3.39 (1H, dd, J6Ј,5 7.9 Hz, HЈ-6), 3.78 (1H, m, H-5), 3.97 (1H,
dd, J4,3 8.2 Hz, J4,5 3.0 Hz, H-4), 4.07 (1H, a-dt, J3,OH 5.9 Hz,
H-3), 4.26 (1H, dd, J2,3 8.9 Hz, J2,OH 6.7 Hz, H-2), 5.66 (1H,
d, OH-2/OH-5), 5.86 (1H, d, OH-3), 6.09 (1H, d, OH-5/OH-2);
δC (d6-DMSO): 53.0 (t, C-6), 67.8, 72.9, 73.9, 80.3 (4 × d,
7.51; N, 14.37. C12H21O5N3 requires: C, 50.17; H, 7.37; N,
14.63%); [α]D23 ϩ59.9 (c, 0.82 in CHCl3); νmax (thin film): 3448
(OH), 2102 (N3) cmϪ1; δH (CDCl3): 1.37, 1.39, 1.40, 1.46 (12H,
4 × s, 2 × C(CH3)2), 2.32 (1H, br s, OH), 3.33 (1H, dd, J6,5 5.2
Hz, J6,6Ј 13.2 Hz, H-6), 3.68 (1H, dd, J6Ј,5 2.7 Hz, HЈ-6), 3.73–
3.85 (4H, m, H-1, H-1Ј, H-3, H-4), 4.05 (1H, m, J4,5 7.7 Hz,
H-2), 4.14 (1H, ddd, H-5); δC (CDCl3): 26.8, 26.9 (2 × q,
2 × C(CH3)2), 51.7, 62.3 (2 × t, C-1, C-6), 78.0, 78.7, 80.1, 81.2
(4 × d, C-2, C-3, C-4, C-5), 109.9, 110.5 (2 × s, 2 × C(CH3)2);
m/z (APCI ϩ ve): 260.2 (M Ϫ N2 ϩ Hϩ, 100%).
C-2, C-3, C-4, C-5), 174.6 (s, C᎐O); m/z (APCI Ϫ ve): 202.0
᎐
(M Ϫ Hϩ, 100%).
6-Amino-6-deoxy-D-galactono-1,6-lactam 21
A solution of the azido lactone 22 (1.03 g, 5.07 mmol) in
methanol (50 ml) was stirred under an atmosphere of hydrogen
in the presence of palladium black (70 mg). After 48 h, TLC
(ethyl acetate) indicated complete conversion of the starting
material (Rf 0.5) to a major product (Rf 0.0). The reaction mix-
ture was filtered through Celite (eluted with MeOH and H2O)
and the solvent removed in vacuo. The residue was dissolved in
hot methanol, filtered and the solvent removed in vacuo to give
the ε-lactam 21 (794 mg, 90%) as an off white solid (Found: C,
40.51; H, 6.14; N, 7.63. C6H11O5N requires: C, 40.68; H, 6.26;
N, 7.91%); mp 175–176 ЊC (foam) [lit.,10 mp 175–177 ЊC
(foam)]; [α]D25 Ϫ16.3 (c, 1.00 in H2O) [lit.,10 [α]D20 Ϫ22.0 (c, 1.30 in
6-Azido-6-deoxy-2,3:4,5-di-O-isopropylidene-1-O-methyl-
sulfonyl-D-galactitol 23
Methanesulfonyl chloride (66 µl, 0.85 mmol) was added to a
stirred solution of the azido alcohol 19 (204 mg, 0.71 mmol)
and 4-dimethylaminopyridine (4 mg, catalytic) in pyridine (4
ml) at 0 ЊC, under an atmosphere of nitrogen. After 2.5 h, TLC
(ethyl acetate–hexanes 1:2) indicated complete conversion of
the starting material (Rf 0.2) to a single product (Rf 0.25). The
solvent was removed in vacuo (co-evaporated with toluene) and
the residue dissolved in dichloromethane (50 ml) and washed
with water (20 ml) and brine (10 ml). The organic phase was
dried (MgSO4), filtered and concentrated in vacuo. The residue
was purified by flash chromatography (ethyl acetate–hexanes
1:2) to give the azido mesylate 23 (259 mg, 100%) as an
