1908
P. Alle6i et al. / Tetrahedron: Asymmetry 13 (2002) 1901–1910
32.2 [ring-N: CH2CH(NHCbz)CO2But], 30.2 (N+
CH2CH2), 27.8 [3×C(CH3)3 and ring-5: CH2CH-
(NHCbz)CO2But], 26.1 [ring-5: CH2CH2CH(NHCbz)-
CO2But], 22.0 [ring-N: CH2CH2CH(NHCbz)CO2But].
Anal. calcd for C54H70N4O13: C, 65.97; H, 7.18; N,
5.70. Found: C, 65.82; H, 7.23; N, 5.66%.
156.2, 141.5 and 141.2 (C-3, C-4 and C-5 pyridinium
ring), 135.3 and 129.0 (C-2 and C-6 pyridinium ring),
61.1 (N+CH2−CH2), 54.5, 54.2 and 53.0 [3×
+
CH(NH3 )CO2 ], 30.7, 30.0, 29.8, 27.9, 25.6 and 25.6.
1H and 13C NMR spectra are in agreement with the
literature data;4,5b,7c ESI/MS m/z 413 (M+). Anal. calcd
for C18H34Cl4N4O8: C, 37.51; H, 5.95; N, 9.72; Cl,
24.61. Found: C, 37.66; H, 6.02; N, 9.88; Cl, 24.25%.
The obtained benzyloxycarbonyl derivative (400 mg,
0.41 mmol), dissolved in MeOH (90 mL), was hydro-
genated in the presence of 10% Pd/C (70 mg) for 12 h
at room temperature and atmospheric pressure. Filtra
tion of the catalyst on a pad of Celite and evaporation
of the solvent under reduced pressure afforded the
4-[(S)-2-amino-2-(tert-butyloxycarbonyl)ethyl]-5-[(S)-
3 - amino - 3 - (tert - butyloxycarbonyl)propyl] - 1 - [(S) - 5-
amino-5-(tert-butyloxycarbonyl)pentyl]-3-pyridiniumo-
late (215 mg, 90%) as an resinous material: [h]2D0 +32.8
3.15. 4-[(S)-2-Benzyloxycarbonylamino-2-(tert-butyloxy-
carbonyl)ethyl]-5-[(S)-3-benzyloxycarbonylamino-3-(tert-
butyloxycarbonyl)propyl]-1-[(2R,5S)-5-benzyloxycarbonyl
amino-5-(allyloxycarbonyl)-2-hydroxypentyl]-3-pyri-
diniumolate, 24
A solution of 4-[(S)-2-benzyloxycarbonylamino-2-(tert-
butyloxycarbonyl)ethyl] - 5 - [(S) - 3 - benzyloxycarbonyl-
amino - 3 - (tert - butyloxycarbonyl)propyl] - 3 - hydroxy-
pyridine 236c (265 mg, 0.4 mmol) and allyl (2S,5R)-2-
benzyloxycarbonylamino-5-hydroxy-6-iodohexanoate
20 (714 mg, 1.6 mmol) in CH3CN (5 mL) was heated
under reflux for 16 h under an argon atmosphere. The
solvent was then evaporated under reduced pressure to
give a crude product whose UV spectrum (in MeOH)
shows umax at 296 nm indicating (unpublished results
from our laboratory) the presence of the 3-hydroxypyri-
dinium iodide form of the alkylated compound.
1
(c 1, CHCl3) (lit.5b +32.5); H NMR (CD3OD): l 7.57
(1H, br s, pyridinium-H), 7.48 (1H, br s, pyridinium-
H), 4.34 (2H, t, J=7.3, N+CH2CH2), 4.20 [1H, dd,
J=7.3 and 3.0, ring-4: CH(NH2)CO2But], 3.73 [1H, m,
ring-5: CH(NH2)CO2But], 3.64 [1H, m, ring-N:
CH(NH2)CO2But], 3.33 [1H, m, ring-4: CHHCH-
(NH2)CO2But], 3.20 [1H, m, ring-4: CHHCH(NH2)-
CO2But], 2.91 [1H, m, ring-5: CHHCH2CH(NH2)-
CO2But], 2.81 [1H, m, ring-5: CHHCH2CH(NH2)-
CO2But], 2.07–1.78 (6H, overlapping), 1.52, 1.48 and
1.38 [3×9H, 3×s, 3×C(CH3)3], 1.40–1.28 (2H, N+
CH2CH2CH2 masked by But signals); 13C NMR
(CD3OD): l 172.7, 171.1 and 169.5 (3×CO2But), 168.2,
142.5 and 141.4 (C-3, C-4 and C-5 pyridinium ring),
132.4 and 128.6 (C-2 and C-6 pyridinium ring), 85.1,
84.5 and 84.0 [3×C(CH3)3], 61.3 (N+CH2CH2), 54.8,
54.5 and 53.7 [3×CH(NH2)CO2But], 34.6 [ring-5:
CH2CH(NH2)CO2But], 32.1, 31.9 and 29.9 [ring-4:
CH2CH(NH2)CO2But, ring-N: CH2CH(NH2)CO2But,
ring-5: CH2CH2CH(NH2)CO2But and N+CH2CH2]
28.2 [3×C(CH3)3], 23.1 [N+CH2CH2CH2].
