3714 Journal of Medicinal Chemistry, 2010, Vol. 53, No. 9
Singh and Bhardwaj
KSCN gave 3b in 89% yield as a colorless viscous oil. UV (EtOH):
λ
C-4), 73.9 (þve, CH), 112.3 (ab, CtN), 123.5 (þve, ArCH), 126.4
(þve, ArCH), 126.9 (þve, ArCH), 127.8 (þve, ArCH), 127.9 (þve,
ArCH), 132.4 (ab, ArC), 139.5 (ab, ArC), 146.1 (ab, ArC). FAB-
MS m/z 359 [Mþ] (73%), 361 [Mþ] (23%). Anal. (C19H18ClNO2S)
C, H, S, N.
max (ε) 217 (8020). IR (CHCl3, cm-1): 3465 (OH) 2156 (CN). 1H
NMR (300 MHz, CDCl3): δ 1.86-2.17 (m, 4H, 2H of C-3 þ 2H of
C-5), 2.18 (br s, 1H, OH), 3.07-3.24 (m, 2H, CH2), 4.36-4.41 (m,
1H, CH), 5.0 (dd, J1 = 8.4 Hz, J2 = 3.9 Hz, 1H, CH), 7.21-7.47
(m, 10H, ArH). 13C NMR (normal/DEPT-135, CDCl3): δ 39.3
(-ve, CH2), 41.9 (-ve, CH2), 45.5 (-ve, CH2), 71.6 (ab, C-4), 72.0
(þve, CH), 75.1 (þve, CH), 113.1 (ab, CtN), 124.2 (þve, ArCH),
125.6 (þve, ArCH), 127.5 (þve, ArCH), 128.3 (þve, ArCH), 128.5
(þve, ArCH), 141.6 (ab, ArC), 146.9 (ab, ArC). FAB-MS m/z 325
[Mþ]. Anal. (C19H19NO2S) C, H, S, N.
(2R*,4R*,6S*)-2-(4-Bromophenyl)-6-((ethylthio)methyl)tetra-
hydro-4-phenyl-2H-pyran-4-ol (3g). By use of procedure D, the
reaction of 15 with ethanthiol gave 3g in 92% yield as a colorless
viscous oil. UV (EtOH): λmax (ε) 219 (14200). IR (CHCl3, cm-1):
3462 (OH). 1H NMR (300 MHz, CDCl3): δ 1.25 (t, J = 7.8 Hz,
3H, CH3), 1.90-2.08 (m, 4H, 2H of C-3 þ 2H of C-5), 2.59-2.64
(m, 2H, S-CH2), 2.70-2.86 (m, 3H, 2H of CH2S, 1H of OH),
4.23-4.27 (m, 1H, CH), 5.01 (dd, J1 = 8.2 Hz, J2 = 3.9 Hz, 1H,
CH), 7.22-7.50 (m, 9H, ArH). 13C NMR (normal/DEPT-135,
CDCl3): δ 14.8 (þve, CH3), 27.1 (-ve, S-CH2), 37.1 (-ve,
CH2-S), 42.9 (-ve, CH2), 46.1 (-ve, CH2), 72.5 (ab, C-4),
73.6 (þve, CH), 75.1 (þve, CH), 119.8 (ab, ArC), 124.3 (þve,
ArCH), 124.5 (þve, ArCH), 124.8 (þve, ArCH), 125.8 (þve,
ArCH), 126.8 (þve, ArCH), 127.3 (þve, ArCH), 128.3 (þve,
ArCH), 128.5 (þve, ArCH), 142.5(ab, ArC), 147.7 (ab, ArC).
FAB-MS m/z 406 [Mþ] (96%), 408 [Mþ] (98%). Anal.
(C20H23BrO2S) C, H, S.
(2R*,4R*,6S*)-2-(4-Bromophenyl)tetrahydro-4-phenyl-6-(thiocy-
anatomethyl)-2H-pyran-4-ol (3h). By use of procedure D, the reac-
tion of 15 with KSCN gave 3h in 90% yield as a colorless viscous oil.
