A. Rossello et al. / Bioorg. Med. Chem. 12 (2004) 2441–2450
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(60%): Rf ¼ 0:37; mp 105–107 ꢁC; H NMR (CDCl3): d
1.48 (s, 9H), 3.69 (br s, 2H), 5.06 (s, 2H), 5.30 (s, 2H),
6.93–6.98 (m, 2H), 7.32–7.59 (m, 12H), 7.68–7.72 (m,
2H), 7.89–7.93 (m, 2H). Anal. (C32H33NO6S) C, H, N.
6.1.3.6. [(Benzyloxybenzyloxy)(1,10-biphenyl-4-ylsulfon-
yl)amino]acetic acid (19d). The title compound was
prepared from 17d following the general procedure. The
crude product was purified by chromatography on silica
gel using hexane–ethyl acetate 2/1 v/v to give 19d as a
1
solid (28%); mp 62–63 ꢁC; H NMR (CDCl3): d 3.83 (s,
6.1.3. General procedure for the preparation of carboxylic
acids (18a,b,d, 19a,c,d).
2H), 5.01 (s, 2H), 5.25 (s, 2H), 6.90–6.94 (m, 2H), 7.29–
7.57 (m, 12H), 7.65–7.70 (m, 2H), 7.87–7.91 (m, 2H).
Anal. (C28H25NO6S) C, H, N.
Trifluoroacetic acid (4.4 mL,
57 mmol) was added dropwise to a stirred and cooled
(0 ꢁC) solution of the appropriate tert-butyl ester 15,16
(1 mmol) in freshly distilled (P2O5) dichloromethane
(3.4 mL). The solution was stirred for 5 h at 0 ꢁC and the
solvent was then removed in vacuo to give pure 18a,b,d,
19a,c,d as solids.
6.1.4. General procedure for the preparation of O-
TBDMS acid hydroxyamides 20a,b,d, 21a,c,d.
1-[3-
(Dimethylamino)propyl]-3-ethyl carbodiimide hydro-
chloride (EDCI) was added portionwise (1 mmol) to a
stirred and cooled (0 ꢁC) solution of the carboxylic acid
18, 19 (1 mmol) and O-(tert-butyldimethylsilyl-hydrox-
ylamine (1 mmol) in freshly distilled (P2O5) dichlorom-
ethane (18 mL). After stirring at rt for 20 h, the mixture
was washed with water (20 mL) and the organic phase
was dried and evaporated in vacuo. The residue was
purified by flash chromatography to yield pure silyl
esters 20a,b,d, 21a,c,d as oils.
6.1.3.1. {Isopropoxy[(4-methoxyphenyl)sulfonyl]amino}-
acetic acid (18a). The title compound was prepared from
16a following the general procedure. The crude product
18a was used without further purification: a yellow oil
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(99%); H NMR (CDCl3): d 1.23 (d, J ¼ 6:2 Hz, 6H),
3.74 (s, 2H), 3.89 (s, 3H), 4.52 (septet, J ¼ 6:2 Hz, 1H),
7.01–7.05 (m, 2H), 7.80–7.83 (m, 2H). Anal.
(C12H17NO6S) C, H, N.
6.1.4.1.
2-{Isopropoxy[(4-methoxyphenyl)sulfonyl]-
amino}acetic acid (tert-butyldimethylsilyl)hydroxyamide
(20a). The title compound was prepared from 18a fol-
lowing the general procedure. The crude oil 20a (75%)
was used without further purification; 1H NMR
(CDCl3): d 0.20 (s, 6H), 0.97 (s, 9H), 1.22 (d, J ¼ 6:2 Hz,
6H), 3.66 (s, 2H), 3.89 (s, 3H), 4.41 (septet, J ¼ 6:2 Hz,
1H), 7.01–7.05 (m, 2H), 7.78–7.82 (m, 2H), 8.59 (br s,
1H). Anal. (C18H32N2O6SSi) C, H, N.
6.1.3.2. {Ethyloxy[(4-methoxyphenyl)sulfonyl]amino}-
The title compound was prepared
acetic acid (18b).
from 16b following the general procedure. The crude
product 18b was used without further purification: a
yellow oil (99%); 1H NMR (CDCl3): d 1.15 (t,
J ¼ 7:1 Hz, 3H), 3.76 (s, 2H), 3.89 (s, 3H), 4.28 (q,
J ¼ 7:1 Hz, 2H), 7.01–7.06 (m, 2H), 7.79–7.83 (m, 2H).
