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A. E. Wroblewski, W. Karolczak / Tetrahedron 59 (2003) 6075–6081
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4.1.8. Methyl (2R,3S)-3,4-O-cyclohexylidene-2,3,4-trihy-
droxy-3-O-(p-toluenesulfonyl)butanoate, (2R,3R)-17. In a
similar manner as described for (2R,3S)-10, from (2R,3R)-
16 (0.657 g, 2.81 mmol) and tosyl chloride (0.570 g,
3.00 mmol), (2R,3R)-17 (1.05 g, 96%) was obtained as a
colourless oil. [a]2D0¼þ6.4 (c¼1.6, methanol). IR (film):
n¼2936, 2862, 1757, 1371, 1096 cm21. 1H NMR (CDCl3):
d¼1.25–1.42 (2H, m), 1.45–1.57 (8H, m), 2.45 (3H, s),
3.64 (3H, s), 3.93 (1H, dAB, JAB¼9.0 Hz, J¼4.6 Hz), 4.00
(1H, dAB, JAB¼9.0 Hz, J¼6.0 Hz), 4.35 (1H, ddd, J¼6.1,
6.0, 4.6 Hz), 4.79 (1H, d, J¼6.1 Hz), 7.35 (2H, d,
J¼8.3 Hz), 7.80 (2H, d, J¼8.3 Hz). 13C NMR (CDCl3):
d¼21.98, 23.92, 24.10, 25.23, 34.78, 36.27, 52.84, 65.39,
74.48, 77.01, 111.37, 128.29, 129.88, 132.79, 145.45,
167.15. Anal. calcd for C18H24O7S (384.37): C, 56.24; H,
6.29. Found: C, 56.56; H, 6.57.
A solution of (2R,3S)-18 (0.700 g) in methanol (3 mL) was
stirred with anhydrous K2CO3 (0.291 g, 2.11 mmol) at room
temperature for 30 h. After addition of saturated NH4Cl, the
solution was concentrated in vacuo. Water (5 mL) was
added to the residue, the aqueous phase was then extracted
with CH2Cl2 (3£10 mL) and the organic extracts were dried
over MgSO4 and concentrated. The crude product was
chromatographed on a silica gel column with chloroform–
methanol (200:1, v/v) to give (2R,3R)-19 (0.240 g, 67%) as
a colourless oil. [a]2D0¼223.6 (c¼0.7, methanol). IR (film):
1
n¼2935, 2860, 1449, 1368, 1163, 1102 cm21. H NMR
(CDCl3): d¼1.30–1.45 (2H, m), 1.45–1.70 (8H, m), 2.68
(1H, dd, J¼5.1, 2.7 Hz), 2.79 (1H, dd, J¼5.1, 4.2 Hz), 3.03
(1H, ddd, J¼5.1, 4.2, 2.7 Hz), 3.84 (1H, dd, J¼8.0, 6.2 Hz),
3.98 (1H, ddd, J¼6.5, 6.2, 5.1 Hz), 4.09 (1H, dd, J¼8.0,
6.5 Hz). 13C NMR (CDCl3): d¼24.07, 24.22, 25.36, 35.28,
36.25, 44.12, 52.37, 65.77, 76.01, 110.69. Anal. calcd for
C10H16O3 (184.23): C, 65.19; H, 8.76. Found: C, 64.96; H,
8.80.
4.1.9. (2S,3S)-1,2-O-Isopropylidene-3-O-(p-toluenesul-
phonyl)butane-1,2,3,4-tetrol, (2S,3S)-11. A solution of
(2R,3S)-10 (1.376 g, 4.000 mmol) in THF–EtOH (1:2,
18 mL) containing anhydrous LiCl (0.504 g, 12.0 mmol)
was cooled to 258C and NaBH4 (0.444 g, 12.0 mmol) was
added at this temperature portionwise. The reaction mixture
was stirred at room temperature overnight, treated with
acetone (8 mL) and after 30 min diluted with chloroform.
Anhydrous MgSO4 (3 g) was added and the suspension was
vigorously stirred for 1 h and filtered through a layer of
Celite 535. Solvents were evaporated and the crude product
was chromatographed on a silica gel column with chloro-
form–methanol (50:1) to give (2S,3S)-11 (1.165 g, 93%) as
a colourless oil. [a]2D0¼þ9.9 (c¼1.1, methanol). IR (film):
n¼3452, 2993, 2931, 1355, 1178 cm21. 1H NMR (CDCl3):
d¼1.27 and 1.28 (6H, 2s), 2.17 (1H, brs), 2.45 (3H, s), 3.80
and 3.82 (2H, AB part of ABX, JAB¼12.9 Hz, J¼5.1,
4.3 Hz), 3.88 (1H, dAB, JAB¼9.0 Hz, J¼5.7 Hz), 4.01 (1H,
dAB, JAB¼9.0 Hz, J¼6.9 Hz), 4.31 (1H, ddd, J¼6.9, 5.7,
4.8 Hz), 4.57 (1H, ddd, J¼5.1, 4.8, 4.3 Hz), 7.33–7.37 and
7.82–7.86 (4H, m). 13C NMR (CDCl3): d¼21.72, 25.28,
26.09, 62.08, 65.35, 74.49, 81.68, 110.04, 128.08, 129.80,
133.29, 145.10. Anal. calcd for C14H20O6S (316.30): C,
53.07; H, 6.50. Found: C, 52.89; H, 6.49.