UV (EtOH): λmax (ε) 218 (14400). IR (CHCl3, cm-1): 3489 (OH)
2158 (CN). 1H NMR (300 MHz, CDCl3): δ 1.81-1.98 (m, 4H, 2H
of C-3 þ 2H of C-5), 3.02-3.19 (m, 2H, CH2), 4.30-4.36 (m, 1H,
CH), 4.95 (dd, J1 = 10.8 Hz, J2 = 3 Hz, 1H, CH), 7.17-7.41 (m,
9H, ArH). 13C NMR (normal/DEPT-135, CDCl3): δ 40.1 (-ve,
CH2), 42.7 (-ve, CH2), 46.3 (-ve, CH2), 72.5 (þve, CH), 72.8 (ab,
C-4), 75.3 (þve, CH), 113.7 (ab, CtN), 121.1 (ab, ArC), 124.9
(þve, ArCH), 127.8 (þve, ArCH), 128.4 (þve, ArCH), 129.2 (þve,
ArCH), 129.4 (þve, ArCH), 133.8 (þve, ArCH), 140.9 (ab, ArC),
147.5 (ab, ArC). FAB-MS m/z 403 [Mþ] (97%), 405 [Mþ] (100%).
Anal. (C19H18BrNO2S) C, H, S, N.
(2R*,3S*,4R*,6S*)-6-((Ethylthio)methyl)tetrahydro-2,3,4-tri-
phenyl-2H-pyran-4-ol (4a). By use of procedure D, the reaction of
24a with ethanthiol gave 4a in 95% yield as a colorless viscous oil.
UV (EtOH): λmax (ε) 219 (13890). IR (CHCl3, cm-1): 3467 (OH).
1H NMR (300 MHz, CDCl3): δ 1.10 (t, J = 7.5 Hz, 3H, CH3),
1.92-2.13 (m, 3H, 2H of C-5 þ 1H of OH), 2.41-2.46 (m, 2H,
S-CH2), 2.56-2.58 (m, 1H, CH2S) 2.67-2.74 (m, 1H, CH2S), 3.11
(d, J =9.9Hz, 1H, CH), 4.25-4.34 (m, 1H, CH), 5.12 (d, J =10.5
Hz, 1H, CH), 6.78-6.99 (m, 5H, ArH), 7.01-7.11 (m, 10H, ArH).
13C NMR (normal/DEPT-135, CDCl3): δ 14.8 (þve, CH3), 27.1
(-ve, S-CH2), 36.9 (-ve, CH2-S), 44.3 (-ve, CH), 58.1 (þve,
CH), 73.6 (þve, CH), 75.1 (ab, C-4), 78.9 (þve, CH), 124.5 (þve,
ArCH), 126.7 (þve, ArCH), 126.8 (þve, ArCH), 127.8 (þve,
ArCH), 128.0 (þve, ArCH), 128.9 (þve, ArCH), 129.8 (þve,
ArCH), 132.9 (þve, ArCH), 136.1 (ab, ArC), 139.3 (ab, ArC).
FAB-MS m/z 404 [Mþ]. Anal. (C26H28O2S) C, H, S.