Anal. (C11H15NO6S) C, H, N.
6.1.4.2. 2-{Ethyloxy[(4-methoxyphenyl)sulfonyl]amino}-
acetic acid (tert-butyldimethylsilyl)hydroxyamide (20b).
The title compound was prepared from 18b following
the general procedure. The crude product was purified
by flash chromatography on silica gel using hexane–
ethyl acetate 1/1 v/v to give 20b as a yellow oil (20%): 1H
NMR (CDCl3): d 0.20 (s, 6H), 0.97 (s, 9H), 1.19 (t,
J ¼ 7:1 Hz, 3H), 3.62 (s, 2H), 3.89 (s, 3H), 4.21 (q,
J ¼ 7:1 Hz, 2H), 6.98–7.01 (m, 2H), 7.77–7.82 (m, 2H).
Anal. (C17H30N2O6SSi) C, H, N.
6.1.3.3. {Benzyloxybenzyloxy[(4-methoxyphenyl)sulfon-
yl]amino}acetic acid (18d).
The title compound was
prepared from 16d following the general procedure. The
crude product 18d was used without further purification:
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a yellow solid (96%); H NMR (CDCl3): d 3.78 (s, 2H),
3.85 (s, 3H), 5.04 (s, 2H), 5.21 (s, 2H), 5.40 (br s, 1H),
6.92–7.00 (m, 4H), 7.28–7.40 (m, 7H), 7.77–7.81 (m,
2H). Anal. (C23H23NO7S) C, H, N.
6.1.3.4. [(Isopropoxy)(1,10-biphenyl-4-ylsulfonyl)amino]-
acetic acid (19a). The title compound was prepared from
17a following the general procedure. The crude product
19a was used without further purification: a yellow solid
6.1.4.3. 2-{Benzyloxybenzyloxy[(4-methoxyphenyl)sul-
fonyl]amino}acetic acid (tert-butyldimethylsilyl)hydroxy-
amide (20d). The title compound was prepared from 18d
following the general procedure. The crude oil 20d
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(86%); mp 125–127 ꢁC; H NMR (CDCl3): d 1.26 (d,
1
J ¼ 6:2 Hz, 6H), 3.82 (s, 2H), 4.58 (septet, J ¼ 6:2 Hz,
1H), 7.43–7.64 (m, 5H), 7.76–7.80 (m, 2H), 7.92–7.96
(m, 2H). Anal. (C17H19NO5S) C, H, N.
(67%) was used without further purification; H NMR
(CDCl3): d 0.17 (s, 6H), 0.97 (s, 9H), 3.57 (s, 2H), 3.86
(s, 3H), 5.06 (s, 2H), 5.09 (s, 2H), 6.95–7.00 (m, 4H),
7.31–7.41 (m, 7H), 7.76–7.81 (m, 2 H), 8.16 (br s, 1H).
Anal. (C29H38N2O7SSi) C, H, N.
6.1.3.5. [(Allyloxy)(1,10-biphenyl-4-ylsulfonyl)amino]-
acetic acid (19c).
The title compound was prepared
from 17c following the general procedure. The crude
product 19c was used without further purification: a
pale yellow solid (92%); mp 150–152 ꢁC; 1H NMR
(CDCl3): d 3.86 (s, 2H), 4.81 (d, J ¼ 6:2 Hz, 2H), 5.23–
5.37 (m, 2H), 5.81–6.01 (m, 1H), 7.43–7.63 (m, 5H),
7.76–7.80 (m, 2H), 7.92–7.96 (m, 2H). Anal.
(C17H17NO5S) C, H, N.
6.1.4.4. [(Isopropoxy)(1,10-biphenyl-4-ylsulfonyl)amino]-
acetic acid (tert-butyldimethylsilyl)hydroxyamide (21a).
The title compound was prepared from 19a following
the general procedure. The crude oil 21a (58%) was used
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without further purification; H NMR (CDCl3): d 0.20
(s, 6H), 0.90 (s, 9H), 1.26 (d, J ¼ 6:2 Hz, 6H), 3.71 (s,
2H), 4.50 (septet, J ¼ 6:2 Hz, 1H), 7.42–7.64 (m, 5H),