4698 J ournal of Medicinal Chemistry, 2000, Vol. 43, No. 24
Pragnacharyulu et al.
(2S,3S)-2-(Ben zyloxy)-8-ph en yloctan -3-ol (9h ). This com-
exchangeable), 6.90-7.35 (m, 10H), 7.90 (s, 1H), 8.30 (s, 1H).
Anal. (C24H27N5O) C, H, N.
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(ben zyloxy)-8-p h en yl-
octa n e (10h ). This compound was prepared from 9h in 28%
overall yield as a white solid: [R]D25 +19.78° (c 0.665, CH2Cl2).
Anal. (C24H27N5O) C, H, N.
Deben zyla tion of Com p ou n d s 10 (P r oced u r e D). A
mixture of the adenine derivative 10 (1 equiv), Pd(OH)2/C
(equal in weight to the starting material) in ethanol (20 mL)
and cyclohexene (10 mL) was stirred at reflux overnight then
allowed to cool to room temperature. The mixture was then
filtered and the solution was concentrated under reduced
pressure. The residue was placed on a silica gel column and
eluted with EtOAc (50 mL) and then with EtOAc:MeOH (10:
1) to yield the desired product.
(2S,3R)-3-(6-Am in opu r in -9-yl)-4-(2-pr opylph en yl)bu tan -
2-ol (11a ). This compound was prepared from 10a in 91%
yield: mp 181-182 °C; [R]D25 +377.0° (c 0.29, EtOH); 1H NMR
δ 0.80 (t, J ) 9 Hz, 3H), 1.15-1.60 (m, 5H), 2.30 (t, J ) 9 Hz,
2H), 3.10-3.40 (m, 2H), 3.75 (bs, 2H D2O exchangeable), 7.25
(s, 1H), 8.10 (s, 1H). Anal. (C19H23N5O) C, H.
pound was prepared from 4-phenyl-1-chlorobutane using
25
procedure B in 80% yield as a clear gum: [R]D +19.78° (c
1.39, CH2Cl2). Anal. (C21H29O2) C, H.
P r ep a r a tion of Com p ou n d 10 (P r oced u r e C). To a
solution of the alcohol 9 (1 equiv), TPP (2 equiv), and
6-chloropurine (2 equiv) in dry THF was slowly added DIAD
(2 equiv). The resulting mixture was stirred at reflux, under
nitrogen, overnight. After cooling and concentrating, the
residue was applied to a short silica column and eluted with
Et2O. The combined Et2O fractions were concentrated to about
100 mL and washed with brine (2 × 20 mL) and distilled water
(20 mL). The organic layer was then dried and concentrated
to give the crude product. This material was partially purified
by silica gel chromatography [hexanes-EtOAc (10:1f 1:10)]
and was placed in liquid ammonia and heated in a bomb at
90 °C overnight. Cooling, evaporation of the ammonia, dilution
with CH2Cl2 (50 mL), washing with distilled water (3 × 5 mL),
and evaporation of the organic layer gave a residue which was
chromatographed on a silica column (hexanes-EtOAc) to
obtain the desired product.
(2S,3R)-3-(6-Am in op u r in -9-yl)-4-(3-eth ylp h en yl)bu ta n -
2-ol (11b). This compound was prepared from 10b in 90%
yield: mp 157-158 °C; [R]D25 +143.0° (c 1.115, EtOH); 1H NMR
δ 1.05 (t, J ) 8 Hz, 3H), 1.35 (d, J ) 6 Hz, 3H), 2.45 (q, J ) 8
Hz, 2H), 3.20 (d, J ) 6 Hz, 3H), 4.20-4.60 (m, 2H), 4.95 (bs,
2H, 1H D2O exchangeable), 6.50-7.20 (m, 4H, 2H D2O
exchangeable), 7.50 (s, 1H), 8.20 (s, 1H). Anal. (C17H21N5O) C,
H, N.
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(ben zyloxy)-4-(2-p r op -
2-en ylp h en yl)bu ta n e (10a ). This compound was prepared
25
from alcohol 9a in 9% overall yield: [R]D +120.9° (c 0.67,
CH2Cl2); 1H NMR δ 1.20 (d, J ) 6 Hz, 3H), 1.50-1.80 (m, 3H),
2.30-2.60 (m, 3H), 2.80-3.50 (m, 1H), 4.55 (AB q center, ∆AB
) 18 Hz, J AB ) 12 Hz, 2H), 5.35-6.40 (m, 2H, 2H D2O
exchangeable), 6.80-7.40 (m, 9H), 8.0 (s, 1H), 8.30 (s, 1H).