amorphous solid (Found: C, 42.64; H, 6.30; N, 11.29. C13H23-
O7N3S requires: C, 42.73; H, 6.34; N, 11.50%); [α]D23 ϩ32.8 (c,
1.33 in CHCl3); νmax (thin film): 2103 (N3) cmϪ1; δH (CDCl3):
1.43, 1.44, 1.47, 1.51 (12H, 4 × s, 2 × C(CH3)2), 3.13 (3H, s,
SO2CH3), 3.38 (1H, dd, J6,5 5.0 Hz, J6,6Ј 13.2 Hz, H-6), 3.74 (1H,
dd, J6Ј,5 2.7 Hz, HЈ-6), 3.85 (2H, m, H-3, H-4), 4.19 (1H, ddd,
J5,4 Hz, H-5), 4.26 (1H, ddd, H-2), 4.38 (1H, dd, J1,1Ј 11.3 Hz,
J1,2 5.4 Hz, H-1), 4.58 (1H, dd, J1Ј,2 2.3 Hz, HЈ-1); δC (CDCl3):
25.8, 26.9 (2 × q, 2 × C(CH3)2), 37.7 (q, SO2CH3), 51.6, 68.8
(2 × t, C-1, C-6), 77.4, 78.0, 78.7, 80.0 (4 × d, C-2, C-3, C-4,
C-5), 110.7, 110.9 (2 × s, 2 × C(CH3)2); m/z (APCI ϩ ve): 338.1
(M Ϫ N2 ϩ Hϩ, 100%).
H2O)]; νmax (thin film): 1660 (C᎐O, lactam) cmϪ1; δH (d6-DMSO,
᎐
COSY): 2.99 (1H, br s, H-6), 3.34 (1H, br s, HЈ-6), 3.52 (2H, m,
H-3, H-5), 3.69 (1H, br s, H-4), 4.20 (1H, m, H-2), 4.53 (2H, br
s, OH-2, OH-5), 4.92 (2H, br s, OH-3, OH-4), 7.71 (1H, br s,
NH); δC (D2O, 50.3 MHz): 41.0 (t, C-6), 69.5, 73.7 (2 × d, C-2,
C-3, C-4, C-5), 176.8 (s, C᎐O); m/z (APCI-ve): 178.0 (M ϩ Hϩ,
᎐
100%).
6-Amino-6-deoxy-3,4-O-isopropylidene-D-galactono-1,6-lactam
24
Toluene-p-sulfonic acid monohydrate (10 mg, catalytic) was
added to a stirred suspension of the unprotected lactam 21 (118
mg, 0.67 mmol) in 2,2-dimethoxypropane (1 ml) and acetone
(4 ml). The reaction mixture was stirred at 80 ЊC for 3 h, under
an atmosphere of nitrogen. TLC (ethyl acetate–methanol 4:1)
indicated complete conversion of starting material (Rf 0.25) to a
major product (Rf 0.45). Sodium carbonate (200 mg) was added
to neutralise the mixture which was then filtered through Celite.
The solvent was removed in vacuo and the residue purified by
flash chromatography (ethyl acetate–methanol 19:1 to 9:1) to
yield the lactam monoacetonide 24 (96 mg, 66%) as a white
crystalline solid (Found: C, 49.66; H, 7.08; N, 6.33. C9H15O5N
requires: C, 49.76; H, 6.96; N, 6.45%); mp 168 ЊC (ethyl acetate–
methanol); [α]D23 ϩ10.8 (c, 0.48 in MeOH); νmax (thin film): 3436
Methyl 2,5-anhydro-6-azido-6-deoxy-D-talonate 27 and methyl
2,5-anhydro-6-azido-6-deoxy-L-allonate 33
Trifluoromethanesulfonic anhydride (2.83 ml, 16.8 mmol) was
added to a stirred solution of the azido lactone 22 (2.27 g, 11.2
mmol) in anhydrous ethyl acetate (80 ml) and dry pyridine (4.53
ml, 56.0 mmol) at Ϫ10 ЊC, under an atmosphere of nitrogen.
The reaction mixture was stirred at Ϫ10 ЊC for 15 min. TLC
(ethyl acetate–hexanes 3:1) indicated complete conversion of
the starting material (Rf 0.3) to a major product (Rf 0.8).
