J. D. Park, D. H. Kim / Bioorg. Med. Chem. 12 (2004) 2349–2356
2353
All chemicals were of reagent grade obtained from Al-
drich Chemical Co. Dichloromethane, toluene, and
dimethylformamide were distilled over calcium hydride
and stored under nitrogen. Tetrahydrofuran was dis-
tilled over sodium-benzophenone before use.
over anhydrous MgSO4. The residue that was obtained
by evaporation of the dried solution was purified by
column chromatography (EtOAc/n-hexane ¼ 1:4) to give
the product (5.6 g, 71.5%) as a white solid. Mp 75–76 ꢁC;
1
IR (CHCl3) 1133, 1324, 1734 cmꢁ1; H NMR 300 MHz
(CDCl3) d 1.23 (s, 9H), 2.81 (m, 1H), 3.05 (m, 2H), 3.21
(m, 1H), 3.53 (dd, 1H), 3.65 (s, 3H), 4.06 (s, 1H), 7.14–
7.31 (m, 5H); 13C NMR 300 MHz (CDCl3) d 30.4, 38.4,
43.8, 52.6, 55.3, 56.4, 127.5, 129.2, 129.5, 137.4, 174.2.
Anal. Calcd for C15H23NO4S: C, 57.48; H, 7.40; N, 4.47.
Found: C, 57.20; H, 7.56; N, 4.59.
4.1. 3-Phenyl-2-sulfamoyloxypropaonic acid benzyl
ester (9)
Formic acid (0.67 mL, 17.2 mmol) was added dropwise
to neat chlorosulfonyl isocyanate (1.5 mL, 17.2 mmol) at
0 ꢁC with rapid stirring. Vigorous gas evolution was
observed during the addition. The resulting viscous
suspension was stirred for 5 min at 0 ꢁC. methylene
chloride was added and the solution was stirred for 1 h
at 0 ꢁC, and then for 4 h at 25 ꢁC. To the solution was
slowly added a mixture of (S)-phenyllactic acid benzyl
ester (2.95 g, 11.5 mmol) and pyridine (1.4 mL,
17.3 mmol) at 0 ꢁC. The resulting solution was stirred for
12 h. After evaporation of the solvent, the residue was
dissolved in ethyl acetate (50 mL), washed successively
with 1 N HCl solution (30 mL · 3) and brine (30 mL · 3),
and dried over anhydrous MgSO4. The dried solution
was concentrated in vacuo to give the product (2.2 g,
4.4. 2-Benzyl-3-tert-butylsulfamoylpropaonic acid (12)
To a solution of 11 (1.5 g, 4.8 mmol) in methanol
(15 mL), was added 2 N NaOH solution (2.4 mL) and
the resulting solution was stirred for 12 h. After evapo-
ration of the solvent, the residue was dissolved in 1 N
HCl solution and the solution was extracted with ethyl
acetate (30 mL · 3). The extract was dried over anhy-
drous MgSO4 and evaporated under reduced pressure to
give the product (0.75 g, 52.3%) as an oil, which solidi-
fied on standing. Mp 119–120 ꢁC; IR (CHCl3) 1125,
1
1311, 1717 cmꢁ1; H NMR 300 MHz (CDCl3) d 1.22 (s,
57%) as a white solid. Mp 86.5–87 ꢁC; ½aꢀ20 )25.7 (c 1.04,
9H), 2.82 (dd, 1H), 3.04 (dd, 2H), 3.13–3.50 (m, 2H),
3.53 (dd, 1H), 4.43 (s, 1H), 7.20–7.44 (m, 5H); 13C NMR
300 MHz (CD3OD) d 29.3, 37.9, 43.7, 54.0, 55.8, 127.0,
128.7, 129.4, 138.1, 175.8. Anal. Calcd for C15H23NO4S:
C, 56.16; H, 7.07; N, 4.68. Found: C, 56.17; H, 6.97; N,
4.70.
