R. Roy, J. M. Kim / Tetrahedron 59 (2003) 3881–3893
3889
The above triflate was dissolved in DMF (20 mL) and
sodium benzoate (5.78 g, 0.040 mmol) was added. The
reaction mixture remained heterogeneous and was stirred at
room temperature for 20 h. The reaction mixture was diluted
with CHCl3 (30 mL) and washed thoroughly and succes-
sively with brine (2£30 mL) and water (3£30 mL). The
organic phase was dried over anhydrous Na2SO4 and
concentrated. Purification of the crude product by silica
gel chromatography eluting with 7:3 EtOAc/Hexanes
foam;[a]D¼þ50.2 (c 1.1, CHCl3); 1H NMR (CDCl3) d
1.94, 1.98, 2.03, 2.14 (4 s, 12H, OAc, NAc), 3.33 (ddd, 1H,
Jd,c¼13.5 Hz, Jd,b¼2.9 Hz, Jd,a¼5.5 Hz, H-d), 3.52 (ddd,
1H, Jc,d¼13.5 Hz, Jc,a¼3.0 Hz, Jc,b¼8.0 Hz, H-c), 3.65
(ddd, 1H, Jb,a¼10.8 Hz, Jb,c¼8.0 Hz, Jb,d¼2.9 Hz, H-b),
3.89 (ddd, 1H, Ja,b¼10.8 Hz, Ja,c¼3.0 Hz, Ja,d¼5.5 Hz,
H-a), 4.05–4.12 (m, 2H, H-60s), 4.16 (dt, 1H, J5,6¼6.9 Hz,
J4,5¼1.0 Hz, H-5), 4.60 (ddd, 1H, J2,3¼11.4 Hz,
J2,NH¼9.6 Hz, H-2), 4.93 (d, 1H, J1,2¼3.6 Hz, H-1), 5.16
(dd, 1H, J2,3¼11.4 Hz, J3,4¼3.3 Hz, H-3), 5.38 (dd, 1H,
J3,4¼3.3 Hz, H4,5 1.1 Hz, H-4), 5.64 (d, 1H, NH); 13C NMR
(CDCl3) d 20.6 (OAc), 23.1 (NAc), 47.4 (C-2), 50.3 (CH2),
61.8 (C-6), 66.9 (CH2), 67.2 (C-3), 674 (C-4), 68.0 (C-5),
97.9 (C-1), 170.1, 170.2, 170.3, 170.8 (CvO’s); CI-MS
(m/z) calcd for C16H24N4O9: 416.15; found: 417.0 (Mþþ1,
91.0%). Anal. calcd C, 46.14; H, 5.81; N, 13.46; found:
46.21; H, 5.85; N, 13.40.
1
yielded 3 (3.07 g, 64%) as a white foam; triflate H NMR
(CDCl3) d 1.83 (s, 3H, NAc), 3.35–3.46 (m, 1H, CHaN3),
3.52–3.77 (m, 2H, OCHcCHbN3), 3.90–4.02 (m, 1H,
OCHd), 4.30–4.47 (m, 2H, H-60, H-5), 4.58 (ddd, 1H,
0
J2,3¼10.8 Hz, J2,NH¼9.6 Hz, H-2), 4.81 (dd, 1H, J6,5
¼
11.9 Hz, J5,6¼1.4 Hz, H-6), 4.96 (d, 1H, J1,2¼3.5 Hz, H-1),
5.33 (dd, 1H, J3,4¼9.7 Hz, H-3), 5.75 (dd, 1H,
J4,5¼10.7 Hz, H-4), 5.92 (d, 1H, NH), 7.40–7.66 (m, 6H,
Armeta, Arpara), 8.04, 8.09 (2dd, Jo,m¼6.6 Hz, Jo,p¼1.2 Hz,
Arortho); FAB-MS (pos. m/z) calcd for C25H25N4O10SF3:
630.12; found: 631.19 (Mþþ1, 25.2%); 3: [a]D¼þ103.3 (c
4.1.7. 2-Aminoethyl 2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-a-D-galactopyranoside hydrochloride (5). To a
solution of 2-azidoethyl 2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-a-D-galactopyranoside (4) (1.0 g, 2.40 mmol) in
MeOH (100 mL) was added 10% Pd/C (0.20 g) and acetic
acid (0.14 g, 2.40 mmol). The heterogeneous solution was
bubbled with H2 gas for 24 h. The reaction mixture was
filtered through a celite pad and the filtrate was gently
stirred with Amberlite IRA (Cl2) resin (2.0 g) for 24 h. The
resin was filtered off and the filtrate was concentrated to
provide 5 (0.97 g, 95%) as a white foam; 1H NMR (CDCl3)
d 1.94, 1.99, 2.01, 2.11 (4s, 12H, OAc, NAc), 3.27 (bs, 2H,
CH2N), 3.64–3.73 (m, 3H, OCHH, NH2), 3.90–4.08 (m,
3H, OCHH, H-60s), 4.28 (dd, 1H, J5,6¼6.0 Hz, H-5), 4.53
(ddd, 1H, J2,NH¼9.4 Hz, J2,3¼11.3 Hz, H-2), 4.91 (d, 1H,
J1,2¼3.3 Hz, H-1), 5.27 (dd, 1H, J3,4¼3.1 Hz, H-3), 5.35 (d,
1H, H-4), 7.67 (d, 1H, NH); 13C NMR (CDCl3) d 20.6
(OAc), 22.8 (NAc), 39.3 (CH2), 47.0 (C-2), 62.0 (C-6), 63.5
(CH2), 66.9 (C-3), 67.1 (C-4), 68.2 (C-5), 98.1 (C-1), 170.4,
170.4, 171.0, 171.2 (CvO’s); FAB-MS (pos. m/z) calcd for
C16H26N2O9: 390.16; found: 391.23 (Mþþ1, 98.4%).