4.1.11. 9-[(20R,30S)-20,30,40-Trihydroxy-30,40-O-isopropyl-
idenebutyl]adenine, (20R,30S)-9. A mixture of the epoxide
(2S,3R)-12 (0.144 g, 1.00 mmol), adenine (0.135 g,
1.00 mmol), DMF (3 mL) and cesium carbonate (0.40 g,
1.2 mmol) was stirred at 1208C for 46 h. After cooling the
suspension was filtered and the subsequent solution was
concentrated in vacuo (0.1 mm Hg) and the residue was
coevaporated with toluene (3£3 mL). The crude product
was purified on a silica gel column with chloroform–
methanol (4:1, v/v) to give (20R,30S)-9 (0.223 g, 80%),
which was recrystallised from methanol–petroleum ether
(colourless needles). Mp 176–1788C. [a]2D0¼þ8.8 (c¼3.6,
methanol). IR (KBr): n¼3291, 2926, 1701, 1652, 1072,
1
669 cm21. H NMR (CD3OD): d¼1.33 and 1.42 (6H, 2s),
3.86 (1H, dt, J¼8.4, 3.0 Hz), 3.9–4.1 (3H, ABC system),
4.15 (1H, dd, JAB¼14.4 Hz, J¼8.4 Hz), 4.54 (1H, dd,
JAB¼14.4 Hz, J¼3.0 Hz), 8.11 (1H, s), 8.19 (1H, s). 13C
NMR (CD3OD): d¼26.34, 27.92, 49.13, 68.73, 72.74,
79.15, 111.71, 120.54, 144.44, 151.60, 154.26, 157.82.
Anal. calcd for C12H17O3N5 (279.29): C, 51.60; H, 6.14; N,
25.08. Found: C, 51.25; H, 6.38; N, 24.92.
4.1.10. (2R,3R)-1,2-O-Cyclohexylidene-3,4-epoxybutane-
1,2-diol, (2R,3R)-19. A solution of (2R,3R)-17 (0.836 g,
2.18 mmol) in THF–EtOH (1:2, 12 mL) containing anhy-
drous LiCl (0.273 g, 6.51 mmol) was cooled to 08C and
NaBH4 (0.240 g, 6.51 mmol) was added at this temperature
portionwise. The reaction mixture was stirred at room
temperature overnight, treated with acetone (2 mL) and
after 30 min diluted with chloroform (30 mL). Anhydrous
MgSO4 (2 g) was added and the suspension was vigorously
stirred for 1 h and filtered through a layer of Celite 535.
Solvents were evaporated to give crude (2R,3S)-18
(0.700 g) as a colourless very viscous oil of sufficient purity
to be used in the next step. IR (film): n¼3412, 2926, 2854,
4.1.12. 9-[(20R,30R)-30,40-O-Cyclohexylidene-20,30,40-tri-
hydroxybutyl]adenine, (20R,30R)-20. In a similar manner
as described for (20R,30S)-9, from (2R,3R)-19 (0.25 g,
1.3 mmol), adenine (0.20 g, 1.5 mmol), DMF (5 mL) and
Cs2CO3 (0.65 g, 2.0 mmol), (20R,3R0)-20 (0.246 g, 55%) was
obtained as a white powder. Mp 185–1868C. [a]2D0¼þ25.9
(c¼0.7, methanol). IR (KBr): n¼3338, 3199, 2931, 2544,
1619, 1574, 1479, 1340, 1232, 1094 cm21 1H NMR
.
(CD3OD): d¼1.38–1.41 (2H, m), 1.43–1.70 (8H, m), 3.91
(1H, dAB, JAB¼7.8 Hz, J¼6.9 Hz), 3.96(1H, ddd, J¼8.4, 3.9,
3.6 Hz), 4.05 (1H, dAB, JAB¼7.8 Hz, J¼6.6 Hz), 4.14 (1H,
ddd, J¼6.9, 6.6, 3.9 Hz), 4.26 (1H, dAB, JAB¼14.1 Hz,
J¼8.4 Hz), 4.37 (1H, dAB, JAB¼14.1 Hz, J¼3.6 Hz), 8.11
(1H, s), 8.19 (1H, s). 13C NMR (CD3OD): d¼25.03, 25.19,
26.47, 35.84, 37.02, 48.23, 66.25, 70.25, 77.67, 111.28,
119.90, 143.66, 150.77, 153.54, 157.18. Anal. calcd for
C15H21O3N5 (319.36): C, 56.41; H, 6.62; N, 21.93. Found: C,
56.56; H, 6.44; N, 21.78.
1
1365, 1097 cm21. H NMR (CDCl3): d¼1.30–1.40 (2H,
m), 1.50–1.65 (8H, m), 2.10–2.30 (1H, brs), 2.46 (3H, s),
3.68–3.83 (2H, m), 3.90 (1H, dAB, JAB¼12.7 Hz,
J¼3.6 Hz), 3.99 (1H, dd, J¼8.5, 6.3 Hz), 4.21 (1H, ddd,
J¼7.3, 6.3, 5.1 Hz), 4.52 (1H, ddd, J¼7.3, 4.4, 3.6 Hz),
7.26–7.38 and 7.79–7.84 (4H, m). 13C NMR (CDCl3):
d¼21.97, 23.93, 24.17, 25.27, 34.73, 36.36, 62.37, 66.21,
73.75, 82.39, 110.73, 127.94, 130.03, 133.43, 145.34.
4.1.13. (2R,3S)-3-O-Benzyl-1,2-O-cyclohexylidene-4-O-
(methanesulphonyl)butane-1,2,3,4-tetrol, (2R,3S)-23. To