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continued at 210 8C for 4 h. The reaction was decomposed
by addition of ice water. Pyridine was co evaporated with
toluene (2£3 mL). Chromatographic purification (10%
ethyl acetate/PE) gave a mixture of monomesyl derivatives
9a and 9b (1.10 g, 81%). The isomeric mixture was
dissolved in chloroform–hexane (30 mL, 1:1) and
refrigerated at 0 8C for 24 h to afford 9a (0.594 g, 44%) as
a white solid, mp 139–140 8C; [Found: C, 40.19; H, 6.33.
C10H18SO8 requires C, 40.26; H, 6.08]; Rf (60% ethyl
acetate/n-hexane) 0.22; [a]D¼253.3 (c 0.15, MeOH); nmax
(nujol) 3460–3200 (br), 1356 cm21; dH (300 MHz, D2O)
1.23 (3H, s, Me), 1.46 (3H, s, Me), 3.12 (3H, s, Me), 3.59
(2H, s, CH2OH), 4.19 (1H, br s, H3), 4.33 (2H, AB quartet,
J¼10.5 Hz, CH2OMs), 4.68 (1H, obscure with D2O signal,
H2) (confirmed by 1H–1H COSY experiments), 5.94 (1H, d,
J¼4.1 Hz, H1); dC (75 MHz, D2O) 24.8, 25.4, 36.5, 59.4,
67.8, 75.0, 86.7, 88.5, 104.9, 113.4. [For NOE experiment,
0.011 g of 9a was dissolved in 0.8 mL of D2O and the
solution was purged with N2 for 15 min].
as colourless needles, mp 94–95 8C; [Found: C, 55.58; H,
7.92. C12H20O6 requires C, 55.37; H, 7.74]; Rf (33% ethyl
acetate/n-hexane) 0.40; [a]D¼þ32.0 (c 0.25, CHCl3);
n
max(KBr) 3500–3410 (br) cm21; dH (300 MHz, CDCl3þ
D2O) 1.34 (3H, s, Me), 1.39 (3H, s, Me), 1.41 (3H, s, Me),
1.58 (3H, s, Me), 3.68 (1H, d, J¼12.1 Hz, OCH2), 3.70 (1H,
d, J¼11.5 Hz, OCH2), 3.86 (1H, d, J¼11.5 Hz, OCH2), 3.93
(1H, d, J¼12.1 Hz, OCH2), 4.14 (1H, s, H3), 4.64 (1H, d,
J¼4.1 Hz, H2), 6.06 (1H, d, J¼4.1 Hz, H1); dC (75 MHz,
CDCl3) 21.5, 25.5, 26.1, 26.3, 63.0, 63.8, 74.7, 85.4, 85.7,
99.1, 105.8, 112.2.
3.1.6. 1,2:5,50-Di-O-isopropylidene-4-C-(hydroxy-
methyl)-b-L-threo-pento-1,4-furanose (12). p-Toluene-
sulfonic acid (0.01 g, cat.) was added to a suspension of
triol 8 (0.4 g, 1.82 mmol) and 2,2-dimethoxypropane
(0.208 g, 1.99 mmol) in acetone (5 mL) at 20 8C. The
mixture became homogeneous after 5 min and tlc analysis
indicated that the reaction was complete. The solution was
concentrated, diluted with DCM (20 mL), washed with
saturated aqueous sodium bicarbonate solution (10 mL),
dried (Na2SO4) and concentrated. The crude product on
chromatography with 5% ethyl acetate/PE gave 11 (0.279 g,
59%). Further elution with 10% ethyl acetate/PE gave 12
(0.132 g, 28%) as a clear syrup; [Found: C, 55.66; H, 7.86.
C12H20O6 requires C, 55.37; H, 7.74]; Rf (33% ethyl acetate/
n-hexane) 0.39; [a]D¼210.7 (c 1.5, CHCl3); nmax (nujol)
3418 cm21; dH (300 MHz, CDCl3) 1.29 (3H, s, Me), 1.40
(3H, s, Me), 1.49 (3H, s, Me), 1.51 (3H, s, Me), 3.30–3.51
(1H, br s, exchange with D2O, OH), 3.74 (1H, d, J¼12.0 Hz,
OCH2), 3.91 (1H, d, J¼11.5 Hz, OCH2), 3.99 (1H, d,
J¼11.5 Hz, OCH2), 4.03 (1H, d, J¼12.0 Hz, OCH2), 4.52
(1H, s, H3), 4.60 (1H, d, J¼4.0 Hz, H2), 5.89 (1H, d,
J¼4.0 Hz, H1); dC (75 MHz, CDCl3) 19.3, 25.5, 26.4, 27.5,
61.7, 65.7, 75.3, 82.0, 86.7, 98.2, 105.0, 111.9.
3.1.4. (7S,8R,9S,9aR)-Octahydro-7-hydroxymethyl-
A
7,8,9-trihydroxy-2H-pyrido[1,2-a]pyrimidine (4).
solution of 9a (0.5 g, 1.67 mmol) in TFA–H2O (6 mL,
3:2) was stirred at 25 8C for 3 h. TFA was evaporated in
vacuo and co evaporated with water (2£2 mL). The
hemiacetal 10 thus obtained (0.398 g, 93%) was dissolved
in water (6 mL) and 1,3-diaminopropane (0.057 g,
0.769 mmol; 0.5 equiv.) was added carefully with stirring.