(2R*,3S*,4R*,6S*)-Tetrahydro-2,3,4-triphenyl-6-(thiocya-
natomethyl)-2H-pyran-4-ol (4b). By use of procedure D, the
reaction of 24a with KSCN gave 4b in 92% yield as a colorless
viscous oil. UV (EtOH): λmax (ε) 221 (17840). IR (CHCl3, cm-1):
3454 (OH) 2157 (CN). 1H NMR (300 MHz, CDCl3): δ 2.03-2.39
(m, 3H, 2H of C-5 þ OH), 3.18 (d, J = 11.4 Hz, 1H, CH),
3.22-3.33 (m, 2H, CH2), 4.62-4.66 (m, 1H, CH), 5.32 (d, J =
10.8 Hz, 1H, CH), 6.90-6.97 (m, 3H, ArH), 7.00-7.28 (m, 12H,
ArH). 13C NMR(normal/DEPT-135, CDCl3): δ 39.0(-ve, CH2),
43.5 (-ve, C-5), 57.7 (þve, CH), 71.8 (þve, CH), 74.9 (ab, C-4),
79.1 (þve, CH), 112.7(ab, CtN), 124.4(þve, ArCH), 124.5 (þve,
ArCH), 126.7(þve, ArCH), 126.9 (þve, ArCH), 127.8 (þve,
ArCH), 128.0 (þve, ArCH), 128.2 (þve, ArCH), 129.7 (þve,
ArCH), 138.5 (þve, ArCH), 138.7 (ab, ArC). 139.1 (ab, ArC),
FAB-MS m/z 401 [Mþ]. Anal. (C25H23NO2S) C, H, S, N.
(2R*,3S*,4R*,6S*)-6-((Ethylthio)methyl)-2-(4-fluorophenyl)-
tetrahydro-3,4-diphenyl-2H-pyran-4-ol (4c). By use of procedure
D, the reaction of 24b with ethanthiol gave 4c in 94% yield as a
(2S*,4R*,6R*)-2-((Ethylthio)methyl)-6-(4-fluorophenyl)tetrahydro-
4-phenyl-2H-pyran-4-ol (3c). By use of procedure D, the reaction
of 13 with ethanthiol gave 3c in 92% yield as a colorless viscous oil.
UV (EtOH): λmax (ε) 217 (9930). IR (CHCl3, cm-1): 3433 (OH).
1H NMR (300 MHz, CDCl3): δ 1.24 (t, J = 7.8 Hz, 3H, CH3),
1.83-1.96 (m, 4H, 2H of C-3 þ 2H of C-5), 2.03-2.67 (m, 2H,
S-CH2), 2.77-2.83 (m, 3H, 2H of CH2S, 1H of OH), 4.19-4.22
(m, 1H, CH), 4.94 (dd, J1 = 8.4 Hz, J2 = 3.9 Hz, 1H, CH),
6.89-6.99 (m, 3H, ArH), 7.20-7.46 (m, 6H, ArH). 13C NMR
(normal/DEPT-135, CDCl3): δ 14.8 (þve, CH3), 26.9 (-ve, S-
CH2), 36.9 (-ve, CH2-S), 42.7 (-ve, CH2), 45.9 (-ve, CH2), 72.3
(ab, C-4), 73.6 (þve, CH), 74.5 (þve, CH), 115.0 (þve, JC-F
=
21.6 Hz, ortho to C-F, ArCH), 124.3 (þve, ArCH), 125.2 (þve,
ArCH), 126.7 (þve, ArCH), 126.8 (þve, JC-F = 13.6 Hz, meta to
C-F, ArCH), 127.2 (þve, ArCH), 127.4 (þve, ArCH),128.2
(þve, ArCH), 128.6 (þve, ArCH), 136.3 (ab, JC-F = 3 Hz, para
to C-F, ArC), 145.5 (ab, ArC), 162.2 (ab, JC-F = 243.2 Hz,
ArC-F). FAB-MS m/z 346 [Mþ]. Anal. (C20H23FO2S) C, H, S.
(2R*,4R*,6S*)-2-(4-Fluorophenyl)tetrahydro-4-phenyl-6-(thiocy-
anatomethyl)-2H-pyran-4-ol (3d). By use of procedure D, the reac-
tion of 13 with KSCN gave 3d in 90% yield as a colorless viscous oil.