Anal. (C25H27N5O) C, H, N.
(2S,3R)-3-(6-Am in opu r in -9-yl)-4-(4-m eth ylph en yl)bu tan -
2-ol (11c). This compound was prepared in 65% yield from
10c: mp 156-158 °C; [R]D25 +247.7° (c 0.17, CHCl3); 1H NMR
δ 1.33 (d, J ) 6 Hz, 3H), 2.16 (s, 3H), 3.16 (d, J ) 7.5 Hz, 2H),
4.05-4.50 (m, 3H), 5.80 (bs, 2H), 6.40-6.90 (dd, J AB ) 9 Hz,
4H), 7.98 (s, 1H), 8.16 (s, 1H). Anal. (C16H19N5O) C, H, N.
(2S,3R)-3-(6-Am in op u r in -9-yl)-5-(3-m eth ylp h en yl)p en -
ta n -2-ol (11d ). This compound was prepared from 10d in 62%
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(b en zyloxy)-4-(3-et h -
en ylp h en yl)bu ta n e (10b). This product was obtained from
25
9b in 11.4% yield as a white solid: mp 116-118 °C; [R]D
1
+142.8° (c 0.83, CH2Cl2); H NMR δ 1.35 (d, J ) 6 Hz, 3H),
3.30-3.70 (m, 2H), 4.0-4.20 (m, 1H), 4.55 (AB q center, ∆AB
) 24 Hz, J AB ) 12 Hz, 2H), 4.60-4.90 (m, 1H), 5.10 (d, J ) 10
Hz, 1H), 5.50 (d, J ) 18 Hz, 1H), 6.50 (dd, J ) 18 Hz, 10 Hz,
1H), 6.70-7.20 (m, 4H, 2H D2O exchangeable), 7.30-7.50 (m,
5H), 7.26 (s, 5H), 7.80 (s, 1H), 8.30 (s, 1H). Anal. (C24H25N5O)
C, H, N.
1
yield: mp 146-148 °C; [R]D+55.9° (c 0.315, CHCl3); H NMR
δ 1.21 (d, J ) 6 Hz, 3H), 2.28 (s, 3H), 2.33-2.68 (m, 4H), 4.03-
4.46 (m, 2H), 4.95 (bs, 1H), 6.50 (bs, 2H), 6.75-7.09 (m, 4H),
7.76(s, 1H), 8.26 (s, 1H). Anal. (C17H21N5O) C, H, N.
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(ben zyloxy)-4-(4-m eth -
ylp h en yl)bu ta n e (10c). This compound was prepared in
14.5% yield from 9C following procedure C: mp 144-146 °C;
(2S,3R)-3-(6-Am in opu r in -9-yl)-6-ph en ylh exan e-2-ol (11e).
This compound was prepared from 10e in 98% yield: mp 153-
25
1
[R]D +106.4° (c 1.91, CH2Cl2); H NMR δ 1.20 (d, J ) 6 Hz,
3H), 2.16 (s, 3H), 3.20-3.43 (m, 2H), 3.88-4.76 (m, 4H), 5.81
(bs, 2H), 6.83 (s, 4H), 7.26 (s, 5H), 7.68 (s, 1H), 8.23 (s, 1H).
Anal. (C23H25N5O) C, H, N.
154 °C; [R]D +51.0° (c 0.36, EtOH); 1H NMR δ 1.15 (d, J ) 6
25
Hz, 3H), 1.20-1.60 (m, 2H), 1.70-2.20 (m, 2H), 2.40-2.70 (m,
2H), 3.95-4.50 (m, 2H D2O exchangeable), 6.60-7.25 (m, 7H,
2H D2O exchangeable), 7.80 (s, 1H), 8.20 (s, 1H). Anal.
(C17H21N5O) C, H, N.
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(ben zyloxy)-5-(3-m eth -
ylp h en yl)p en ta n e (10d ). This compound was prepared from
alcohol 9d in 30% overall yield: mp 155-157 °C; [R]D25 +52.5°
(2S,3R)-3-(6-Am in opu r in -9-yl)-6-(2-m eth ylph en yl)h exan -
2-ol (11f). This compound was prepared from 10f in 71% yield
1
(c 0.415, CHCl3); H NMR δ 1.20 (d, J ) 6 Hz, 3H), 2.25 (s,
25
as a white solid: mp 153-155 °C; [R]D +33.6° (c 1.155,
3H), 2.30-2.48 (m, 4H), 3.70-4.03 (m, 1H), 4.18-4.68 (m, 3H),
5.93 (bs, 2H), 6.66-7.40 (m, 9H), 7.91 (s, 1H), 8.33 (s, 1H).
