7996
J. E. Baldwin et al. / Tetrahedron 57 02001) 7991±7997
0.33, CH2Cl2); nmax/cm21 2KBr) 1752 and 1734 22£ester
CvO) and 1642 2amide CvO); dH 2200 MHz; CDCl3)
2major rotamer) 1.39 29H, s, CO2But), 2.63 and 2.77 2each
1H, dd, J17.5, 7.5 Hz, CH2CO2But), 3.15±3.21 21H, m,
3-H), 3.73 and 4.23 [each 1H, dd 2J11.5, 3.5 Hz) and dd
2J11.5, 5.5 Hz), 5-H2], 3.80 23H, s, CO2Me), 4.45 21H, d,
J8 Hz, 2-H), 4.69±4.76 21H, m, 4-H), 6.95 21H, t, J5 Hz,
50-H), 7.32±7.41 23H, m, PhH), 7.53±7.58 23H, m, PhH) and
8.45 22H, d, J5 Hz, 40- and 60-H); dC 250 MHz; CDCl3)
27.95 [CO2C2CH3)3], 34.94 2CH2CO2But), 41.84 23-C),
46.85 2CO2Me), 52.54 22-C), 56.15 25-C), 63.26 24-C),
81.17 [CO2C2CH3)3], 117.02 250-C), 126.62, 127.46,
128.25, 128.44, 130.43 2COPh and 20-C), 157.39 240- and
60-C), 169.68, 170.25 and 171.60 2CO2But, CO2M e and
COPh); m/z 2CI) 458 2MH1, 100%) and 402
2C19H20N3O5S1, 46). Found: MH1 458.1755. C23H27N3O5S
requires MH1 458.1750.
solved in diethyl ether. The ethereal phase was washed
with water, dried 2MgSO4) and evaporated to a brown oil.
The material was subjected to silica-gel column chromato-
graphy [CH2Cl2±EtOAc 219:1) as eluent], which afforded
one major fraction. The eluted material, obtained as a pale-
yellow oil 20.029 g, 25%), was identi®ed as the title
compound 10f; [a]D132.0 2c 0.50, CH2Cl2); nmax/cm21
2KBr) 1723 2ester CvO) and 1640 2amide CvO); dH
2400 MHz; CDCl3) 2major rotamer) 1.42 29H, s, CO2But),
2.75 and 2.91 [each 1H, dd 2J17.5, 5.5 Hz) and dd
2J17.5, 9.5 Hz), CH2CO2But], 3.03±3.08 21H, m, 3-H),
3.66 and 3.96 [each 1H, dd 2J11.5, 1.5 Hz) and dd
2J11.5, 4.5 Hz), 5-H2], 3.81 23H, s, CO2Me), 4.12±4.14
21H, m, 4-H), 4.53 21H, d, J9 Hz, 2-H) and 7.32±7.81
212H, m, PhH and Ar-H); dC 2100 MHz; CDCl3) 2major
rotamer) 28.00 [CO2C2CH3)3], 34.44 2CH2CO2But), 42.94
23-C), 51.29 and 52.57 24-C and CO2Me), 55.58 25-C), 62.48
22-C), 81.25 [CO2C2CH3)3], 126.56, 126.66, 127.35, 127.39,
127.61, 128.24, 128.44, 128.93, 129.65, 130.33, 130.44,
131.96, 132.46, 133.49 and 135.23 2COPh and napthyl-C),
and 170.00, 170.62 and 171.76 2CO2But, CO2Me and
COPh); m/z 2CI) 506 2MH1, 60%) and 450
2C25H24NO5S1, 100). Found: MH1 506.1984. C29H31NO5S
requires MH1 506.2001.
4.1.8. +2S,3S,4S)-4-+Benzothiazol-2-ylsulfanyl)-1-benzoyl-
3-tert-butoxycarbonylmethylpyrrolidine-2-carboxylic
acid methyl ester 10e. To a stirred solution of 22S,3S,4R)-1-
benzoyl-3-tert-butoxycarbonylmethyl-4-methanesulfonyl-
oxypyrrolidine-2-carboxylic acid methyl ester 9 20.190 g,
0.43 mmol) in dimethyl sulfoxide 25 cm3) was added
2-mercaptobenzothiazole
sodium
salt
20.320 g,
1.69 mmol). The solution was heated at 908C for 1 h, and
then cooled to ambient temperature. The reaction mixture
was then poured onto saturated brine, and extracted with
dichloromethane. The combined organic extracts were
concentrated and redissolved in diethyl ether. The ethereal
phase was washed with water, dried 2MgSO4) and evapo-
rated to a yellow solid 20.263 g). The material was subjected
to silica-gel column chromatography 2CH2Cl2 as eluent),
which afforded one major fraction. The eluted material,
obtained as a clear, colourless oil 20.116 g, 53%), was
identi®ed as the title compound 10e; [a]D142.3 2c 0.80,
CH2Cl2); nmax/cm21 2KBr) 1729 2ester CvO) and 1640
2amide CvO); dH 2200 MHz; CDCl3) 2major rotamer)
1.38 29H, s, CO2But), 2.63±2.87 22H, m, CH2CO2But),
3.16±3.31 21H, m, 3-H), 3.81 23H, s, CO2Me), 3.90 and
4.29 [each 1H, dd 2J11.5, 2 Hz) and dd 2J11.5, 5 Hz),
5-H2], 4.46 21H, d, J9 Hz, 2-H), 4.84±4.93 21H, m, 4-H),
and 7.18±7.90 29H, m, PhH and 4£Ar-H); dC 250 MHz;
CDCl3) 2major rotamer) 27.92 [CO2C2CH3)3], 34.96
2CH2CO2But), 42.45 23-C), 50.34 and 52.63 22-C and
CO2Me), 56.45 25-C), 62.86 24-C), 81.43 [CO2C2CH3)3],
120.97, 121.86, 124.64, 126.11, 127.43, 128.31, 128.39,
130.59, 134.88 2COPh and 4£Ar-C), 170.00 and 171.43
2CO2But, CO2Me and COPh); m/z 2CI) 513 2MH1, 30%)
and 457 2C22H21N2O5S21, 100). Found: MH1 513.1517.
