3268
R. A. Davis et al. / Tetrahedron 58 72002) 3263±3269
*190 mg, 2.32 mmol). The mixture was heated at re¯ux for
2 h then allowed to cool to rt. The precipitate was collected,
washed with chilled H2O *3£5 mL) and dried under vacuum
overnight to yield the corresponding thiohydantoin analog.
248 *1 10,000), 298 *1 6000), 370 nm *1 26,000);IR nmax
*NaCl) 1747, 1726, 1711, 1657, 1586, 1511, 1493, 1452,
1427, 1366, 1293, 1270, 1219, 1193, 1165, 1124, 1025,
1
1011, 948, 918, 897, 831, 682, 616, 540 cm21; H NMR
*400 MHz, DMSO-d6) d 2.26 *3H, s, 10-OAc), 3.85 *3H,
s, 9-OMe), 6.49 *1H, s, H-6), 7.12 *1H, d, J8.4 Hz, H-11),
7.34 *1H, dd, J8.4, 2.0 Hz, H-12), 7.36 *1H, d, J2.0 Hz,
4.4.1. Thiohydantoin 12a [.5Z)-5-.3-methoxy-4-hydroxy-
benzylidene)-2-thioxoimidazolidin-4-one].
Compound
²
²
12a was puri®ed by fractional recrystallization using
MeOH/H2O *3:1). After ®ltration and drying under vacuum
the thiohydantoin 12a was obtained as brown needles
*367 mg, 63% yield);mp 234±236 8C;UV *MeOH) lmax
258 *1 11,000), 300 *1 7000), 392 nm *1 31,000);IR nmax
*NaCl) 3600±3000, 1710, 1638, 1588, 1506, 1374, 1349,
1290, 1268, 1213, 1183, 1128, 1097, 1029, 971, 946, 894,
H-8), 12.21 *1H, br s, 1-NH), 12.39 *1H, br s, 3-NH); 13
C
NMR *100 MHz, DMSO-d6) d 20.4 *10-OAc), 56.1
*9-OMe), 111.1 *C-6), 114.3 *C-8), 122.9 *C-12), 123.2
*C-11), 127.7 *C-5), 131.2 *C-7), 140.0 *C-10), 151.0
*C-9), 165.8 *C-4), 168.4 *10-OAc), 179.3 *C-2);LREIMS
*70 eV) m/z *rel. int.) 43 *10), 163 *40), 250 *100), 292 *15);
HREIMS *70 eV) m/z 292.05075 *C13H12N2O4S requires
292.05178).
1
865, 840, 800, 753, 725, 672, 633, 613 cm21; H NMR
*400 MHz, DMSO-d6) d 3.84 *3H, s, 9-OMe), 6.42 *1H, s,
H-6), 6.80 *1H, d, J8.8 Hz, H-11), 7.23 *1H, d, J2.0 Hz,
H-8), 7.24 *1H, dd, J8.8, 2.0 Hz, H-12), 9.63 *1H, br s,
4.4.6. Thiohydantoin 14b [.5E)-5-.3-methoxy-4-acetoxy-
benzylidene)-2-thioxoimidazolidin-4-one]. 1H NMR
*400 MHz, DMSO-d6) d 2.25 *3H, s, 10-OAc), 3.79 *3H,
s, 9-OMe), 6.56 *1H, s, H-6), 7.08 *1H, d, J8.4 Hz, H-11),
7.48 *1H, dd, J8.4, 2.0 Hz, H-12), 8.10 *1H, d, J2.0 Hz,
²
²
10-OH), 12.05 *1H, br s, 1-NH), 12.25 *1H, br s, 3-NH);
13C NMR *100 MHz, DMSO-d6) d 55.9 *9-OMe), 113.3
*C-6), 114.0 *C-8), 115.8 *C-11), 123.8 *C-7), 124.8
*C-12), 125.3 *C-5), 147.8 *C-9), 148.6 *C-10), 165.9
*C-4), 178.3 *C-2);LREIMS *70 eV) m/z *rel. int.) 163
²
²
H-8), 12.08 *1H, br s, 1-NH), 12.27 *1H, br s, 3-NH).
4.4.7. Thiohydantoin 15a [.5Z)-5-.3-methoxy-4-pivaloyl-
oxybenzylidene)-2-thioxoimidazolidin-4-one].
*100), 250 *100);HREIMS *70 eV)
*C11H10N2O3S requires 250.04121).
m/z 250.04013
Pale
yellow solid *504 mg, 65% yield);mp 215±217 8C;UV
*MeOH) lmax 248 *1 12,000), 296 *1 8000), 370 nm *1
32,000);IR nmax *NaCl) 1732, 1653, 1592, 1508, 1489,
1452, 1362, 1318, 1271, 1237, 1180, 1126, 1030, 963,
4.4.2. Thiohydantoin 12b [.5E)-5-.3-methoxy-4-hydroxy-
benzylidene)-2-thioxoimidazolidin-4-one]. 1H NMR
*400 MHz, DMSO-d6) d 3.79 *3H, s, 9-OMe), 6.51 *1H, s,
H-6), 6.77 *1H, d, J8.4 Hz, H-11), 7.35 *1H, dd, J8.4,
2.0 Hz, H-12), 8.16 *1H, d, J2.0 Hz, H-8), 9.70 *1H, br s,
1
946, 894, 835, 754, 675, 633, 620, 590 cm21; H NMR
*500 MHz, DMSO-d6) d 1.29 *9H, s, 10-OPv), 3.83 *3H,
s, 9-OMe), 6.48 *1H, s, H-6), 7.09 *1H, d, J9.0 Hz, H-11),
7.36 *1H, dd, J9.0, 2.0 Hz, H-12), 7.37 *1H, d, J2.0 Hz,
²
²
10-OH), 11.92 *1H, br s, 1-NH), 12.13 *1H, br s, 3-NH).
