Moreau and Campagne
(6R)-3-Iod o-6-m eth yl-5,6-d ih yd r op yr a n -2-on e (14b): 1H
NMR (CDCl3, 300 MHz) δ 1.45 (d, J ) 6.3 Hz, 3H), 2.41 (m,
128.3, 128.5, 136.3, 148.1, 155.6, 164.7, 169.2. (E isomer) 14.2,
20.4, 27.9, 35.7, 37.9, 55.1, 55.3, 61.4, 66.9, 72.6, 82.7, 95.0,
128.1, 128.3, 128.5, 136.3, 144.7, 155.6, 164.7, 169.2; IR (KCl,
cm-1) ν 1037, 1154, 1247, 1506, 1718, 2339, 2360, 2933, 2977;
ESI-MS m/z 550.3 (M + K+), 534.3 (M + Na+), 478.4; HRMS
ES+ calcd for C25H37NO8SNa 534.2137 (M + Na), found
534.2163.
2H), 4.68 (m, 1H), 7.53 (∼dd, J ) 3.5 Hz, J ) 5.4 Hz, 1H); 13
C
NMR (CDCl3,75 MHz) δ 20.8, 35.4, 75.5, 89.8, 154.0, 160.8;
IR (KCl, cm-1) ν 669, 756, 1215, 3020; MS (IE) m/z 238 (M•+),
194, 166, 68, 43, 41; mp 68-69 °C. Anal. Calcd for C6H7IO2:
C, 30.28; H, 2.96. Found: C, 30.44; H, 2.96.
(2Z,5R)-5-[(2S)2-ter t-Bu toxyca r bon yla m in o-3-m er ca p -
top r op ion yloxy]-2-iod oh ex-2-en oic Acid Eth yl Ester (16).
To a solution of 15 (110 mg, 0.15 mmol) and triethylsilane (27
µL, 0.17 mmol) in CH2Cl2 (1.5 mL) was added TFA (60 µL, 4%
v/v). The mixture was stirred for 40 min and treated with
saturated NaHCO3 solution. After extraction with CH2Cl2, the
organic layers were washed with brine and dried over MgSO4,
and the solvent was evaporated under reduced pressure.
Chromatography on silica gel (2/1 heptane/ethyl acetate) gave
16 (66 mg, 90% yield) as a colorless oil: 1H NMR (CDCl3, 300
MHz) δ 1.23-1.32 (m, 6H), 1.39 (s, 9H), 2.56 (m, 2H), 2.91 (m,
2H), 4.21 (q, J ) 7.1 Hz, 2H), 4.51 (bs, 1H), 5.13 (∼sext, J )
6.15 Hz, 1H), 5.35 (bs, 1H), 7.13 (∼q, J ) 6.7 Hz, 1H); 13C NMR
(CDCl3,75 MHz) 14.5, 20.3, 27.7, 28.5, 43.4, 55.3, 63.3, 71.2,
80.7, 98.8, 147.5, 155.4, 162.9, 170.1; IR (KCl, cm-1) ν 756,
1165, 1250, 1367, 1499, 1715, 2980, 3429; ESI-MS m/z 526 (M
+ K+), 510 (M + Na+), 488.1 (M + H+), 387.9, 130.3; HRMS
ES+ calcd for C16H26INO6S 510.04233 (M + Na+), found
510.04183.
Z-D-cystein e-O-t-Bu (18). To a solution of Z-D-cystine-O-
t-Bu23 (510 mg, 0.82 mmol) in THF/H2O (10/1) (7 mL) was
added tributyl phosphine (234 µL, 0.92 mmol). The mixture
was stirred for 5 min at room temperature, and the solvent
was removed under reduced pressure. Chromatography on
silica gel (heptane/ethyl acetate 3/1) gave 18 (500 mg, 98%
yield) as a white solid: 1H NMR (CDCl3, 300 MHz) δ 1.48 (s,
9H), 2.97 (bdd, J ) 3.4, 8.3 Hz, 2H), 4.54 (m, 1H), 5.11 (s, 2H),
5.76 (bd, J ) 6.2 Hz, NH), 7.35 (bs, 5H); 13C NMR (CDCl3,75
MHz) 27.2, 27.8, 55.3, 66.8, 82.7, 127.9, 128.0, 128.4, 136.0,
155.5, 168.7; IR (KCl, cm-1) ν 697, 1062, 1154, 1218, 1346,
1369, 1506, 1722, 3421; ESI-MS m/z 334.1 (M + Na+), 278.0.