UV (EtOH): λmax (ε) 219 (6820). IR (CHCl3, cm-1): 3434(OH),
2164 (CN). 1H NMR (300 MHz, CDCl3): δ 1.72-1.93 (m, 4H, 2H
of C-3 þ 2H of C-5), 2.30 (br s, 1H, OH), 2.98-3.12 (m, 2H, CH2),
4.26-4.29 (m, 1H, CH), 4.91 (dd, J1 = 8.4 Hz, J2 = 3.9 Hz, 1H,
CH), 6.86-6.94 (m, 2H, ArH), 7.11-7.37 (m, 7H, ArH). 13CNMR
(normal/DEPT-135, CDCl3): δ 38.6 (-ve, CH2), 41.3 (-ve, CH2),
44.9 (-ve, CH2), 71.1 (ab, C-4), 71.4 (þve, CH), 73.9 (þve, CH),
112.4 (ab, CtN), 115.2 (þve, JC-F = 21.6 Hz, ortho to C-F,
ArCH), 123.6 (þve, ArCH), 126.6 (þve, ArCH), 126.8 (þve,
ArCH), 127.3 (þve, JC-F = 8 Hz, meta to F, ArCH), 127.9
(þve, ArCH), 136.8 (þve, ArCH), 142.2 (ab, JC-F = 4.2 Hz, para
to F, ArC), 147.3 (ab, ArC), 162.2 (ab, JC-F = 243.2 Hz, ArC-F).
FAB-MS m/z 343 [Mþ]. Anal. (C19H18FNO2S) C, H, S, N.
(2R*,4R*,6S*)-2-(4-Chlorophenyl)-6-((ethylthio)methyl)tetrahy-
dro-4-phenyl-2H-pyran-4-ol (3e). By use of procedure D, the reac-
tion of 14 with ethanthiol gave 3e in 93% yield as a colorless viscous
oil. UV (EtOH): λmax (ε) 220 (12580). IR (CHCl3, cm-1): 3485
1
(OH). H NMR (300 MHz, CDCl3): δ 1.26 (t, J = 7.5 Hz, 3H,
CH3), 1.88-2.06 (m, 4H, 2H of C-3 þ 2H of C-5), 2.60-2.67 (m,
2H, S-CH2), 2.71-2.89 (m, 3H, 2H of CH2S, 1H of OH),
4.22-4.29 (m, 1H, CH), 5.01 (dd, J1 = 8.3 Hz, J2 = 3.9 Hz, 1H,
CH), 7.22-7.51 (m, 9H, ArH). 13C NMR (normal/DEPT-135,
CDCl3): δ 14.8 (þve, CH3), 27.1 (-ve, S-CH2), 37.1 (-ve,
CH2-S), 42.9 (-ve, CH2), 46.1 (-ve, CH2), 72.5 (ab, C-4), 73.7
(þve, CH), 75.2 (þve, CH), 124.3 (þve, ArCH), 125.8 (þve,
ArCH), 127.3 (þve, ArCH), 128.5 (þve, ArCH), 128.9 (þve,
ArCH), 130.9 (þve, ArCH), 132.3 (ab, ArC), 142.5 (ab, ArC),
147.7 (ab, ArC). FAB-MS m/z 362 [Mþ] (73%), 364 [Mþ] (23%).
Anal. (C20H23ClO2S) C, H, S.
(2R*,4R*,6S*)-2-(4-Chlorophenyl)tetrahydro-4-phenyl-6-(thiocy-
anatomethyl)-2H-pyran-4-ol (3f). By use of procedure D, the reac-
tion of 14 with KSCN gave 3f in 92% yield as a colorless viscous oil.
UV (EtOH): λmax (ε) 221 (15700). IR (CHCl3, cm-1): 3457 (OH)
2170 (CN). 1H NMR (300 MHz, CDCl3): δ 1.97-2.03 (m, 4H, 2H
of C-3 þ 2H of C-5), 3.17-3.34 (m, 2H, CH2), 4.42-4.51 (m, 1H,
1H of CH), 5.07 (dd, J1 = 9.8 Hz, J2 = 3 Hz, 1H, CH), 7.31-7.56
(m, 9H, ArH). 13C NMR (normal/DEPT-135, CDCl3):δ38.6 (-ve,
CH2), 41.3 (-ve, CH2), 44.9 (-ve, CH2), 71.1 (þve, CH), 71.4 (ab,