Anal. (C24H27N5O) C, H, N.
EtOH); 1H NMR δ 1.15 (d, J ) 6 Hz, 3H), 1.20-1.55 (m, 2H),
1.75-2.25 (m, 2H), 2.15 (s, 3H), 2.40-2.70 (m, 2H), 3.95-4.50
(m, 2H, D2O exchangeable), 6.65-7.25 (m, 6H, 2H D2O
exchangeable), 7.80 (s, 1H), 8.20 (s, 1H). Anal. (C18H23N5O) C,
H, N.
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(ben zyloxy)-6-p h en yl-
h exa n e (10e). This compound was prepared from 9e in 13%
25
overall yield as a white solid: mp 139-140 °C; [R]D +80.7°
(2S,3R)-3-(6-Am in op u r in -9-yl)-7-h ep ta n -2-ol (11 g). This
(c 1.97, CH2Cl2); 1H NMR δ 1.20 (d, J ) 6 Hz, 3H), 1.30-1.70
(m, 2H), 1.95-2.30 (m, 2H), 2.60 (t, J ) 8 Hz, 2H), 3.70-3.95
(m, 1H), 4.40 (AB q center, ∆AB ) 24 Hz, J AB ) 12 Hz, 2H),
4.45-4.70 (m, 1H) 6.35 (m, 2H, 2H D2O exchangeable), 6.95-
7.35 (m, 10H), 7.90 (s, 1H), 8.30 (s, 1H). Anal. (C24H27N5O) C,
H, N.
compound was prepared from 10g in 92% yield: [R]D25 +37.4°
1
(c 0.39, EtOH); H NMR δ 0.90-1.70 (m, 7H), 1.70-2.10 (m,
2H), 2.10-2.50 (m, 2H), 3.94-4.40 (m, 2H), 4.80 (bs, 1H D2O
exchangeable), 6.60-7.20 (m, 7H, 2H D2O exchangeable), 7.75
(s, 1H), 8.10 (s, 1H). Anal. (C18H23N5O) C, H, N.
(2S,3R)-3-(6-Am in opu r in -9-yl)-8-ph en yloctan -2-ol (11h ).
25
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(ben zyloxy)-6-(2-m eth -
ylp h en yl)h exa n e (10f). This compound was prepared from
This compound was prepared from 10h in 89% yield: [R]D
1
+49.6° (c 0.365, EtOH); H NMR δ 0.85-1.65 (m, 9H), 1.65-
25
9f in 18% overall yield as a white solid: mp 141-142 °C; [R]D
+76.5° (c 0.23, CH2Cl2). Anal. (C25H29N5O) C, H, N.
2.05 (m, 2H), 2.05-2.5 (m, 2H), 3.95-4.45 (m, 2H), 4.80 (bs,
1H D2O exchangeable), 6.65-7.25 (m, 7H, 2H D2O exchange-
able), 7.75 (s, 1H), 8.10 (s, 1H). Anal. (C17H21N5O) C, H, N.
(2S,3S)-3-O-Ben zyl-1-O-n -bu tylbu ta n e-1,2,3-tr iol (12a ).
n-BuOH (3.1 mL, 33.71 mmol), NaOH (0.45 g, 11.24 mmol)
and water (0.45 mL) were mixed and refluxed for 30 min. To
this solution was added epoxide 3 (1 g, 5.62 mmol), and the
resulting solution was refluxed for 1 h. n-BuOH was removed,
and the residue was diluted with water (50 mL) and extracted
(2S,3R)-3-(6-Am in op u r in -9-yl)-2-(ben zyloxy)-7-p h en yl-
h ep ta n e (10g). This compound was prepared from 9g in 8.3%
25
overall yield as a white solid: mp 102-103 °C; [R]D +65.41°
1
(c 1.405, CH2Cl2); H NMR δ 0.90-1.30 (m, 2H), 1.10 (d, J )
6 Hz, 3H), 1.35-1.70 (m, 2H), 1.90-2.25 (m, 2H), 2.35-2.60
(m, 2H), 3.70-3.95 (m, 1H), 4.55 (AB q center, ∆AB ) 24 Hz,
J AB ) 12 Hz, 2H), 4.40-4.70 (m, 1H) 6.55 (bs, 2H, 2H D2O