1
1.0, CHCl3); H NMR (CDCl3) d 1.84 (s, 3H, NAc), 3.33
(ddd, 1H, Ja,b¼13.4 Hz, Ja,d¼5.5 Hz, Ja,c¼2.9 Hz, CHaHb-
N3), 3.50 (ddd, 1H, Jb,a¼13.4 Hz, Jb,c¼7.9 Hz, Jb,d¼3.0 Hz,
CHaHbN3), 3.69 (ddd, 1H, Jc,d¼10.7 Hz, Jc,b¼7.9 Hz,
Jc,a¼2.9 Hz, OCHcHd), 3.95 (ddd, 1H, Jd,c¼10.7 Hz,
Jd,a¼5.5 Hz, Jd,b¼3.0 Hz, OCHcHd), 4.37 (dd, 1H,
0
0
0
J6,6 ¼9.8 Hz, J5,6 ¼4.3 Hz, H-6 ), 4.51–4.57 (m, 2H, H-5,
H-6), 4.94 (ddd, 1H, J2,3¼11.3 Hz, J2,NH¼9.5 Hz, H-2),
5.12 (d, 1H, J1,2¼3.5 Hz, H-1), 5.57 (dd, 1H, J3,4¼3.3 Hz,
H-3), 5.92 (d, 1H, H-4), 6.01 (d, 1H, NH), 7.25, 7.36 (2t, 4H,
Armeta), 7.43 (t, 3H, Arpara, Armeta), 7.49, 7.56 (2t, 2H,
Jm,p¼7.4 Hz, Arpara), 7.80, 7.96, 8.06 (3d, 6H, Jo,m¼7.3 Hz,
Arortho); 13C NMR (CDCl3) d 23.15 (CH3), 48.21 (C-2), 50.
43 (CH2), 62.53 (C-6), 67.50 (CH2), 67.60 (C-3), 68.25
(C-4), 69.03 (C-5), 98.20 (C-1), 128.37, 128.42, 128.62
(Armeta’s), 128.84, 129.07, 129.37 (Aripso’s), 129.63,
129.83, 129.94 (Arortho’s), 133.24, 133.38, 133.55
(Arpara’s), 165.71, 166.00, 166.39, 170.43 (CvO’s); FAB-
MS (pos. m/z) calcd for C31H30N4O9: 602.20; found: 603.19
(Mþþ1, 2.0%). Anal. calcd for: C, 61.79; H, 5.02; Found:
C, 61.77; H, 4.95.
4.1.8. N-Boc-6-aminocaproic acid. 1-Aminocaproic acid
(1.2 g, 9.15 mmol) and NaOH (0.73 g, 18.3 mmol) were
dissolved in water (5 mL). A solution of di-t-butyl
dicarbonate (2.0 g, 9.15 mmol) in CH2Cl2 (15 mL) was
added to the aqueous solution at 08C and stirred at room
temperature for 48 h. The progress of the reaction was
monitored by ninhydrin test. When the reaction was
complete, the solution was acidified by adding conc. HCl
dropwise. The organic layer was separated from the aqueous
layer, which was then extracted with CHCl3 (2£20 mL).
The combined organic phase was dried over anhydrous
Na2SO4 and then concentrated. Purification of the crude
product by silica gel chromatography eluting with 18:1:1
CHCl3/CH3CN/CH3OH yielded 1.94 g (92%) of a colorless
oil which physical data corresponded to those published;19
1H NMR (CDCl3) d 1.32 (quintet, 2H, J¼6.7 Hz, H-e), 1.39
(s, 9H, t-Bu), 1.45 (quintet, 2H, J¼7.4 Hz, H-f), 1.59
(quintet, 2H, J¼7.6 Hz, H-d), 2.29 (t, 2H, J¼7.4 Hz, H-c),
3.05 (t, 2H, J¼6.8 Hz, H-g), 4.59 (bs, 1H, NH), 10.3 (bs,
1H, CO2H); 13C NMR (CDCl3) d 24.3 (C-d), 26.1 (C-e),
28.3 (t-Bu), 29.6 (C-f), 33.9 (C-c), 40.2 (C-g), 79.1 (CMe3),
156.0, 178.9 (CvO’s); CI-MS (m/z) calcd for C22H21NO4:
231.1; found: 232.0 (Mþþ1, 2.3 %).
4.1.6. 2-Azidoethyl 2-acetamido-3,4,6-tri-O-acetyl-2-
deoxy-a-D-galactopyranoside (4). 2-Azidoethyl 2-aceta-
mido-3,4,6-tri-O-benzoyl-2-deoxy-a-D-galactopyranoside
(3) (8.5 g, 17.1 mmol) was dissolved in MeOH (100 mL)
and 1 M sodium methoxide was added dropwise until the
pH of the solution reached ,9.0. The solution was stirred at
room temperature for 3 h. When the reaction was complete,
the solution was treated with Amberlite IR (H) resin for
15 min. to neutralize the base. The resin was filtered off and
the filtrate was concentrated to dryness to provide the de-O-
acetylated compound.
The dried residue was dissolved in pyridine (20 mL) and
acetic anhydride (15 mL) was added. The solution was
stirred at room temperature for 16 h and then concentrated
under reduced pressure. The residue was dissolved in CHCl3
(30 mL) and washed with 5% aqueous HCl (2£20 mL),
saturated NaHCO3 (2£20 mL), water (1£20 mL), then dried
over anhydrous Na2SO4. Purification of the crude product
by silica gel chromatography eluting with 4:1 EtOAc/
Hexanes yielded
4
(6.05 g, 85%) as
a
white