Anal. Calcd for C15H21NO4S: C, 57.86; H, 6.80; N, 4.50.
Found: C, 58.03; H, 6.67; N, 4.21.
(2Z,5R)-2-((2S)2-Ben zyloxyca r bon yla m in o-2-ca r boxy-
th ylsu lfan yl)-5-h ydr oxyh ex-2-en oic Acid Eth yl Ester (20).
To a solution of 19 (98 mg, 0.19 mmol) in CH2Cl2 (1.2 mL)
were added triethylsilane (34 µL, 0.21 mmol) and TFA (0.8
mL) dropwise. The mixture was stirred for 2 h at room
temperature and treated with a saturated solution of NaHCO3.
After extraction with CH2Cl2, the aqueous layer was acidified
with a few drops of concentrated HCl and extracted with CH2-
Cl2, The organic layers were washed with brine and dried over
MgSO4, and the solvent was evaporated under reduced pres-
sure. The crude product (84 mg,74% yield) was directly used
for the next step.
(2Z,5R )-2-((2S )2-Be n zyloxyca r b on yla m in oa cr yloyl-
su lfa n yl)-5-h yd r oxyh ex-2-en oic Acid Eth yl Ester (21). To
a solution of crude material 20 (84 mg, 0.14 mmol) in CH2Cl2
(60 mL) were added triethylamine (51.5 µL, 0.36 mmol),
PyBroP (80 mg, 0.17 mmol), and DMAP (1.5 mg, 0.0018 mmol).
The mixture was stirred overnight at room temperature, and
the solvent was evaporated under reduced pressure. The crude
product was taken up in CH2Cl2 and treated with a saturated
solution of NaHCO3. After extraction with CH2Cl2, the organic
layers were washed with brine and dried over MgSO4, and the
solvent was evaporated under reduced pressure. Chromatog-
raphy on silica gel (3/1 heptane/ethyl acetate) gave 21 (28 mg,
61% yield) as an colorless oil (this compound could not be
separated from unidentified byproducts ∼10%): 1H NMR
(CDCl3, 300 MHz) δ 1.25 (d, 6.2 Hz, 3H), 1.29 (t, J ) 7.1 Hz,
3H), 2.54 (dd, J ) 6.1, 7.5 Hz, 2H), 4.01 (sext, J ) 6.1 Hz,
1H), 4.25 (q, J ) 7.1 Hz), 5.16 (s, 2H), 5.95 (bt, J ) 1.8 Hz),
6.51 (bd, J ) 1.8 Hz), 7.22 (bs, 1H), 7.37 (bs, 5H), 7.64 (t, J )
7.5 Hz); 13C NMR (CDCl3,75 MHz) δ 14.1, 23.5, 40.5, 62.0, 66.7,
67.2, 106.9, 123.4, 128.2, 128.4, 128.6, 135.6, 137.4, 152.4,
158.1, 171.1, 187.3; ESI-MS m/z 432.1 (M + K+), 416.2 (M +
Na+), 370.1, 130.4; HRMS ES+ calcd for C19H23NO6SNa
416.1144 (M + Na+), found 416.1146.