D
MeOH); IR (neat) 1186, 1385, 1745 cmꢁ1
;
1H NMR
300 MHz (CDCl3) d 3.14–3.24 (m, 2H), 5.02 (s, 2H),
5.13–5.18 (m, 3H), 7.13–7.35 (m, 5H); 13C NMR
300 MHz (CDCl3) d 38.4, 68.3, 79.8, 127.9, 129.0, 129.1,
129.2, 129.3, 130.0, 134.9, 135.0, 169.7. Anal. Calcd for
C16H17NO5S: C, 57.30; H, 5.11; N, 4.18. Found: C,
57.24; H, 4.78; N, 4.20.
4.5. 2-Benzyl-3-sulfamoylpropaonic acid (3)
4.2. 3-Phenyl-2-sulfamoyloxypropanoic acid (2)
Compound 12 (0.75 g, 2.51 mmol) was dissolved in tri-
fluoroacetic acid (5 mL) and the resulting solution was
stirred for 12 h, then evaporated under reduced pressure,
and the residue was recrystallized from ethyl acetate and
n-hexane to give the product (0.58 g, 95%) as a white
solid. Mp 98–100 ꢁC; IR (CHCl3) 1121, 1325, 1717,
3446 cmꢁ1; 1H NMR 300 MHz (CDCl3) d 2.83 (dd, 1H),
3.06–3.19 (m, 2H), 3.27 (dd, 1H), 3.59 (dd, 1H), 5.30 (br,
2H), 7.16–7.61 (m, 5H), 9.02 (s, 1H); 13C NMR
300 MHz (CDCl3) d 37.8, 43.3, 55.4, 126.9, 128.6, 129.3,
138.0, 175.6. Anal. Calcd for C15H23NO4SÆ1/2 H2O: C,
48.47; H, 5.49; N, 5.65. Found: C, 48.74; H, 5.21; N,
5.73.
A solution of 9 (1.0 g, 3 mmol) in anhydrous MeOH
(25 mL) was stirred under hydrogen atmosphere in the
presence of 10% Pd–C (30 mg) for 2 h. The resulting
mixture was filtered and the filtrate was evaporated
under reduced pressure to give the product (0.73 g, 99%)
20
D
as a white product. Mp 109–111 ꢁC; ½aꢀ )10.1 (c 1.61,
MeOH); IR (neat) 1183, 1368, 1734 cmꢁ1
;
1H NMR
300 MHz (CD3OD) d 3.15 (d, 2H), 4.99 (m, 1H), 7.25
(m, 5H); 13C NMR 300 MHz (CD3OD) d 38.4, 79.5,
127.0, 128.4, 129.7, 135.8, 170.2. Anal. Calcd for
C9H11NO5S: C, 44.08; H, 4.52; N, 5.71. Found: C,
43.72; H, 4.31; N, 5.61.
4.6. (S)-2-(2-Oxo-oxazolidine-3-sulfonylamino)-3-phenyl-
propaonic acid benzyl ester ((S)-13)
4.3. 2-Benzyl-3-tert-butylsulfamoylpropnonic acid
methyl ester (11)
To an ice-chilled solution of chlorosulfonyl isocyanate
(2 mL, 23 mmol) in methylene chloride (25 mL) was
added 2-chloroethanol (1.54 mL, 23 mmol) and stirred
at 0 ꢁC for 1.5 h. To the resulting mixture was added a
solution of phenylalanine benzyl ester p-toluenesulfo-
nate (9.83 g, 23 mmol) and triethylamine (9.62 mL,
69 mmol) obtained by dissolving in CH2Cl2 (100 mL).
The temperature was remained under 5 ꢁC during the
addition. The resulting solution was allowed to warm to
room temperature and stirred for 12 h. The reaction was
To a suspension of 109 (7 g, 25 mmol) in toluene was
added PCl5 (5.2 g, 25 mmol) and the resulting suspension
was stirred for 2 h. The suspension was filtered off and
the filtrate was cooled to 0 ꢁC. ttert-Butylamine (5.7 mL,
75 mmol) was added slowly to the filtrate at 0 ꢁC and the
resulting clear solution was stirred for 1 h. The solution
was evaporated under reduced pressure and the residue
was dissolved in ethyl acetate, washed with 1 N HCl
solution (30 mL · 3) and brine (30 mL · 3), and dried