This crude product was chromatographed (eluting first
with AcOEt and then with AcOEt–MeOH; 100:7 v/v)
to afford, in order, the excess iodohydrin 20 (445 mg),
the starting pyridine 23 (16 mg) and then the title
compound 24 (247 mg, 63%): a resinous material which
resisted all efforts of crystallisation. Its UV spectrum
(in MeOH) shows umax at 231, 260 and 336 nm and thus
indicates that it is in the 3-pyridiniumolate form (a
zwitterion) supported also by an appropriate elemental
1
analysis; [h]D=−2.3 (c 0.6, CHCl3); H NMR (CDCl3–
D2O): l 7.39 (1H, br s, pyridinium-H), 7.35–7.20 (15H,
aromatics-H), 6.95 (1H, br s, pyridinium-H), 5.85 (1H,
dddd, J=16.8, 10.52, 5.0, 5.0, CH2ꢀCH-CH2O), 5.29
(1H, dd, J=16.8, <1, CHHꢀCH-CH2O),), 5.20 (1H,
dd, J=10.52 and <1, CHHꢀCH-CH2O), 5.10–5.05 (4H,
overlapping, 2×OCH2Ph), 5.00 (1H, d, J=12.6, A part
of AB system, OCHHPh), 4.90 (1H, J=12.6, B part of
AB system, OCHHPh), 4.60 (2H, m, CH2ꢀCH-CH2O),
4.68 [1H, dd, J=7.0 and 5.6, ring-N: CH(N-
HCbz)CO2Allyl], 4.24 [1H, dd, J=9.8 and 3.5, ring-4:
CH(NHCbz)CO2But], 4.19 [1H, dd, 7.0, 4.9, ring-5:
CH(NHCbz)CO2But], 3.87–3.81 [2H, overlapping, N+
CHHCH(OH) and N+CH2CH(OH)], 3.69 [1H, dd, J=
13.3 and 7.5, N+CHHCH(OH)], 3.62 [1H, dd, J=13.3
and 9.8, ring-4: CHHCH(NHCbz)CO2But], 3.26 [1H,
dd, J=13.3 and 3.5, ring-4: CHHCH(NHCbz)CO2But],
2.72–2.63 [2H, m, ring-5: CH2CH2CH(NHCbz)-
CO2But], 2.08–1.95 [2H, overlapping, ring-5: CHHCH-
(NHCbz)CO2But and ring-N: CHHCH(NHCbz)CO2-
Allyl], 1.84 [1H, m, ring-5: CHHCH(NHCbz)CO2But],
1.77 [1H, m, ring-N: CHHCH(NHCbz)CO2Allyl], 1.51
[1H, m, N+CH2CH(OH)CHH], 1.44 and 1.36 [2×9H,
2×s, 2×C(CH3)3], 1.7–1.12 [N+CH2CH(OH)CHH
masked by But signals]. 13C NMR (CDCl3): l 171.8,
The obtained tert-butyl derivative (204 mg, 0.35 mmol)
was dissolved in CF3CO2H–H2O (8 mL, 95:5, v/v) and
the resulting solution was stirred at room temperature
for 40 min. The solvent was then removed under
reduced pressure and the residue was purified by
column chromatography (eluting with MeOH–NH3;
80:20 v/v). The product obtained was dissolved in
aqueous HCl (4.0 mL, 1.0 M) and the solution was
lyophilised to afford the deoxypyridinoline 2 as the
hydrochloride monohydrate (141 mg, 70%): [h]2D0 +33.4
(c 1, H2O)) [lit. +32.16a (c 0.9, H2O) +31.67c (c 0.25,
1
MeOH); +36.28b (c 0.535, MeOH)]; H NMR (D2O): l
8.19 (1H, br s, pyridinium-H), 8.13 (1H, br s, pyri-
dinium-H), 4.43 (2H, t, J=7.2, N+CH2CH2), 4.05 [1H,
t, J=7.2, ring-4: CH(NH3 )COO−], 3.82 [1H, t, J=5.5,
+
ring-5: CH(NH3 )COO−], 3.70 [1H, t, J=5.7, ring-N:
+
CH(NH3 )COO−], 3.34–3.26 [2H, m, ring-4: CH2CH-
+
(NH3+)COO−], 2.93 [1H, m, ring-5: CHHCH2CH-
+
(NH3+)COO−], 2.82 [1H, m, ring-5: CHHCH2CH-
(NH3 )COO−], 2.12 [2H, m, ring-5: CH2CH(NH3 )-
+
COO−], 1.98 (2H, ddt, J=7.2, 7.2 and 7.0, N+CH2CH2),
1.84 [2H, m, ring-N: CH2CH(NH3 )COO−], 1.42 (1H,
+
m, N+CH2CH2CHH), 1.34 (1H, m, N+CH2CH2CHH);
13C NMR (D2O): l 174.4, 173.8, and 172.8 (3×CO2 ),
−