After 30 min a second lot of 1,3-diaminopropane (0.057 g,
0.5 equiv.) in MeOH (10 mL) was added dropwise at room
temperature. After 12 h amberlite A-21 anion exchange
resin (OH2 form, weak base) was added to neutralize
methanesulfonic acid. The solution was filtered and the
solvent was evaporated to give a gum that was dissolved in
ethanol (1 mL) and precipitated with diethyl ether (15 mL).
The precipitate thus obtained was filtered, washed with
diethyl ether and dried. Chromatographic purification of the
residue with chloroform/methanol/ammonia (80/19/1)
afforded 4 (0.272 g, 81%) as a hygroscopic semi-solid
mass; [Found: C, 35.25; H, 9.01. C9H18N2O4·5H2O requires
C, 35.06; H, 9.15]; Rf (66% methanol/chloroform) 0.14;
[a]D¼24.0 (c 0.5, MeOH); nmax (nujol) 3460–3150 (br),
2858 and 2735 cm21; dH (300 MHz, D2O) 1.62–1.78 (2H,
m, H3), 2.24 (1H, ddd, J¼11.4, 10.5, 4.1 Hz, H2a), 2.32
(1H, d, J¼3.2 Hz, H6a), 2.67 (1H, ddd, J¼12.3, 10.5,
4.3 Hz, H4a), 2.71 (1H, d, J¼13.2 Hz, H6e), 2.88 (1H, ddd,
J¼11.4, 3.8, 3.0 Hz, H2e), 2.95 (1H, d, J¼8.9 Hz, H9a),
3.17 (1H, br d, J¼12.3 Hz, H4e), 3.40 (1H, d, J¼9.6 Hz,
H8), 3.46 (2H, s, CH2OH), 3.49 (1H, dd, J¼9.8, 8.9 Hz,
H9); dC (75 MHz, D2O) 23.0, 42.9, 52.3, 57.6, 63.8, 71.0,
72.3, 72.4, 77.4.
3.1.7. 1,2:3,5-Di-O-isopropylidene-4-(S)-C-(methane-
sulfonyloxymethyl)-b-L-threo-pento-1,4-furanose (14).
To a solution of 11 (0.2 g, 0.77 mmol) in anhydrous
pyridine (0.5 mL) was added methanesulfonyl chloride
(0.106 g, 0.93 mmol) at 0 8C. The reaction mixture was
allowed to warm to room temperature and stirred for 4 h.
Usual work-up and chromatography (10% ethyl acetate/PE)
provided monomesylate 14 (0.24 g, 92%) as a white solid,
mp 99–100 8C; [Found: C, 46.23; H, 6.57. C13H22SO8
requires C, 46.14; H, 6.55]; Rf (25% ethyl acetate/n-hexane)
0.38; [a]D¼þ10.0 (c 0.2, CHCl3); nmax(KBr) 1352 cm21
;
dH (300 MHz, CDCl3) 1.34 ((3H, s, Me), 1.40 (3H, s, Me),
1.42 (3H, s, Me), 1.64 (3H, s, Me), 3.17 (3H, s, Me), 3.72
(1H, d, J¼12.6 Hz, OCH2), 3.98 (1H, d, J¼12.6 Hz, OCH2),
4.17 (1H, s, H3), 4.39 (1H, d, J¼11.1 Hz, CH2OMs), 4.53
(1H, d, J¼11.1 Hz, CH2OMs), 4.64 (1H, d, J¼3.8 Hz, H2),
6.09 (1H, d, J¼3.8 Hz, H1); dC (75 MHz, CDCl3) 21.0, 25.3,
26.0, 26.2, 38.1, 62.1, 69.7, 74.4, 82.9, 84.8, 99.0, 106.5,112.5.
3.1.5. 1,2:3,5-Di-O-isopropylidene-4-(R)-C-(hydroxy-
methyl)-b-L-threo-pento-1,4-furanose (11). To a suspen-
sion of triol 8 (0.5 g, 2.27 mmol) in methanol (10 mL) was
added 2,2-dimethoxypropane (0.380 g, 2.49 mmol)
followed by p-toluenesulfonic acid (0.01 g, cat.) at 20 8C.
The mixture became homogeneous after 5 min and tlc
analysis indicated that the reaction was complete. The
solution was concentrated, diluted with DCM (20 mL),
washed with saturated aqueous sodium bicarbonate solution
(10 mL), dried (Na2SO4) and concentrated. Chromato-
graphy with 5% ethyl acetate/PE gave 11 (0.524 g, 89%)
3.1.8. (7R,8R,9S,9aR)-Octahydro-7-hydroxymethyl-
A
7,8,9-trihydroxy-2H-pyrido[1,2-a]pyrimidine (5).
solution of 14 (0.135 g, 0.326 mmol) in TFA-H2O (4 mL,
3:2) was stirred for 3 h. TFA was evaporated under vacuum
and co evaporated with water (3£2 mL) to leave a
hemiacetal 15 (0.106 g, 97%). The hemiacetal 15
(0.105 g, 0.314 mmol) was dissolved in water (3 mL) and
1,3-diaminopropane (0.012 g, 0.161 mmol) (0.5 equiv.) was