²
²
H-8), 12.22 *1H, br s, 1-NH), 12.38 *1H, br s, 3-NH); 13
C
4.4.3. Thiohydantoin 13a [.5Z)-5-.3,4-dimethoxybenzyl-
idene)-2-thioxoimidazolidin-4-one].
NMR *125 MHz, DMSO-d6) d 26.8 *10-OPv), 38.6
*10-OPv), 56.2 *9-OMe), 111.2 *C-6), 114.4 *C-8), 123.0
*2C, C-11, C-12), 127.6 *C-5), 131.1 *C-7), 140.5 *C-10),
151.0 *C-9), 165.8 *C-4), 175.7 *10-OPv), 179.3 *C-2);
LREIMS *70 eV) m/z *rel. int.) 57 *100), 91 *25), 163
*30), 218 *30), 250 *50), 334 *30);HREIMS *70 eV) m/z
334.09707 *C16H18N2O4S requires 334.09873).
Yellow
solid
*504 mg, 82% yield);mp 231±233 8C;UV *MeOH) lmax
256 *1 12,000), 300 *1 7000), 388 nm *1 32,000);IR nmax
*NaCl) 1718, 1647, 1593, 1512, 1490, 1362, 1331, 1273,
1253, 1229, 1175, 1143, 1084, 1019, 946, 874, 807, 759,
668, 548 cm21; 1H NMR *400 MHz, DMSO-d6) d 3.80 *3H,
s, 10-OMe), 3.83 *3H, s, 9-OMe), 6.45 *1H, s, H-6), 6.98
*1H, d, J8.0 Hz, H-11), 7.24 *1H, d, J2.0 Hz, H-8), 7.35
*1H, dd, J8.0, 2.0 Hz, H-12), 12.12 *1H, br s, 1-NH),
12.29 *1H, br s, 3-NH); 13C NMR *100 MHz, DMSO-d6)
d 55.6 *10-OMe), 55.8 *9-OMe), 111.7 *C-11), 112.7 *C-6),
113.3 *C-8), 124.4 *C-12), 125.0 *C-7), 125.8 *C-5), 148.8
*C-9), 150.2 *C-10), 165.8 *C-4), 178.6 *C-2);LREIMS
*70 eV) m/z *rel. int.) 69 *100), 131 *30), 162 *20), 264
4.4.8. Thiohydantoin 15b [.5E)-5-.3-methoxy-4-pivaloyl-
oxybenzylidene)-2-thioxoimidazolidin-4-one]. 1H NMR
*500 MHz, DMSO-d6) d 1.29 *9H, s, 10-OPv), 3.78 *3H,
s, 9-OMe), 6.56 *1H, s, H-6), 7.06 *1H, d, J8.0 Hz, H-11),
7.48 *1H, dd, J8.0, 2.0 Hz, H-12), 8.11 *1H, d, J2.0 Hz,
²
²
H-8), 12.08 *1H, br s, 1-NH), 12.27 *1H, br s, 3-NH).
*95);HREIMS *70 eV)
requires 264.05686).
m/z 264.05535 *C12H12N2O3S
4.5. Synthesis of polyandrocarpamine A .1)
4.4.4. Thiohydantoin 13b [.5E)-5-.3,4-dimethoxybenzyl-
idene)-2-thioxoimidazolidin-4-one]. H NMR *400 MHz,
70% TBHP *385 mL, 3.0 mmol) and 30% aqueous NH4OH
*1 mL) were added to a solution of the pivaloylated thio-
hydantoin 15a *66.8 mg, 0.2 mmol) in MeOH *3 mL) and
the mixture was stirred for 72 h at rt. The solvents were
removed under reduced pressure and the resulting residue
chromatographed on a C18 packed SPE cartridge using 20%
stepwise elutions from 20% MeOH/80% H2O to 100%
MeOH. The 40% MeOH/60% H2O fraction was further
puri®ed by HPLC using a Phenomenex Luna C18*2) semi-
preparative column with a linear gradient from 100% H2O
to 100% MeOH in 20 min at a ¯owrate of 4 mL/min. This
yielded a pure 2-aminoimidazolone compound *32 mg, 68%
1
²
²
DMSO-d6) d 3.78 *3H, s, 10-OMe), 3.79 *3H, s,
9-OMe), 6.54 *1H, s, H-6), 6.97 *1H, d, J8.8 Hz, H-11),
7.46 *1H, dd, J8.8, 2.0 Hz, H-12), 8.14 *1H, d, J2.0 Hz,
²
²
H-8), 11.97 *1H, br s, 1-NH), 12.17 *1H, br s, 3-NH).
4.4.5. Thiohydantoin 14a [.5Z)-5-.3-methoxy-4-acetoxy-
benzylidene)-2-thioxoimidazolidin-4-one]. Yellow solid
*587 mg, 87% yield);mp 252±253 8C;UV *MeOH) lmax
²
Interchangeable signals.