C26H28N2O5S2 requires MH1 513.1518.
4.1.10.
+2S,3S,4S)-3-Carboxymethyl-4-+1-methyl-1H-
imidazol-2-ylsulfanyl)pyrrolidine-2-carboxylic acid 11a.
To 22S,3S,4S)-1-benzoyl-3-tert-butoxycarbonylmethyl-4-21-
methyl-1H-imidazol-2-ylsulfanyl) pyrrolidine-2-carboxylic
acid methyl ester 10a 20.050 g, 0.109 mmol) was added
3
6 Mhydrochloric acid 22 cm ). The mixture was heated at
re¯ux for 16 h. The resulting solution was then cooled to
ambient temperature, washed with dichloromethane, and
evaporated to an off-white solid 20.033 g). The residue
was dissolved in water 210 cm3) and loaded onto a pre-
activated column of acidic ion exchange resin 2Dowexw
50WX8-100). After ¯ushing the column with water
2100 cm3), the compound was eluted with 2 Maqueous
ammonia solution 2100 cm3). The resulting solution was
evaporated to give the title compound 11a 20.024 g, 77%);
[a]D164.1 2c 0.46, H2O); nmax/cm21 2KBr) 3500±2000
2brs), 1622 2brs) and 1394 2s); dH 2400 MHz; D2O) 2.45 and
2.72 [each 1H, dd 2J16.5, 11 Hz) and dd 2J16.5, 4.5 Hz),
CH2CO2H], 2.77±2.85 21H, m, 3-H), 3.37 and 3.50 [each
1H, d 2J12.5 Hz) and dd 2J12.5, 5 Hz), 5-H2], 3.62 23H,
s, NMe), 3.77 21H, d, J10.5 Hz, 2-H), 4.05 21H, t, J5 Hz,
4-H), 6.97 and 7.16 21H, s, imidazole 4- and 5-H); dC
250 MHz; D2O) 33.47 and 36.61 2NMe and CH2CO2H),
44.20 23-C), 50.50, 51.14 22- and 5-C), 63.50 24-C),
125.17, 128.64 2Ar 4- and 5-C), 137.08 2Ar 2-C), 173.55
and 178.62 22£CO2H); m/z 2CI) 286 2MH1, 100%). Found:
MH1 286.0858. C11H15N3O4S requires MH1 286.0862.
4.1.9. +2S,3S,4S)-1-Benzoyl-3-tert-butoxycarbonylmethyl-
4-+napthalen-2-ylsulfanyl)pyrrolidine-2-carboxylic acid
methyl ester 10f. To a stirred solution of 22S,3S,4R)-1-
benzoyl-3-tert-butoxycarbonylmethyl-4-methanesulfonyl-
oxypyrrolidine-2-carboxylic acid methyl ester 9 20.100 g,
0.23 mmol) in dimethyl sulfoxide 25 cm3) was added 2-
thionapthol sodium salt 20.206 g, 1.13 mmol). The solution
was heated at 908C for 6 h, and then cooled to ambient
temperature. The reaction mixture was then poured onto
saturated brine, and extracted with dichloromethane. The
combined organic extracts were concentrated and redis-
4.1.11. +2S,3S,4S)-3-Carboxymethyl-4-phenylsulfanyl-
pyrrolidine-2-carboxylic acid 11b. To 22S,3S,4S)-1-
benzoyl-3-tert-butoxycarbonylmethyl-4-phenylsulfanylpyr-
rolidine-2-carboxylic acid methyl ester 10b 20.027 g,
0.059 mmol) was added 6 Mhydrochloric acid 22 cm 3).
The reaction mixture was heated at re¯ux for 5 h. The
resulting solution was then cooled to ambient temperature,
washed with dichloromethane, and evaporated to an off-
white solid. The residue was dissolved in water 210 cm3)
and loaded onto a pre-activated column of acidic ion