(2Z,5R)-2-((2S)2-Ben zyloxyca r b on yla m in o-2-ter t-b u -
toxyca r bon yleth ylsu lfa n yl)-5-h yd r oxyh ex-2-en oic Acid
Eth yl Ester (19). To a solution of 13 (175 mg, 0.53 mmol),
Pd2dba3 (13.7 mg, 0.013 mmol), and dppf (30 mg, 0.053 mmol)
in N-methylpyrrolidone (9 mL) was added triethylamine (150
µL, 1.06 mmol). The solution was stirred for 30 min at room
temperature and then warmed to 60 °C. Z-D-cysteine tert-butyl
ester (18) (231 mg, 0.74 mmol) in NMP (2.5 mL) was added
over 1 h 30. The mixture was stirred for an additional 2 h,
cooled at room temperature, and quenched with brine. After
extraction with EtOAc, the organic layers were washed with
brine and dried over MgSO4, and the solvent was evaporated
under reduced pressure. Chromatography on silica gel (7/1
pentane/acetone) gave 19 (170 mg, 63% yield) as an insepa-
rable Z/E mixture (80/20) and 15 mg of starting material
(6Z,3S,9R)-3-Ben zyloxyca r bon yla m in o-9-m eth yl-2-oxo-
3,4,8,9-tetr a h yd r o-2H-[1,5]oxa th ion in e-6-ca r boxylic Acid
Eth yl Ester (24). To a solution of crude material 23 (29 mg,
0.07 mmol) in THF (35 mL) were added triphenylphosphine
(55 mg, 0.21 mmol) and diisopropyl azodicarboxylate (43 µL,
0.21 mmol). The mixture was stirred overnight at reflux. The
solvent was removed under reduced pressure. Chromatography
on silica gel (3/1 heptane/ethyl acetate) gave 24 (16 mg, 58%
1
yield): H NMR (CDCl3, 300 MHz) δ 1.33 (t, J ) 7.1 Hz, 3H),
1.36 (d, J ) 6.7 Hz, 3H), 2.51 (m, 1H), 3.01 (m, 1H), 3.07 (dd,
J ) 5.3, 14.5 Hz, 1H), 3.33 (dd, J ) 3.3, 14.2 Hz, 1H), 4.26 (q,
J ) 7.1 Hz, 2H), 4.65 (m, 1H), 5.11 (s, 2H), 5.26 (m, 1H), 5.69
(bd, J ) 5.8 Hz), 7.36 (bs, 5H), 7.52 (dd, J ) 7.2, 7.8 Hz, 1H);
13C NMR (CDCl3,75 MHz) 14.3, 18.9, 34.8, 41.1, 54.2, 62.0,
67.1, 69.9, 128.2, 128.4, 128.7, 132.8, 136.2, 148.4, 155.5, 165.4,
171.1; IR (KCl, cm-1) ν 1056, 1194, 1253, 1357, 1514, 1713,
1741, 2928, 2981, 3419; ESI-MS m/z 432.1 (M + K+), 416.1
(M + Na+). Anal. Calcd for C19H23NO6S: C, 58.00; H, 5.89; N,
1
(8.5%): H NMR (CDCl3, 300 MHz) δ 1.13 (bd, 6.3 Hz, 0.6H),
1.20 (bd, 2.4H), 1.23 (t, J ) 7.1 Hz, 0.4H), 1.29 (t, J ) 7.1 Hz,
1.6H), 1.46 (s, 9H), 2.47-2.64 (m, 1H), 2.73-2.84 (m, 1H), 3.02
(dd, J ) 4.6, 13.2 Hz, 0.2H), 3.12 (dd, J ) 4.8, 14.4 Hz, 0.8H),
3.27 (m, 0.2H), 3.32 (m, 0.8H), 3.31 (s, 2.4H), 3.36 (s, 0.6H),
3.79 (m, 0.2H), 3.85 (m, 0.8H), 4.22 (q, 7.1 Hz, 2H), 4.46 (m,
1H), 4.55 (bd, J ) 6.7 Hz, 1H), 4.64 (bd, J ) 6.7 Hz, 1H), 5.06
(bs, 2H), 5.64 (bd, J ) 8 Hz, 0.2H), 5.8 (bd, J ) 7.4 Hz, 0.8H),
6.54 (dt, J ) 1.4, 7.4 Hz, 0.2H), 7.21 (bt, J ) 7.2 Hz, 0.8H),
7.33 (bs, 5H); 13C NMR (CDCl3, 75 MHz) (Z isomer) 14.2, 20.3,
27.9, 35.6, 38.2, 55.1, 55.3, 61.6, 66.9, 71.7, 82.6, 94.6, 128.1,
3.56. Found: C, 57.88; H, 5.94; N, 3.74. [R] ) -41.8 (c )
D
0.77, CHCl3).
Ack n ow led gm en t. We thank the CNRS for finan-
cial support and MENRT for a grant (X.M.)
(23) Liu, L.; Tanke, R. S.; Miller, M. J . J . Org. Chem. 1986, 51, 5332.
J O034195F
5350 J . Org. Chem., Vol. 68, No. 13, 2003