Methanol (160 ml) was added and the reaction mixture allowed
to warm to room temperature and stirred for 40 h. TLC (ethyl
acetate–hexanes 3:1) indicated conversion of the triflate (Rf 0.8)
to a major product (Rf 0.3). The solvent was removed in vacuo
(co-evaporation with toluene) and the residue preadsorbed
onto silica and purified by flash chromatography (ethyl acetate–
hexanes 1:1 to 2:1) to yield an inseparable mixture of methyl
-talonate 27 and methyl -allonate 33 (1.12 g, 46%) as a
colourless oil (HRMS Ϫ N2 ϩ Hϩ: 190.071801. C7H11O5N3 Ϫ
N2 ϩ Hϩ requires: 190.071548); νmax (thin film): 3436 (OH),
2107 (N ), 1740 (C᎐O, ester) cmϪ1; δH (CD3OD), methyl
(OH, NH), 1640 (C᎐O, lactam) cmϪ1; δH (D2O): 1.38, 1.40 (6H,
᎐
2 × s, C(CH3)2), 3.16 (1H, dd, J6,5 5.3 Hz, J6,6Ј 15.9 Hz, H-6),
3.62 (1H, a-d, H-6’), 3.83 (1H, a-t, H-5), 4.12 (1H, dd, J3,2 9.8
Hz, J3,4 2.3 Hz, H-3), 4.15 (1H, a-t, H-4), 4.87 (1H, d, H-2);
δC (D2O): 25.2, 25.7 (2 × q, C(CH3)2), 39.7 (t, C-6), 68.2, 68.3,
71.6, 75.1 (4 × d, C-2, C-3, C-4, C-5), 111.4 (s, C(CH3)2), 173.8
(s, C᎐O); m/z (APCI ϩ ve): 218.1 (M Ϫ Hϩ, 100%).
᎐
6-Azido-6-deoxy-2,3:4,5-di-O-isopropylidene-D-galactitol 19
Lithium borohydride (0.86 ml, 2 M in THF) was added to a
solution of the azido ester 18 (544 mg, 1.73 mmol) in THF (10
ml) at 0 ЊC. The reaction mixture was allowed to warm to room
temperature and stirred for 10 h, under an atmosphere of nitro-
gen. TLC (ethyl acetate–hexanes 1:1) indicated complete con-
version of the starting material (Rf 0.7) to a major product (Rf
0.45). Saturated ammonium chloride solution (2 ml) was added
and the mixture diluted with ethyl acetate (30 ml) and washed
with saturated ammonium chloride solution (2 × 10 ml) and
brine (20 ml). The organic phase was dried (MgSO4), filtered
and concentrated in vacuo. The residue was purified by flash
chromatography (ethyl acetate–hexanes 1:2) to yield the azido
alcohol 19 (397 mg, 80%) as a colourless oil which solidified
upon standing to an amorphous solid (Found: C, 50.23; H,
᎐
3
-talonate 27: 3.48 (2H, a-d, H-6, HЈ-6), 3.76 (3H, s, CO2CH3),
4.14 (1H, a-t, H-4), 4.22 (1H, m, H-5), 4.28–4.32 (2H, m, H-2,
H-3); δH (CD3OD) methyl -allonate 33: 3.41 (1H, dd, J6,5 6.0
Hz, J6,6Ј 13.2 Hz, H-6), 3.48 (1H, dd, JJ6Ј,5 3.2 Hz, HЈ-6), 3.75
(3H, s, CO2CH3), 3.94 (1H, dd, J4,3 5.0 Hz, J4,5 6.6 Hz, H-4),
4.01 (1H, m, H-5), 4.19 (1H, dd, J3,2 3.4 Hz, H-3), 4.36 (1H, d,
H-2); δC (CD3OD, 50.3 MHz) methyl -talonate 27: 50.2 (t,
C-6), 51.4 (q, CO2CH3), 71.5, 75.8, 80.3, 80.6 (4 × d, C-2, C-3,
C-4, C-5), 173.2 (s, C᎐O), δ (CD3OD, 50.3 MHz) methyl
᎐
C
-allonate 33: 51.4 (q, CO2CH3), 52.2 (t, C-6), 72.3, 74.2, 82.3,
82.5 (4 × d, C-2, C-3, C-4, C-5), 171.9 (s, C᎐O); m/z
᎐
J. Chem. Soc., Perkin Trans. 1, 1999, 901–908
907