜
704, 611 cm–1. 1H NMR ([D6]DMSO): δ = 1.25 (s, 3 H, CH3), 1.42 s, 2 H, NH and OH) ppm. 13C NMR ([D6]DMSO): δ = 24.6 (CH3),
(s, 3 H, CH3), 2.51–2.53 (m, 2 H, 2-H), 3.01 (dd, J = 14.3, 12.2 Hz, 25.8 (CH3), 34.1 (C-2), 42.5 (C-6Ј), 49.9 (C-4Ј), 63.9 (C-7Ј), 68.5
1 H, Ha-6Ј), 3.28–3.35 (m, 2 H, Hb-6Ј, 7Ј-H), 4.17–4.19 (m, 1 H, (-CH2-C6H5), 73.0, 73.3 (C-3Јa, C-7Јa), 108.1 (C-2Ј) 115.4, 123.7,
4Ј-H), 4.22–4.32 (m, 2 H, 3Јa-H, 7Јa-H), 5.02 (d, J = 5.6 Hz, 1 H,
OH), 5.20 (s, 2 H, -CH2-C6H5), 7.21 (d, J = 8.8 Hz, 2 H, ArH),
7.35–7.49 (m, 5 H, ArH), 7.76 (d, J = 8.8 Hz, 2 H, ArH), 8.72,
128.4, 129.4 (ArCH), 131.1, 144.1, 147.2, 161.3 (ArC), 166.4 (O=C)
ppm. ESI MS: m/z = 538.3 [M + 1]+. C23H27N3O10S (537.54):
calcd. C 51.39, H 5.06, N 7.82; found C 51.01, H 4.87, N 7.56.
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Eur. J. Org. Chem. 2007, 3669–3675